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Sample records for acute ischemia-reperfusion model

  1. A novel laser-Doppler flowmetry assisted murine model of acute hindlimb ischemia-reperfusion for free flap research.

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    Tolga Taha Sönmez

    Full Text Available Suitable and reproducible experimental models of translational research in reconstructive surgery that allow in-vivo investigation of diverse molecular and cellular mechanisms are still limited. To this end we created a novel murine model of acute hindlimb ischemia-reperfusion to mimic a microsurgical free flap procedure. Thirty-six C57BL6 mice (n = 6/group were assigned to one control and five experimental groups (subject to 6, 12, 96, 120 hours and 14 days of reperfusion, respectively following 4 hours of complete hindlimb ischemia. Ischemia and reperfusion were monitored using Laser-Doppler Flowmetry. Hindlimb tissue components (skin and muscle were investigated using histopathology, quantitative immunohistochemistry and immunofluorescence. Despite massive initial tissue damage induced by ischemia-reperfusion injury, the structure of the skin component was restored after 96 hours. During the same time, muscle cells were replaced by young myotubes. In addition, initial neuromuscular dysfunction, edema and swelling resolved by day 4. After two weeks, no functional or neuromuscular deficits were detectable. Furthermore, upregulation of VEGF and tissue infiltration with CD34-positive stem cells led to new capillary formation, which peaked with significantly higher values after two weeks. These data indicate that our model is suitable to investigate cellular and molecular tissue alterations from ischemia-reperfusion such as occur during free flap procedures.

  2. Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

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    Nathalie Le Clef

    Full Text Available Acute kidney injury (AKI is an underestimated, yet important risk factor for development of chronic kidney disease (CKD. Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD. Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data.

  3. Unilateral Renal Ischemia-Reperfusion as a Robust Model for Acute to Chronic Kidney Injury in Mice.

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    Le Clef, Nathalie; Verhulst, Anja; D'Haese, Patrick C; Vervaet, Benjamin A

    2016-01-01

    Acute kidney injury (AKI) is an underestimated, yet important risk factor for development of chronic kidney disease (CKD). Even after initial total recovery of renal function, some patients develop progressive and persistent deterioration of renal function and these patients are more likely to progress to end-stage renal disease (ESRD). Animal models are indispensable for unravelling the mechanisms underlying this progression towards CKD and ESRD and for the development of new therapeutic strategies in its prevention or treatment. Ischemia (i.e. hypoperfusion after surgery, bleeding, dehydration, shock, or sepsis) is a major aetiology in human AKI, yet unilateral ischemia-reperfusion is a rarely used animal model for research on CKD and fibrosis. Here, we demonstrate in C57Bl/6J mice, by both histology and gene expression, that unilateral ischemia-reperfusion without contralateral nephrectomy is a very robust model to study the progression from acute renal injury to long-term tubulo-interstitial fibrosis, i.e. the histopathological hallmark of CKD. Furthermore, we report that the extent of renal fibrosis, in terms of Col I, TGFβ, CCN2 and CCN3 expression and collagen I immunostaining, increases with increasing body temperature during ischemia and ischemia-time. Thus, varying these two main determinants of ischemic injury allows tuning the extent of the long-term fibrotic outcome in this model. Finally, in order to cover the whole practical finesse of ischemia-reperfusion and allow model and data transfer, we provide a referenced overview on crucial technical issues (incl. anaesthesia, analgesia, and pre- and post-operative care) with the specific aim of putting starters in the right direction of implementing ischemia in their research and stimulate them, as well as the community, to have a critical view on ischemic literature data.

  4. Acute ischemia/reperfusion injury after isogeneic kidney transplantation is mitigated in a rat model of chronic renal failure.

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    Vercauteren, Sven R; Ysebaert, Dirk K; Van Rompay, An R; De Greef, Kathleen E; De Broe, Marc E

    2003-05-01

    The influence of chronic renal failure on renal susceptibility to an acute ischemic insult was evaluated. Recipient Lewis rats were randomly assigned to undergo 5/6 nephrectomy (chronic renal failure, CRF) or sham operation (normal renal function, NRF). After 11 weeks, normal kidneys of Lewis donor rats were transplanted in the recipients. The outcome of the isografts was assessed. Filtration capacity of the isografts in the CRF rats was preserved to approximately one-quarter of its normal capacity on the 1st day post-transplantation, whereas it fell to 0 in the NRF rats. This was reflected by a significantly higher increase in serum creatinine in the latter group. The isografts in the CRF rats had a significantly lower degree of acute tubular necrosis and no increase in the number of macrophages and T lymphocytes in the first 24 h in contrast to the NRF rats. Epithelial regeneration and repair started earlier in the CRF group. In conclusion, the present study indicated that CRF blunted ischemia/reperfusion injury of a transplanted kidney, and that its regeneration capacity was certainly not hampered by the presence of chronic uremia. These results will be the basis for studies on modulation of early leukocyte-endothelial interactions resulting from immunological disturbances inherent to the uremic environment.

  5. Intravenous Administration of Cilostazol Nanoparticles Ameliorates Acute Ischemic Stroke in a Cerebral Ischemia/Reperfusion-Induced Injury Model

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    Noriaki Nagai

    2015-12-01

    Full Text Available It was reported that cilostazol (CLZ suppressed disruption of the microvasculature in ischemic areas. In this study, we have designed novel injection formulations containing CLZ nanoparticles using 0.5% methylcellulose, 0.2% docusate sodium salt, and mill methods (CLZnano dispersion; particle size 81 ± 59 nm, mean ± S.D., and investigated their toxicity and usefulness in a cerebral ischemia/reperfusion-induced injury model (MCAO/reperfusion mice. The pharmacokinetics of injections of CLZnano dispersions is similar to that of CLZ solutions prepared with 2-hydroxypropyl-β-cyclodextrin, and no changes in the rate of hemolysis of rabbit red blood cells, a model of cell injury, were observed with CLZnano dispersions. In addition, the intravenous injection of 0.6 mg/kg CLZnano dispersions does not affect the blood pressure and blood flow, and the 0.6 mg/kg CLZnano dispersions ameliorate neurological deficits and ischemic stroke in MCAO/reperfusion mice. It is possible that the CLZnano dispersions will provide effective therapy for ischemic stroke patients, and that injection preparations of lipophilic drugs containing drug nanoparticles expand their therapeutic usage.

  6. Establishment and Evaluation of Rat Acute Kidney Ischemia/Reperfusion Model%大鼠急性肾缺血再灌注损伤模型的建立与评估

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    易小敏; 张更; 马帅军; 刘克普; 袁建林

    2011-01-01

    目的:对现有的经腹部切口建立急性肾缺血再灌注损伤动物模型进行改良,探索建立急性肾缺血再灌注损伤模型的新方法.方法:实验组大鼠16例,经背部切口进入腹膜后间隙,游离钳夹双侧肾动脉45 min后开放血流,建立急性肾缺血再灌注损伤模型;伪手术组8例,不夹闭肾动脉,余步骤与实验组相同;对照组8例无处理.术后通过建模成功率、组织病理检查、血肌酐和血尿素氮及氧化应激水平对模型进行评估.结果:实验组l5只成功建立急性肾缺血再灌注损伤模型.术后l天病理检查显示实验组肾组织出现广泛损伤,术后实验组肾小管坏死评分、肾MDA水平、血肌酐及血尿素氮值明显高于对照组(P<0.05).结论:经背部切口钳夹双侧肾动脉可建立稳定的大鼠急性肾缺血再灌注损伤模型.该造模方法简便易行,成功率高,且具备手术切口小、手术时间短及并发症少的优点,建立的模型适合于急性肾损伤的研究.%Objective: To improve current acute kidney ischemia/reperfusion animal model through abdominal incision and investigate a new approach to establish acute kidney ischemia/reperfusion animal model. Methods: Acute rat kidney ischemia/reperfusion model was established by dorsal incision by clamping bilateral renal arteries for 45 min in experimental group (n=16); The same procedure without renal artery clamping was implemented in sham operating group (n=8); No treatment was given to control group (n=8). Established model was assessed by histopathological examining, concentrations of serum creatinine and blood urea nitrogen, and oxidative stress in kidney and success ratio of acute kidney ischemia/reperfusion model establishment. Results: Acute kidney ischemia/reperfusion model was established successfully. There were extensive injuries in experimental group, while kidney morphostructure appeared normal in control group. Tubular injury score, MDA level

  7. Recovery of renal function after administration of adipose-tissue-derived stromal vascular fraction in rat model of acute kidney injury induced by ischemia/reperfusion injury.

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    Lee, Chunwoo; Jang, Myoung Jin; Kim, Bo Hyun; Park, Jin Young; You, Dalsan; Jeong, In Gab; Hong, Jun Hyuk; Kim, Choung-Soo

    2017-03-10

    Acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) injury is a major challenge in critical care medicine. The purpose of this study is to determine the therapeutic effects of the adipose-tissue-derived stromal vascular fraction (SVF) and the optimal route for SVF delivery in a rat model of AKI induced by I/R injury. Fifty male Sprague-Dawley rats were randomly divided into five groups (10 animals per group): sham, nephrectomy control, I/R injury control, renal arterial SVF infusion and subcapsular SVF injection. To induce AKI by I/R injury, the left renal artery was clamped with a nontraumatic vascular clamp for 40 min, and the right kidney was removed. Rats receiving renal arterial infusion of SVF had a significantly reduced increase in serum creatinine compared with the I/R injury control group at 4 days after I/R injury. The glomerular filtration rate of the renal arterial SVF infusion group was maintained at a level similar to that of the sham and nephrectomy control groups at 14 days after I/R injury. Masson's trichrome staining showed significantly less fibrosis in the renal arterial SVF infusion group compared with that in the I/R injury control group in the outer stripe (P renal arterial SVF infusion and subcapsular SVF injection groups compared with the I/R injury control group in the outer stripe (P renal function is effectively rescued from AKI induced by I/R injury through the renal arterial administration of SVF in a rat model.

  8. Thymoquinone protects end organs from abdominal aorta ischemia/reperfusion injury in a rat model

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    Mehmet Salih Aydin

    2015-02-01

    Full Text Available Introduction: Previous studies have demonstrated that thymoquinone has protective effects against ischemia reperfusion injury to various organs like lungs, kidneys and liver in different experimental models. Objective: We aimed to determine whether thymoquinone has favorable effects on lung, renal, heart tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury. Methods: Thirty rats were divided into three groups as sham (n=10, control (n=10 and thymoquinone (TQ treatment group (n=10. Control and TQ-treatment groups underwent abdominal aorta ischemia for 45 minutes followed by a 120-min period of reperfusion. In the TQ-treatment group, thymoquinone was given 5 minutes. before reperfusion at a dose of 20 mg/kg via an intraperitoneal route. Total antioxidant capacity, total oxidative status (TOS, and oxidative stress index (OSI in blood serum were measured and lung, kidney, and heart tissue histopathology were evaluated with light microscopy. Results: Total oxidative status and oxidative stress index activity in blood samples were statistically higher in the control group compared to the sham and TQ-treatment groups (P<0.001 for TOS and OSI. Control group injury scores were statistically higher compared to sham and TQ-treatment groups (P<0.001 for all comparisons. Conclusion: Thymoquinone administered intraperitoneally was effective in reducing oxidative stress and histopathologic injury in an acute abdominal aorta ischemia-reperfusion rat model.

  9. Evaluation of stem cell administration in a model of kidney ischemia-reperfusion injury.

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    da Silva, Léa Bueno Lucas; Palma, Patrícia Viana Bonini; Cury, Patrícia Maluf; Bueno, Valquiria

    2007-12-15

    Ischemia-reperfusion injury is a common early event in kidney transplantation and contributes to a delay in organ function. Acute tubular necrosis, impaired kidney function and organ leukocyte infiltration are the major findings. The therapeutic potential of stem cells has been the focus of recent research as these cells possess capabilities such as self-renewal, multipotent differentiation and aid in regeneration after organ injury. FTY720 is a new synthetic compound that has been associated with preferential migration of blood lymphocytes to peripheral lymph nodes instead of inflammatory sites. Bone marrow stem cells (BMSC) and/or FTY720 were used as therapy to promote recovery of tubule cells and avoid inflammation at the renal site, respectively. Mice were submitted to renal ischemia-reperfusion injury and were either treated with two doses of FTY720, 10x10(6) BMSC, or both in order to compare the therapeutic effect with non-treated and control animals. Renal function and structure were investigated as were cell numbers in peripheral blood and spleen. Activation and apoptosis markers were also evaluated in splenocytes using flow cytometry. We found that the combined therapy (FTY720+BMSC) was associated with more significant changes in renal function and structure after ischemia-reperfusion injury when compared with the other groups. Also a decrease at cell numbers and prevention of spleen cells activation and apoptosis was observed. In conclusion, in our model it was not possible to demonstrate the potential of stem cells alone or in combination with FTY720 to promote early kidney recovery after ischemia-reperfusion injury.

  10. [Preventive effects of troxipide on a newly developed model of acute gastric mucosal lesion (AGML) induced by ischemia/reperfusion plus ammonia in the rat].

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    Momo, K; Hoshina, K; Ishibashi, Y; Saito, T

    1994-10-01

    We have developed a unique rat AGML model produced by ischemia/reperfusion plus 0.2% ammonia (I/R.NH3), either treatment which would not induce mucosal injury when used alone. The effects of troxipide and other gastric mucosal defensive drugs were investigated with this I/R.NH3-induced AGML model and other AGML models in rats. The following results were obtained: 1) Like allopurinol, troxipide at 50-200 mg/kg, p.o. dose-dependently prevented I/R.NH3-induced development of AGML and also the ischemia/reperfusion-induced increase of gastric mucosal thiobarbituric acid (TBA)-reactive substances; 2) Troxipide at 10(-6)-10(-4) M, like allopurinol, inhibited concentration-dependently in vitro xanthine oxidase activity in gastric mucosal homogenates; 3) Troxipide at 50-200 mg/kg, p.o. inhibited AGMLs induced by bleeding plus 0.2% ammonia and by 1.0% ammonia alone; and 4) Troxipide and sofalcone were similar in preventing all AGMLs tested and also the increase of mucosal TBA-reactive substances, but somewhat differed from teprenone, cetraxate hydrochloride, azulene plus L-glutamine and sucralfate. These findings suggest that troxipide may inhibit I/R.NH3-induced AGML development by preventing generation of oxygen free radicals and by protecting against mucosal fragility due to reduced energy metabolism from poor blood flow and also against ammonia-induced disruption of the gastric mucosal barrier. Therefore, troxipide may be highly effective for various AGMLs with multifactor involvement.

  11. Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury

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    Chen, Lijuan [Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Wang, Yingjie [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Internal Medicine of Traditional Chinese Medicine, Shuguang Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Pan, Yaohua; Zhang, Lan [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Shen, Chengxing [Department of Cardiology, Xinhua Hospital, Shanghai Jiao Tong University, Shanghai (China); Qin, Gangjian [Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 (United States); Ashraf, Muhammad [Pathology and Lab Med, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Weintraub, Neal [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States); Ma, Genshan, E-mail: magenshan@hotmail.com [Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009 (China); Tang, Yaoliang, E-mail: tangyg@ucmail.uc.edu [Cardiovascular Disease, Internal Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267 (United States)

    2013-02-15

    Highlights: ► Cardiac progenitor-derived (CPC) Exosomes protect H9C2 from apoptosis in vitro. ► CPC-exosomes protect cardiomyoyctes from MI/R induced apoptosis in vivo. ► CPC-exosomes were taken up by H9C2 with high efficiency using PKH26 labeling. ► miR-451, one of GATA4-responsive miRNA cluster, is enriched in CPC-exosomes. -- Abstract: Background: Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. Methods and results: CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC-exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 h incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation invitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control (p < 0.05). Conclusion: Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.

  12. Effect of total flavonoids of Radix Ilicis pubescentis on cerebral ischemia reperfusion model

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    Xiaoli Yan

    2017-03-01

    Full Text Available This paper aims to observe the effects of total flavonoids of Radix Ilicis pubescentis on mouse model of cerebral ischemia reperfusion. Mice were orally given different doses of total flavonoids of Radix Ilicis pubescentis 10 d, and were administered once daily. On the tenth day after the administration of 1 h in mice after anesthesia, we used needle to hook the bilateral common carotid artery (CCA for 10 min, with 10 min ischemia reperfusion, 10 min ischemia. Then we restored their blood supply, copy the model of cerebral ischemia reperfusion; We then had all mice reperfused for 24 h, and then took their orbital blood samples and measured blood rheology. We quickly removed the brain, with half of the brain having sagittal incision. Then we fixed the brains and sectioned them to observe the pathological changes of brain cells in the hippocampus and cortex. We also measured the other half sample which was made of brain homogenate of NO, NOS, Na+-K+-, ATP enzyme Mg2+-ATPase and Ca2+-ATPase. Acupuncture needle hook occlusion of bilateral common carotid arteries can successfully establish the model of cerebral ischemia reperfusion. After comparing with the model mice, we concluded that Ilex pubescens flavonoids not only reduce damage to the brain nerve cells in the hippocampus and cortex, but also significantly reduce the content of NO in brain homogenate, the activity of nitric oxide synthase (NOS and increases ATP enzyme activity (P < 0.05, P < 0.01. In this way, cerebral ischemia reperfusion injury is improved. Different dosages of Ilex pubescens flavonoids on mouse cerebral ischemia reperfusion model have good effects.

  13. Role of interleukin 18 in acute lung inflammation induced by gut ischemia reperfusion

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    Yong-Jie Yang; Yun Shen; Song-Hua Chen; Xi-Rui Ge

    2005-01-01

    AIM: To study the changes of endogenous interleukin 18 (IL-18) levels and evaluate the role of IL-18 on lung injury following gut ischemia/reperfusion.METHODS: A superior mesenteric artery occlusion model was selected for this research. The mice were randomly divided into four groups: Sham operation (sham), ischemia (0.5 h) followed by different times of reperfusion (I/R),and I/R pretreated with exogenous IL-18 (I/R+IL-18) or IL-18 neutralizing antibody (I/R+IL-18Ab) 15 min before ischemia. Serum IL-18 levels were detected by Western blot and ELISA, and the levels of IL-18 in lung tissue were evaluated by immunohistochemical staining. For the study of pulmonary inflammation, the lung myeloperoxidase (MPO) contents and morphological changes were evaluated.RESULTS: Gut ischemia/reperfusion induced rapid increase of serum IL-18 levels, peaked at 1 h after reperfusion and then declined. The levels of IL-18 in lung tissue were gradually enhanced as the progress of reperfusion.Compared with I/R group, exogenous administration of IL-18 (I/R+IL-18) further remarkably enhanced the pulmonary MPO activity and inflammatory cell infiltration,and in I/R+IL-18Ab group, the content of MPO were significantly reduced and lung inflammation was also decreased.CONCLUSION: Gut ischemia/reperfusion induces the increase of IL-18 expression, which may make IL-18 act as an important proinflammatory cytokine and contribute to gut ischemia/reperfusion-induced lung inflammation.

  14. Pretreatment with low doses of acenocoumarol inhibits the development of acute ischemia/reperfusion-induced pancreatitis.

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    Warzecha, Z; Sendur, P; Ceranowicz, P; Dembinski, M; Cieszkowski, J; Kusnierz-Cabala, B; Tomaszewska, R; Dembinski, A

    2015-10-01

    Coagulative disorders are known to occur in acute pancreatitis and are related to the severity of this disease. Various experimental and clinical studies have shown protective and therapeutic effect of heparin in acute pancreatitis. Aim of the present study was to determine the influence of acenocoumarol, a vitamin K antagonist, on the development of acute pancreatitis. Studies were performed on male Wistar rats weighing 250 - 270 g. Acenocoumarol at the dose of 50, 100 or 150 μg/kg/dose or vehicle were administered once a day for 7 days before induction of acute pancreatitis. Acute pancreatitis was induced in rats by pancreatic ischemia followed by reperfusion. The severity of acute pancreatitis was assessed after 5-h reperfusion. Pretreatment with acenocoumarol given at the dose of 50 or 100 μg/kg/dose reduced morphological signs of acute pancreatitis. These effects were accompanied with a decrease in the pancreatitis-evoked increase in serum activity of lipase and serum concentration of pro-inflammatory interleukin-1β. Moreover, the pancreatitis-evoked reductions in pancreatic DNA synthesis and pancreatic blood flow were partially reversed by pretreatment with acenocoumarol given at the dose of 50 and 100 μg/kg/dose. Administration of acenocoumarol at the dose of 150 μg/kg/dose did not exhibit any protective effect against ischemia/reperfusion-induced pancreatitis. We concluded that pretreatment with low doses of acenocoumarol reduces the severity of ischemia/reperfusion-induced acute pancreatitis.

  15. Tramadol Alleviates Myocardial Injury Induced by Acute Hindlimb Ischemia Reperfusion in Rats

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    Hamed Ashrafzadeh Takhtfooladi

    2015-01-01

    Full Text Available Background: Organ injury occurs not only during periods of ischemia but also during reperfusion. It is known that ischemia reperfusion (IR causes both remote organ and local injuries. Objective: This study evaluated the effects of tramadol on the heart as a remote organ after acute hindlimb IR. Methods: Thirty healthy mature male Wistar rats were allocated randomly into three groups: Group I (sham, Group II (IR, and Group III (IR + tramadol. Ischemia was induced in anesthetized rats by left femoral artery clamping for 3 h, followed by 3 h of reperfusion. Tramadol (20 mg/kg, intravenous was administered immediately prior to reperfusion. At the end of the reperfusion, animals were euthanized, and hearts were harvested for histological and biochemical examination. Results: The levels of superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GPx were higher in Groups I and III than those in Group II (p < 0.05. In comparison with other groups, tissue malondialdehyde (MDA levels in Group II were significantly increased (p < 0.05, and this increase was prevented by tramadol. Histopathological changes, including microscopic bleeding, edema, neutrophil infiltration, and necrosis, were scored. The total injuryscore in Group III was significantly decreased (p < 0.05 compared with Group II. Conclusion: From the histological and biochemical perspectives, treatment with tramadol alleviated the myocardial injuries induced by skeletal muscle IR in this experimental model.

  16. Tramadol Alleviates Myocardial Injury Induced by Acute Hindlimb Ischemia Reperfusion in Rats

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    Takhtfooladi, Hamed Ashrafzadeh; Asl, Adel Haghighi Khiabanian [Department of Pathobiology, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Shahzamani, Mehran [Department of Cardiovascular Surgery, Isfahan University of Medical Sciences, Tehran (Iran, Islamic Republic of); Takhtfooladi, Mohammad Ashrafzadeh, E-mail: dr-ashrafzadeh@yahoo.com [Young Researchers and Elites Club, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Allahverdi, Amin [Department of Surgery, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Khansari, Mohammadreza [Department of Physiology, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of)

    2015-08-15

    Organ injury occurs not only during periods of ischemia but also during reperfusion. It is known that ischemia reperfusion (IR) causes both remote organ and local injuries. This study evaluated the effects of tramadol on the heart as a remote organ after acute hindlimb IR. Thirty healthy mature male Wistar rats were allocated randomly into three groups: Group I (sham), Group II (IR), and Group III (IR + tramadol). Ischemia was induced in anesthetized rats by left femoral artery clamping for 3 h, followed by 3 h of reperfusion. Tramadol (20 mg/kg, intravenous) was administered immediately prior to reperfusion. At the end of the reperfusion, animals were euthanized, and hearts were harvested for histological and biochemical examination. The levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were higher in Groups I and III than those in Group II (p < 0.05). In comparison with other groups, tissue malondialdehyde (MDA) levels in Group II were significantly increased (p < 0.05), and this increase was prevented by tramadol. Histopathological changes, including microscopic bleeding, edema, neutrophil infiltration, and necrosis, were scored. The total injuryscore in Group III was significantly decreased (p < 0.05) compared with Group II. From the histological and biochemical perspectives, treatment with tramadol alleviated the myocardial injuries induced by skeletal muscle IR in this experimental model.

  17. Protective Effect of N-Acetylserotonin against Acute Hepatic Ischemia-Reperfusion Injury in Mice

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    Jiying Jiang

    2013-08-01

    Full Text Available The purpose of this study was to investigate the possible protective effect of N-acetylserotonin (NAS against acute hepatic ischemia-reperfusion (I/R injury in mice. Adult male mice were randomly divided into three groups: sham, I/R, and I/R + NAS. The hepatic I/R injury model was generated by clamping the hepatic artery, portal vein, and common bile duct with a microvascular bulldog clamp for 30 min, and then removing the clamp and allowing reperfusion for 6 h. Morphologic changes and hepatocyte apoptosis were evaluated by hematoxylin-eosin (HE and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining, respectively. Activated caspase-3 expression was evaluated by immunohistochemistry and Western blot. The activation of aspartate aminotransferase (AST, malondialdehyde (MDA, and superoxide dismutase (SOD was evaluated by enzyme-linked immunosorbent assay (ELISA. The data show that NAS rescued hepatocyte morphological damage and dysfunction, decreased the number of apoptotic hepatocytes, and reduced caspase-3 activation. Our work demonstrates that NAS ameliorates hepatic IR injury.

  18. Sustained protective effects of 7-monohydroxyethylrutoside in an in vivo model of cardiac ischemia-reperfusion

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    De Celle, T; Heeringa, P; Strzelecka, AE; Bast, A; Smits, JF; Janssen, BJ

    2004-01-01

    Earlier studies have shown that 7-monohydroxyethylrutoside (monoHER), an antioxidant flavonoid, protects against doxorubicin-induced cardiotoxicity. In this study, we investigated potential sustained cardioprotective effects of monoHER in a model of ischemia-reperfusion (I/R) in mice. Ischemia was i

  19. The Protective Effects of Curcumin on Experimental Acute Liver Lesion Induced by Intestinal Ischemia-Reperfusion through Inhibiting the Pathway of NF-κB in a Rat Model

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    Zhe Fan

    2014-01-01

    Full Text Available Objective. In this study, we investigated the protective effect and mechanism of curcumin on a rat model of intestinal ischemia/reperfusion (I/R, which induces an acute liver lesion. Methods. Curcumin was injected into rats in the curcumin groups through left femoral vein. The same volume of vehicle (0.9% normal saline was injected into sham and I/R groups. Blood and liver tissue were gathered for serological and histopathological determination. Results. Intestinal I/R led to severe liver injury manifested as a significant increase in serum AST and ALT levels; all of those were reduced by treatment with curcumin. Simultaneously, the activity of SOD in liver decreased after intestinal I/R, which was increased by curcumin treatment. On the other hand, curcumin reduced MPO activity of liver tissue, as well as serum IL-6 and TNF-α levels observably. This is in parallel with the decreased level of liver intercellular cell adhesion molecule-1 (ICAM-1 and nuclear factor-κB (NF-κB expression. Conclusion. Our findings suggest that curcumin treatment attenuates liver lesion induced by intestinal I/R, attributable to the antioxidative and anti-inflammatory effect via inhibition of the NF-κB pathway.

  20. Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    Na Zhang; Gen-Yang Cheng; Xian-Zhi Liu; Feng-Jiang Zhang

    2014-01-01

    Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue. Methods:Fourty eight rats were randomly divided into four groups(n=12): sham operation group,30 min ischemia60 min reperfusion group,60 min ischemia60 min reperfusion group, and 120 min ischemia60 min reperfusion group.The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreasedBcl-2 expression, increasedBax expression, upregulated expression ofNF-κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation.

  1. Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

    Science.gov (United States)

    la Garza, Francisco Javier Guzmán-de; Ibarra-Hernández, Juan Manuel; Cordero-Pérez, Paula; Villegas-Quintero, Pablo; Villarreal-Ovalle, Claudia Ivette; Torres-González, Liliana; Oliva-Sosa, Norma Edith; Alarcón-Galván, Gabriela; Fernández-Garza, Nancy Esthela; Muñoz-Espinosa, Linda Elsa; Cámara-Lemarroy, Carlos Rodrigo; Carrillo-Arriaga, José Gerardo

    2013-01-01

    OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion. PMID:23917671

  2. Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

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    Francisco Javier Guzmán-de la Garza

    2013-07-01

    Full Text Available OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student’s t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion.

  3. Obestatin Accelerates the Recovery in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

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    Jakub Bukowczan

    Full Text Available Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis, and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration following the onset of experimental acute pancreatitis.The aim of this study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. Moreover, we tested the influence of ischemia/reperfusion-induced acute pancreatitis and administration of obestatin on daily food intake and pancreatic exocrine secretion.Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8 nmol/kg/dose was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. Secretory studies were performed on the third day after sham-operation or induction of acute pancreatitis in conscious rats equipped with chronic pancreatic fistula.Treatment with obestatin ameliorated morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland, and led to earlier pancreatic regeneration. Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1β level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow. Induction of acute pancreatitis by pancreatic ischemia followed by reperfusion significantly decreased daily food intake and

  4. A Translational Study of a New Therapeutic Approach for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin into Reperfused Myocardium Reduces Ischemia-Reperfusion Injury in a Preclinical Porcine Model

    Science.gov (United States)

    Ichimura, Kenzo; Matoba, Tetsuya; Nakano, Kaku; Tokutome, Masaki; Honda, Katsuya; Koga, Jun-ichiro; Egashira, Kensuke

    2016-01-01

    Background There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction, for which interventional reperfusion therapy is hampered by ischemia-reperfusion (IR) injury. We recently reported that bioabsorbable poly(lactic acid/glycolic acid) (PLGA) nanoparticle-mediated treatment with pitavastatin (pitavastatin-NP) exerts a cardioprotective effect in a rat IR injury model by activating the PI3K-Akt pathway and inhibiting inflammation. To obtain preclinical proof-of-concept evidence, in this study, we examined the effect of pitavastatin-NP on myocardial IR injury in conscious and anesthetized pig models. Methods and Results Eighty-four Bama mini-pigs were surgically implanted with a pneumatic cuff occluder at the left circumflex coronary artery (LCx) and telemetry transmitters to continuously monitor electrocardiogram as well as to monitor arterial blood pressure and heart rate. The LCx was occluded for 60 minutes, followed by 24 hours of reperfusion under conscious conditions. Intravenous administration of pitavastatin-NP containing ≥ 8 mg/body of pitavastatin 5 minutes before reperfusion significantly reduced infarct size; by contrast, pitavastatin alone (8 mg/body) showed no therapeutic effects. Pitavastatin-NP produced anti-apoptotic effects on cultured cardiomyocytes in vitro. Cardiac magnetic resonance imaging performed 4 weeks after IR injury revealed that pitavastatin-NP reduced the extent of left ventricle remodeling. Importantly, pitavastatin-NP exerted no significant effects on blood pressure, heart rate, or serum biochemistry. Exploratory examinations in anesthetized pigs showed pharmacokinetic analysis and the effects of pitavastatin-NP on no-reflow phenomenon. Conclusions NP-mediated delivery of pitavastatin to IR-injured myocardium exerts cardioprotective effects on IR injury without apparent adverse side effects in a preclinical conscious pig model. Thus, pitavastatin-NP represents a novel therapeutic

  5. Combination of tadalafil and diltiazem attenuates renal ischemia reperfusion-induced acute renal failure in rats.

    Science.gov (United States)

    El-Sisi, Alaa E; Sokar, Samia S; Abu-Risha, Sally E; Ibrahim, Hanaa A

    2016-12-01

    Life threatening conditions characterized by renal ischemia/reperfusion (RIR) such as kidney transplantation, partial nephrectomy, renal artery angioplasty, cardiopulmonary bypass and aortic bypass surgery, continue to be among the most frequent causes of acute renal failure. The current study investigated the possible protective effects of tadalafil alone and in combination with diltiazem in experimentally-induced renal ischemia/reperfusion injury in rats. Possible underlying mechanisms were also investigated such as oxidative stress and inflammation. Rats were divided into sham-operated and I/R-operated groups. Anesthetized rats (urethane 1.3g/kg) were subjected to bilateral ischemia for 30min by occlusion of renal pedicles, then reperfused for 6h. Rats in the vehicle I/R group showed a significant (p˂0.05) increase in kidney malondialdehyde (MDA) content; myeloperoxidase (MPO) activity; TNF-α and IL-1β contents. In addition significant (p˂0.05) increase in intercellular adhesion molecule-1(ICAM-1) content, BUN and creatinine levels, along with significant decrease in kidney superoxide dismutase (SOD) activity. In addition, marked diffuse histopathological damage and severe cytoplasmic staining of caspase-3 were detected. Pretreatment with combination of tadalafil (5mg/kg bdwt) and diltiazem (5mg/kg bdwt) resulted in reversal of the increased biochemical parameters investigated. Also, histopathological examination revealed partial return to normal cellular architecture. In conclusion, pretreatment with tadalafil and diltiazem combination protected against RIR injury.

  6. Partial hexokinase II knockout results in acute ischemia-reperfusion damage in skeletal muscle of male, but not female, mice

    NARCIS (Netherlands)

    Smeele, K.M.; Eerbeek, O.; Koeman, A.; Bezemer, R.; Ince, C.; Heikkinen, S.; Laakso, M.; de Haan, A.; Schaart, G.; Drost, M.R.; Hollmann, M.W.; Zuurbier, C.J.

    2010-01-01

    Cellular studies have demonstrated a protective role of mitochondrial hexokinase against oxidative insults. It is unknown whether HK protective effects translate to the in vivo condition. In the present study, we hypothesize that HK affects acute ischemia-reperfusion injury in skeletal muscle of the

  7. Extracellular ascorbic acid fluctuation during the protective process of ischemic preconditioning in rabbit renal ischemia-reperfusion model measured

    Institute of Scientific and Technical Information of China (English)

    LIU Lei; LIN Yu-qing; YAN Long-tao; HONG Kai; HOU Xiao-fei; MAO Lan-qun; MA Lu-lin

    2010-01-01

    Background Ascorbic acid has important antioxidant properties, and may play a role in the protective effects of ischemic preconditioning on later ischemia-reperfusion. Herein, we examined the role of endogenous extracellular ascorbic acid in ischemic preconditioning in the kidney.Methods We developed a solitary rabbit kidney model where animals received ischemia-reperfusion only (ischemia-reperfusion group, n=15) or ischemic preconditioning followed by ischemia-reperfusion (ischemic preconditioning group, n=15). Ischemia-reperfusion was induced by occluding and loosening of the renal pedicle. The process of ischemic preconditioning included 15-minute brief ischemia and 10-minute reperfusion. In vivo microdialysis coupled with online electrochemical detection was used to determine levels of endogenous extracellular ascorbic acid in both groups. The extent of tissue damage was determined in kidney sections stained with hematoxylin and eosin. Serum creatinine and urea nitrogen were also detected to assess renal function.Results During ischemia-reperfusion, the extracellular ascorbic acid concentration during ischemia increased rapidly to the peak level ((130.01 ±9.98)%), and then decreased slowly to near basal levels. Similar changes were observed during reperfusion (peak level, (126.78±18.24)%). In the ischemic preconditioning group there was a similar pattern of extracellular ascorbic acid concentration during ischemic preconditioning. However, the ascorbic acid level was significantly lower during the ischemia and early reperfusion stage compared to the ischemia-reperfusion group. Additionally, the extent of glomerular ischemic collapse, tubular dilation, tubular denudation, and loss of brush border were markedly attenuated in the ischemic preconditioning group. Levels of serum creatinine and urea nitrogen were also decreased significantly in the ischemic preconditioning group.Conclusions Ischemic preconditioning may protect renal tissue against ischemia-reperfusion

  8. A New Therapeutic Modality for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin Induces Cardioprotection from Ischemia-Reperfusion Injury via Activation of PI3K/Akt Pathway and Anti-Inflammation in a Rat Model.

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    Kazuhiro Nagaoka

    Full Text Available There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction (AMI, for which the effectiveness of interventional reperfusion therapy is hampered by myocardial ischemia-reperfusion (IR injury. Pretreatment with statins before ischemia is shown to reduce MI size in animals. However, no benefit was found in animals and patients with AMI when administered at the time of reperfusion, suggesting insufficient drug targeting into the IR myocardium. Here we tested the hypothesis that nanoparticle-mediated targeting of pitavastatin protects the heart from IR injury.In a rat IR model, poly(lactic acid/glycolic acid (PLGA nanoparticle incorporating FITC accumulated in the IR myocardium through enhanced vascular permeability, and in CD11b-positive leukocytes in the IR myocardium and peripheral blood after intravenous treatment. Intravenous treatment with PLGA nanoparticle containing pitavastatin (Pitavastatin-NP, 1 mg/kg at reperfusion reduced MI size after 24 hours and ameliorated left ventricular dysfunction 4-week after reperfusion; by contrast, pitavastatin alone (as high as 10 mg/kg showed no therapeutic effects. The therapeutic effects of Pitavastatin-NP were blunted by a PI3K inhibitor wortmannin, but not by a mitochondrial permeability transition pore inhibitor cyclosporine A. Pitavastatin-NP induced phosphorylation of Akt and GSK3β, and inhibited inflammation and cardiomyocyte apoptosis in the IR myocardium.Nanoparticle-mediated targeting of pitavastatin induced cardioprotection from IR injury by activation of PI3K/Akt pathway and inhibition of inflammation and cardiomyocyte death in this model. This strategy can be developed as an innovative cardioprotective modality that may advance currently unsatisfactory reperfusion therapy for AMI.

  9. Magnetic Resonance Imaging (MRI) Analysis of Ischemia/Reperfusion in Experimental Acute Renal Injury.

    Science.gov (United States)

    Pohlmann, Andreas; Arakelyan, Karen; Seeliger, Erdmann; Niendorf, Thoralf

    2016-01-01

    Imbalance between renal oxygen delivery and demand in the first hours after reperfusion is suggested to be decisive in the pathophysiological chain of events leading to ischemia-induced acute kidney injury. Here we describe blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) for continuous monitoring of the deoxyhemoglobin-sensitive MR parameter T 2* in the renal cortex, outer medulla, and inner medulla of rats throughout renal ischemia/reperfusion (I/R). Changes during I/R are benchmarked against the effects of variations in the fraction of inspired oxygen (hypoxia, hyperoxia). This method may be useful for investigating renal blood oxygenation of rats in vivo under various experimental (patho)physiological conditions.

  10. Salvianolate increases heat shock protein expression in a cerebral ischemia-reperfusion injury model

    Institute of Scientific and Technical Information of China (English)

    Jinnan Zhang; Wei Lu; Qiang Lei; Xi Tao; Hong You; Pinghui Xie

    2013-01-01

    Stroke remains a worldwide health problem. Salvianolate exerts a protective effect in various mi-crocirculatory disturbance-related diseases, but studies of the mechanisms underlying its protective action have mainly focused on the myocardium, whereas little research has been carried out in brain tissue fol owing ischemia-reperfusion. We assessed the neuroprotective effects of salvianolate in a rat model of cerebral ischemia-reperfusion injury induced using the suture method. At onset and 24 and 48 hours after reperfusion, rats were intraperitoneal y injected with salvianolate (18 mg/kg) or saline. Neurological deficit scores at 72 hours showed that the neurological functions of rats that had received salvianolate were significantly better than those of the rats that had received saline. 2,3,5-Triphenyltetrazolium chloride was used to stain cerebral tissue to determine the extent of the infarct area. A significantly smal er infarct area and a significantly lower number of apoptotic cel s were observed after treatment with salvianolate compared with the saline treatment. Expression of heat shock protein 22 and phosphorylated protein kinase B in ischemic brain tissue was significantly greater in rats treated with salvianolate compared with rats treated with saline. Our findings suggest that salvianolate provides neuroprotective effects against cerebral ischemia-reperfusion injury by upregulating heat shock protein 22 and phosphorylated protein kinase B expression.

  11. Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion

    OpenAIRE

    2013-01-01

    OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, an...

  12. The stability of the atherosclerotic plaque depends on the extent of injured endothelium: results from a novel model of ischemia /reperfusion induced atherosclerosis in carotid artery of rats

    Institute of Scientific and Technical Information of China (English)

    晋学庆

    2014-01-01

    Objective To observe the atherogenic lesion progress in a novel ischemia/reperfusion induced atherosclerosis model in the carotid artery of rats.Methods Rats were divided into normal control,sham-operated control and ischemia-reperfusion injury(IRI)groups(n=10each).IRI was induced by 30 min carotid artery occlusion with a 2 cm

  13. Classical and remote post-conditioning effects on ischemia/reperfusion-induced acute oxidant kidney injury.

    Science.gov (United States)

    Kadkhodaee, Mehri; Najafi, Atefeh; Seifi, Behjat

    2014-11-01

    The present study aimed to analyze and compare the effects of classical and remote ischemic postconditioning (POC) on rat renal ischemia/reperfusion (IR)-induced acute kidney injury. After right nephrectomy, male rats were randomly assigned into four groups (n = 8). In the IR group, 45 min of left renal artery occlusion was induced followed by 24 h of reperfusion. In the classical POC group, after induction of 45 min ischemia, 4 cycles of 10 s of intermittent ischemia and reperfusion were applied to the kidney before complete restoring of renal blood. In the remote POC group, 4 cycles of 5 min ischemia and reperfusion of left femoral artery were applied after 45 min renal ischemia and right at the time of renal reperfusion. There was a reduction in renal function (increase in blood urea and creatinine) in the IR group. Application of both forms of POC prevented the IR-induced reduction in renal function and histology. There were also significant improvements in kidney oxidative stress status in both POC groups demonstrated by a reduction in malondialdehyde (MDA) formation and preservation of antioxidant levels comparing to the IR group. We concluded that both methods of POC have protective effects on renal function and histology possibly by a reduction in IR-induced oxidative stress.

  14. Protective effects of hyperbaric oxygen and iloprost on ischemia/reperfusion-induced lung injury in a rabbit model

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    Bozok Ş

    2012-06-01

    Full Text Available Abstract Background The role of multiorgan damage in the mortality caused by ischemic limb injury is still not clarified. The objective of this study was to examine the potential protective effects of hyperbaric oxygen (HBO and iloprost (IL therapy on lung damage induced by limb ischemia/reperfusion injury in a rabbit model, using both biochemical and histopathological aspects. Methods Forty New Zealand white rabbits were randomly allocated into one of five study groups: HBO group (single session of HBO treatment; IL group (25 ng/kg/min infusion of IL; HBO + IL group (both HBO and IL; Control group (0.9% saline only; and a sham group. Acute hind limb ischemia-reperfusion was established by clamping the abdominal aorta for 1 h. HBO treatment and IL infusion were administrated during 60 min of ischemia and 60 min of reperfusion period. Blood pH, partial pressure of oxygen, partial pressure of carbon dioxide and levels of bicarbonate, sodium, potassium, creatine kinase, lactate dehydrogenase, and tumor necrosis factor alpha were determined at the end of the reperfusion period. Malondialdehyde was measured in the plasma and lung as an indicator of free radicals. After sacrifice, left lungs were removed and histopathological examination determined the degree of lung injury. Results In the control group, blood partial pressure of oxygen and bicarbonate levels were significantly lower and creatine kinase, lactate dehydrogenase, malondialdehyde and tumor necrosis factor-α levels were significantly higher than those of the HBO group, IL group, HBO + IL group and sham group. Similarly, the malondialdehyde levels in the lung tissue and plasma levels were significantly lower in the treatment groups compared with the control group. The extent of lung injury according to the histological findings was significantly higher in the control group. Conclusions These results suggest that both HBO and IL therapies and their combination might be

  15. Effects of exogenous recombinant APC in mouse models of ischemia reperfusion injury and of atherosclerosis.

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    Karin C A A Wildhagen

    Full Text Available Activated protein C (APC is a serine protease that has both anticoagulant and cytoprotective properties. The cytoprotective effects are protease activated receptor 1 (PAR-1 and endothelial protein C receptor (EPCR dependent and likely underlie protective effects of APC in animal models of sepsis, myocardial infarction and ischemic stroke. S360A-(APC, a variant (APC that has no catalytic activity, binds EPCR and shifts pro-inflammatory signaling of the thrombin-PAR-1 complex to anti-inflammatory signaling. In this study we investigated effects of human (hwt-PC, hS360A-PC, hwt-APC and hS360A-APC in acute (mouse model of acute myocardial ischemia/reperfusion (I/R injury and chronic inflammation (apoE-/- mouse model of atherosclerosis. All h(APC variants significantly reduced myocardial infarct area (p<0.05 following I/R injury. IL-6 levels in heart homogenates did not differ significantly between sham, placebo and treatment groups in I/R injury. None of the h(APC variants decreased number and size of atherosclerotic plaques in apoE-/- mice. Only hS360A-APC slightly affected phenotype of plaques. IL-6 levels in plasma were significantly (p<0.001 decreased in hwt-APC and hS360A-PC treated mice. In the last group levels of monocyte chemotactic protein 1 (MCP-1 were significantly increased (p<0.05. In this study we show that both hwt and hS360A-(APC protect against acute myocardial I/R injury, which implies that protection from I/R injury is independent of the proteolytic activity of APC. However, in the chronic atherosclerosis model hwt and hS360-(APC had only minor effects. When the dose, species and mode of (APC administration will be adjusted, we believe that (APC will have potential to influence development of chronic inflammation as occurring during atherosclerosis as well.

  16. High temporal resolution parametric MRI monitoring of the initial ischemia/reperfusion phase in experimental acute kidney injury.

    Science.gov (United States)

    Pohlmann, Andreas; Hentschel, Jan; Fechner, Mandy; Hoff, Uwe; Bubalo, Gordana; Arakelyan, Karen; Cantow, Kathleen; Seeliger, Erdmann; Flemming, Bert; Waiczies, Helmar; Waiczies, Sonia; Schunck, Wolf-Hagen; Dragun, Duska; Niendorf, Thoralf

    2013-01-01

    Ischemia/reperfusion (I/R) injury, a consequence of kidney hypoperfusion or temporary interruption of blood flow is a common cause of acute kidney injury (AKI). There is an unmet need to better understand the mechanisms operative during the initial phase of ischemic AKI. Non-invasive in vivo parametric magnetic resonance imaging (MRI) may elucidate spatio-temporal pathophysiological changes in the kidney by monitoring the MR relaxation parameters T2* and T2, which are known to be sensitive to blood oxygenation. The aim of our study was to establish the technical feasibility of fast continuous T2*/T2 mapping throughout renal I/R. MRI was combined with a remotely controlled I/R model and a segmentation model based semi-automated quantitative analysis. This technique enabled the detailed assessment of in vivo changes in all kidney regions during ischemia and early reperfusion. Significant changes in T2* and T2 were observed shortly after induction of renal ischemia and during the initial reperfusion phase. Our study demonstrated for the first time that continuous and high temporal resolution parametric MRI is feasible for in-vivo monitoring and characterization of I/R induced AKI in rats. This technique may help in the identification of the timeline of key events responsible for development of renal damage in hypoperfusion-induced AKI.

  17. High temporal resolution parametric MRI monitoring of the initial ischemia/reperfusion phase in experimental acute kidney injury.

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    Andreas Pohlmann

    Full Text Available Ischemia/reperfusion (I/R injury, a consequence of kidney hypoperfusion or temporary interruption of blood flow is a common cause of acute kidney injury (AKI. There is an unmet need to better understand the mechanisms operative during the initial phase of ischemic AKI. Non-invasive in vivo parametric magnetic resonance imaging (MRI may elucidate spatio-temporal pathophysiological changes in the kidney by monitoring the MR relaxation parameters T2* and T2, which are known to be sensitive to blood oxygenation. The aim of our study was to establish the technical feasibility of fast continuous T2*/T2 mapping throughout renal I/R. MRI was combined with a remotely controlled I/R model and a segmentation model based semi-automated quantitative analysis. This technique enabled the detailed assessment of in vivo changes in all kidney regions during ischemia and early reperfusion. Significant changes in T2* and T2 were observed shortly after induction of renal ischemia and during the initial reperfusion phase. Our study demonstrated for the first time that continuous and high temporal resolution parametric MRI is feasible for in-vivo monitoring and characterization of I/R induced AKI in rats. This technique may help in the identification of the timeline of key events responsible for development of renal damage in hypoperfusion-induced AKI.

  18. The Influence of Copper (Cu) Deficiency in a Cardiomyocyte Cell Model (HL-1 Cell) of Ischemia/Reperfusion Injury

    Science.gov (United States)

    Mitochondria are important mediators of cell death and this study examines whether mitochondrial dysfunction caused by Cu deprivation promotes cell death in a cell culture model for ischemia/reperfusion injury in cardiomyocytes. HL-1 cells (kindly donated by Dr. William C. Claycomb, LSU Health Scien...

  19. Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.

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    Lan Chen

    Full Text Available OBJECTIVES: Transient receptor potential vanilloid 1 (TRPV1 -positive sensory nerves are widely distributed in the kidney, suggesting that TRPV1-mediated action may participate in the regulation of renal function under pathophysiological conditions. Stimulation of TRPV1 channels protects against ischemia/reperfusion (I/R-induced acute kidney injury (AKI. However, it is unknown whether inhibition of these channels is detrimental in AKI or not. We tested the role of TRPV1 channels in I/R-induced AKI by modulating these channels with capsaicin (TRPV1 agonist, capsazepine (TRPV1 antagonist and using Trpv1-/- mice. METHODS AND RESULTS: Anesthetized C57BL/6 mice were subjected to 25 min of renal ischemia and 24 hrs of reperfusion. Mice were pretreated with capsaicin (0.3 mg/kg body weight or capsazepine (50 mg/kg body weight. Capsaicin ameliorated the outcome of AKI, as measured by serum creatinine levels, tubular damage,neutrophil gelatinase-associated lipocalin (NGAL abundance and Ly-6B.2 positive polymorphonuclear inflammatory cells in injured kidneys. Neither capsazepine nor deficiency of TRPV1 did deteriorate renal function or histology after AKI. Measurements of endovanilloids in kidney tissue indicate that 20-hydroxyeicosatetraeonic acid (20-HETE or epoxyeicosatrienoic acids (EETs are unlikely involved in the beneficial effects of capsaicin on I/R-induced AKI. CONCLUSIONS: Activation of TRPV1 channels ameliorates I/R-induced AKI, but inhibition of these channels does not affect the outcome of AKI. Our results may have clinical implications for long-term safety of renal denervation to treat resistant hypertension in man, with respect to the function of primary sensory nerves in the response of the kidney to ischemic stimuli.

  20. Protective effects of pretreatment with Radix Paeoniae Rubra on acute lung injury induced by intestinal ischemia/ reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    CHEN Chang; ZHANG Fan; XIA Zhong-yuan; LIN Hui; MO An-sheng

    2008-01-01

    Objective: To investigate the effect of pretreatment with Radix Paeoniae Rubra (RPR) on acute lung injury induced by intestinal ischemia/reperfusion in rats and its protective mechanism.Methods:n lung tissues was detected by immunohistochemistry and morphometry computer image analysis. Arterial blood gas analysis, lung permeability index, malondialdehyde (MDA) and superoxide dismutase (SOD) contents in lungs were measured. The histological changes of lung tissue were observed under light microscope.Results:The expression of HO-1 in RPR-pretreatment group and hemin group was obviously higher than that in sham-operation group and I/R group (P < 0.01). The level of MDA and lung permeability index in RPR-pretreatment and hemin group were significantly lower than those in I/R group (P<0.01 or P<0.05), while the activity of SOD in RPR-pretreatment and hemin group was obviously higher than that in I/R group (P<0.01 ). Under light microscope, the pathologic changes induced by I/R were significantly attenuated by RPR.Conclusion : Intestinal ischemia/reperfusion may result in acute lung injury and pretreatment with RPR injection can attenuate the injury. The protective effect of RPR on the acute lung injury is related to its property of inducing HO-1 expression and inhibiting lipid peroxidation.

  1. Changes in corticocerebral morphology in a rat model of focal cerebral ischemia/reperfusion injury following"Xingnao Kaiqiao" acupuncture

    Institute of Scientific and Technical Information of China (English)

    Shu Wang; Zhankui Wang; Guangxia Ni

    2008-01-01

    BACKGROUND: Cerebral ischemia/reperfusion injury has been shown to induce inflammatory reactions,including white blood cell activation and adhesion molecule expression. These reactions often lead to aggravated neuronal injury.OBJECTIVE: To observe corticocerebral pathology, as well as ultrastructural changes, in a rat model of focal cerebral ischemia/reperfusion injury through optical and electron microscopy, and to investigate interventional effects of "Xingnao Kaiqiao" acupuncture (a brain-activating and orifice-opening acupuncture method).DESIGN, TIME AND SETTING: A randomized, controlled, neuropathology, animal experiment was performed at the Laboratory of Molecular Biology, First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine between April and June 2004.MATERIALS: A total of 50 healthy, male, Wistar rats were randomized into 5 groups, with 10 rats per group: control, sham-operated, model, non-acupoint, and "Xingnao Kaiqiao". Transmission electron microscope (TEM 400ST) was provided by Philips, Netherlands. Electro-acupuncture treatment apparatus (KWD-8082) was provided by Changzhou Wujin Great Wall Medical Instrument, China.METHODS: Focal cerebral ischemia/reperfusion injury was induced by occlusion of the middle cerebral artery in the model, non-acupoint, and "Xingnao Kaiqiao" groups. Rats from the control group did not undergo any treatment. The sham-operated group received identical experimental procedures as the model group, except that the nylon suture was not inserted into the right internal carotid artery. At 1, 3, 6, and 12 hours following focal cerebral ischemia/dreperfusion injury induction, rats from the Xingnao Kaiqiao group underwent l-minute acupuncture at the bilateral "Neiguan" (PC 6) acupoint, using a reducing method of lifting-thrusting and twirling-rotating. Subsequently, the rats were subjected to acupuncture at the "Renzhong" (DU26) acupoint 10 times by a heavy bird-pecking method. The non-acupoint group received

  2. Diffusion weighted imaging assessment of acute hepatic ischemia reperfusion injury in rabbit models%弥散加权成像诊断兔急性肝缺血再灌注损伤

    Institute of Scientific and Technical Information of China (English)

    郭成伟; 易贤林; 罗维; 曾琼新; 曹希明; 梁长虹

    2011-01-01

    目的 探讨3.0T MR DWI对兔急性肝脏缺血再灌注损伤(IRI)的诊断价值.方法 新西兰大白兔24只,将其中18只兔制成IRI模型,结扎肝左叶血供60 min后恢复血供,随机分为0.5 h、2 h和6 h组,每组6只;另外6只作为对照组,仅解剖肝十二指肠韧带,未阻断血供.b值分别选取100、200、300、500、600 s/mm2,行T2W、T1W、增强T1W检查,并进行组织病理学检查.结果 IRI后0.5 h,T2WI和DWI表现为整个肝左叶信号增高,在2 h和6 h时出现点片状高信号以及相对应的强化减低区.b=100、200、300 s/mm2时,0.5 h组ADC值明显低于对照组(P<0.05);2 h组ADC值虽有升高(b≤300 s/mm2较明显),但与对照组间差异无统计学意义(P>0.05);b=100 s/mm2时,6 h组与对照组间差异有统计学意义(P<0.05).镜下表现;IRI早期肝细胞弥漫性肿胀、肝窦内、中央静脉及小动脉内大量红细胞淤积.随着损伤加重,肝窦及肝实质内中性粒细胞浸润,肝细胞核固缩凋亡,肝窦解离.结论 应用较小b值(b≤300 mm2/s),3.0T DWI能反映兔肝脏IRI早期阶段的肝血窦淤血等微循环障碍的病理生理过程,对于早期动态监测、预防肝脏IRI具有重要临床意义.%Objective To explore the value of DWI in assessment of acute hepatic ischemia reperfusion injury (IRI) in rabbit models. Methods IRI models were established in 18 New Zealand white rabbits. The rabbit models were then divided into three groups (including 0. 5 h, 2 h and 6 h group, each n=6), undergoing 60 min's left lobar ischemia and following 0. 5, 2 and 6 h reperfusion. The rest 6 rabbits were taken as control group without liver ischemia-inducing. DWI using b values of 100,200,300,500 and 600 s/mm2 was performed with a 3.0T clinical MR scanner in all rabbits to obtain T2WI,T1WI and contrast-enhanced T1WI, respectively. Liver histopathology at different time points were also examined. Results On T2WI and DWI, the signal of the left lobar in 0.5 group increased

  3. Fasciotomy Reduces Compartment Pressures and Improves Recovery in a Porcine Model of Extremity Vascular Injury and Ischemia/Reperfusion

    Science.gov (United States)

    2012-10-01

    Forty female yorkshire (75 ± 5kg) swine (Sus Scrofa ; Midwest Research Swine, 31009 645 th Ave., Gibbon, MN 55335) were housed 7 days prior to the...Burkhardt GE, Spencer JR, Gifford SM, Propper B, Jones L, Sumner N, et al. A large animal survival model (Sus scrofa ) of extremity ischemia/reperfusion and...Williams K, Jones L, et al. The impact of ischemic intervals on neuromuscular recovery in a porcine (Sus scrofa ) survival model of extremity vascular

  4. Sex differences in ischemia/reperfusion-induced acute kidney injury are dependent on the renal sympathetic nervous system.

    Science.gov (United States)

    Tanaka, Ryosuke; Tsutsui, Hidenobu; Ohkita, Mamoru; Takaoka, Masanori; Yukimura, Tokihito; Matsumura, Yasuo

    2013-08-15

    Resistance to ischemic acute kidney injury has been shown to be higher in female rats than in male rats. We found that renal venous norepinephrine overflow after reperfusion played important roles in the development of ischemic acute kidney injury. In the present study, we investigated whether sex differences in the pathogenesis of ischemic acute kidney injury were derived from the renal sympathetic nervous system using male and female Sprague-Dawley rats. Ischemia/reperfusion-induced acute kidney injury was achieved by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. Renal function was impaired after reperfusion in both male and female rats; however, renal dysfunction and histological damage were more severe in male rats than in female rats. Renal venous plasma norepinephrine levels after reperfusion were markedly elevated in male rats, but were not in female rats. These sex differences were eliminated by ovariectomy or treatment with tamoxifen, an estrogen receptor antagonist, in female rats. Furthermore, an intravenous injection of hexamethonium (25mg/kg), a ganglionic blocker, 5 min before ischemia suppressed the elevation in renal venous plasma norepinephrine levels after reperfusion, and attenuated renal dysfunction and histological damage in male rats, and ovariectomized and tamoxifen-treated female rats, but not in intact females. Thus, the present findings confirmed sex differences in the pathogenesis of ischemic acute kidney injury, and showed that the attenuation of ischemia/reperfusion-induced acute kidney injury observed in intact female rats may be dependent on depressing the renal sympathetic nervous system with endogenous estrogen.

  5. Expression of aquaporin-1 and aquaporin-3 in lung tissue of rat model with ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    ZHAO Song; LI Xiang-nan

    2010-01-01

    @@ End-stage lung diseases are common and frequentlyoccurring diseases which are difficult for clinical treatment. In recent years, lung transplantation has become a widely accepted and effective therapeutic option for patients with the end-stage pulmonary diseases. Early pulmonary edema resulting from ischemia-reperfusion injury accounts for the major part of mortality and morbidity after lung transplantation. The water channel proteins in lung injury have been little studied, and their impact on the formation of pulmonary edema remains unclear. In this study, we established a rat lung ischemia-reperfusion model to study its impact on the expressions of water channel proteins in lung tissue and explore a new approach to lung transplantation in pulmonary edema pathogenesis.

  6. The role of polymorphonudear cells in lung ischemia-reperfusion injury in a canine model of pulmonary thromboembolism

    Institute of Scientific and Technical Information of China (English)

    邓朝胜

    2006-01-01

    Objective To explore the effects of polymoronuclear cells (PMN) on lung ischemia-reperfusion(I/R) injury in a canine model of pulmonary thromboembolism. Methods Fifteen dogs were divided into three groups; a sham group (n=5), an ischemia group (n=5) and a reperfusion group (n=5). PMN in the whole blood were isolated with density gradient centrifugation. Apoptosis rate of the PMN was measured through flow cytome-

  7. Antioxidant and antiapoptotic effects of erdosteine in a rat model of ovarian ischemia-reperfusion injury

    Directory of Open Access Journals (Sweden)

    Vedat Ugurel

    2017-01-01

    Full Text Available Objective(s: To evaluate the protective effect of erdosteine, an antiapoptotic and antioxidant agent, on torsion–detorsion evoked histopathological changes in experimental ovarian ischemia-reperfusion (IR injury. Materials and Methods: Eighteen female Wistar albino rats were used in control, IR, and IR+Edosteine (IR-E groups, (n=6 in each. The IR-E group received the erdosteine for seven days before the induction of torsion/retorsion, (10 mg/kg/days. The IR and IR-E groups were exposed to right unilateral adnexal torsion for 3 hr. Three hours later, re-laparotomy was performed, and the right ovaries were surgically excised. Oxidant and antioxidants levels were determined in serum. The ovarian tissue samples were received and fixed with 10% neutral buffered formalin. The sections were stained with H&E, anti-PCNA, and TUNEL. Results: The IR group were showed severe acute inflammation, polynuclear leukocytes and macrophages, stromal oedema and haemorrhage. Treatment with erdosteine in rats significantly retained degenerative changes in the ovaryPCNA (+ cell numbers were significantly decreased in the IR and IR-E groups unlike the control group. However, its numbers were significantly increased in the IR-E group unlike the IR group. TUNEL (+ cell numbers were significantly increased in the IR group unlike the control and the IR-E groups. In erdosteine treated group, TUNEL (+ cells were detected significantly less than the IR group (P

  8. PARP Inhibition Attenuates Histopathological Lesion in Ischemia/Reperfusion Renal Mouse Model after Cold Prolonged Ischemia

    Directory of Open Access Journals (Sweden)

    Raimundo M. G. del Moral

    2013-01-01

    Full Text Available We test the hypothesis that PARP inhibition can decrease acute tubular necrosis (ATN and other renal lesions related to prolonged cold ischemia/reperfusion (IR in kidneys preserved at 4°C in University of Wisconsin (UW solution. Material and Methods. We used 30 male Parp1+/+ wild-type and 15 male Parp10/0 knockout C57BL/6 mice. Fifteen of these wild-type mice were pretreated with 3,4-dihydro-5-[4-(1-piperidinylbutoxyl]-1(2H-isoquinolinone (DPQ at a concentration of 15 mg/kg body weight, used as PARP inhibitor. Subgroups of mice were established (A: IR 45 min/6 h; B: IR + 48 h in UW solution; and C: IR + 48 h in UW solution plus DPQ. We processed samples for morphological, immunohistochemical, ultrastructural, and western-blotting studies. Results. Prolonged cold ischemia time in UW solution increased PARP-1 expression and kidney injury. Preconditioning with PARP inhibitor DPQ plus DPQ supplementation in UW solution decreased PARP-1 nuclear expression in renal tubules and renal damage. Parp10/0 knockout mice were more resistant to IR-induced renal lesion. In conclusion, PARP inhibition attenuates ATN and other IR-related renal lesions in mouse kidneys under prolonged cold storage in UW solution. If confirmed, these data suggest that pharmacological manipulation of PARP activity may have salutary effects in cold-stored organs at transplantation.

  9. Edaravone inhibits apoptosis caused by ischemia/reperfusion injury in a porcine hepatectomy model

    Institute of Scientific and Technical Information of China (English)

    Mitsugi Shimoda; Yoshimi Iwasaki; Toshie Okada; Keiichi Kubota

    2012-01-01

    AIM:To investigate the effect of E3-methyl-1-phenyl-2-pyrazolin-5-one (Edr) on hepatic ischemia-reperfusion (I/R) injury and liver regeneration in a porcine hepatectomy model.METHODS:One hour ischemia was induced by occluding the vessels and the bile duct of the right and median lobes.A 40% left hepatectomy was performed after reperfusion.Six animals received Edr (3 mg/kg per hour)intravenously and six control animals received saline just before reperfusion.Remnant liver volume,hemodynamics,aspartate aminotransferase (AST),alanine aminotransferase,lactate dehydrogenase and lactic acid,were compared between the groups.The expression of transforming growth factor-β (TGF-β1) and toll-like receptor (TRL) mRNA in hepatic tissues was examined using reverse transcription polymerase chain reaction.Apoptosis was demonstrated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining,respectively.RESULTS:Serum AST (P =0.029),and toll like receptor 4 level (P =0.043) were significantly lower after 3 hin animals receiving Edr.In addition,TUNEL staining in Edr-treated pigs showed significantly fewer hepatocytes undergoing apoptosis compared with control pigs.After mo,all factors were non-significantly different between the two groups.CONCLUSION:Edr is considered to reduce hepatic injury in the early stage of I/R injury in a porcine model.

  10. Myocardial contrast echocardiography to assess perfusion in a mouse model of ischemia/reperfusion injury

    Science.gov (United States)

    Hossack, John A.; Li, Yinbo; Christensen, Jonathan P.; Yang, Zequan; French, Brent A.

    2004-04-01

    Noninvasive approaches for measuring anatomical and physiological changes resulting from myocardial ischemia / reperfusion injury in the mouse heart have significant value since the mouse provides a practical, low-cost model for modeling human heart disease. In this work, perfusion was assessed before, during and after an induced closed- chest, coronary ischemic event. Ultrasound contrast agent, similar to MP1950, in a saline suspension, was injected via cannulated carotid artery as a bolus and imaged using a Siemens Sequoia 512 scanner and a 15L8 intraoperative transducer operating in second harmonic imaging mode. Image sequences were transferred from the scanner to a PC for analysis. Regions of interest were defined in septal and anterior segments of the myocardium. During the ischemic event, when perfusion was diminished in the anterior segment, mean video intensity in the affected segment was reduced by one half. Furthermore, following reperfusion, hyperemia (enhanced blood flow) was observed in the anterior segment. Specifically, the mean video intensity in the affected segment was increased by approximately 50% over the original baseline level prior to ischemia. Following the approach of Kaul et al., [1], gamma variate curves were fitted to the time varying level of mean video intensity. This foundation suggests the possibility of quantifying myocardial blood flow in ischemic regions of a mouse heart using automated analysis of contrast image data sets. An improved approach to perfusion assessment using the destruction-reperfusion approach [2] is also presented.

  11. Sildenafil citrate protects skeletal muscle of ischemia-reperfusion injury: immunohistochemical study in rat model

    Directory of Open Access Journals (Sweden)

    Dinani Matoso Fialho de Oliveira Armstrong

    2013-04-01

    Full Text Available PURPOSE: To investigate the effect of sildenafil citrate (SC on skeletal muscle ischemia-reperfusion (IR injury in rats. METHODS: Adult male Wistar rats were randomized into three groups: vehicle-treated control (CTG, sildenafil citrate-treated (SCG, and sham group (SG. CTG and SCG had femoral artery occluded for 6 hours. Saline or 1 mg/kg of SC was given 5.5 hours after occlusion. SG had a similar procedure without artery occlusion. Soleus muscle samples were acquired 4 or 24h after the reperfusion. Immunohistochemistry caspase-3 analysis was used to estimate apoptosis using the apoptotic ratio (computed as positive/negative cells. Wilcoxon rank-sum or Kruskal-Wallis tests were used to assess differences among groups. RESULTS: Eighteen animals were included in the 4h reperfusion groups and 21 animals in the 24h reperfusion groups. The mean apoptotic ratio was 0.18±0.1 for the total cohort; 0.14±0.06 for the 4h reperfusion groups and 0.19±0.08 for the 24h groups (p<0.05. The SCG had lower caspase-3 ratio compared to the control groups at the 24h reperfusion time point (p<0.05. CONCLUSION: Sildenafil citrate administration after the onset of the ischemic injury reduces IR-induced cellular damage in skeletal muscle in this rat hindlimb ischemia model.

  12. Erdosteine improves oxidative damage in a rat model of renal ischemia-reperfusion injury.

    Science.gov (United States)

    Gurel, A; Armutcu, F; Cihan, A; Numanoglu, K V; Unalacak, M

    2004-01-01

    The aim of the present study was to determine the effects of erdosteine, a new antioxidant and anti-inflammatory agent, on lipid peroxidation, neutrophil infiltration, and antioxidant enzyme activities in a rat model of renal ischemia-reperfusion (I/R) injury. Twenty-eight rats were divided into three groups: sham operation, I/R, and I/R plus erdosteine groups. After the experimental procedure, rats were sacrificed and kidneys were removed and prepared for malondialdehyde (MDA) levels, myeloperoxidase (MPO), xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) activities. MDA level, MPO and XO activities were significantly increased in the I/R group. On the other hand, SOD and CAT activities were found to be decreased in the I/R group compared to the sham group. Pretreatment with erdosteine significantly diminished tissue MDA level, MPO and XO activities. Our data support a role for erdosteine in attenuation in renal damage after I/R injury of the kidney, in part at least by inhibition of neutrophil sequestration and XO activity.

  13. Protective role of adiponectin in a rat model of intestinal ischemia reperfusion injury

    Science.gov (United States)

    Liu, Xu-Hui; Yang, Yue-Wu; Dai, Hai-Tao; Cai, Song-Wang; Chen, Rui-Han; Ye, Zhi-Qiang

    2015-01-01

    AIM: To determine the potential protective role of adiponectin in intestinal ischemia reperfusion (I/R) injury. METHODS: A rat model of intestinal I/R injury was established. The serum level of adiponectin in rats with intestinal I/R injury was determined by enzyme-linked immunosorbent assay (ELISA). The serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also measured by ELISA. Apoptosis of intestinal cells was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The production of malondialdehyde (MDA) and superoxide dismutase (SOD) and villous injury scores were also measured. RESULTS: Adiponectin was downregulated in the serum of rats with intestinal I/R injury compared with sham rats. No significant changes in the expression of adiponectin receptor 1 and adiponectin receptor 2 were found between sham and I/R rats. Pre-treatment with recombinant adiponectin attenuated intestinal I/R injury. The production of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, in rats with intestinal I/R injury was reduced by adiponectin pre-treatment. The production of MDA was inhibited, and the release of SOD was restored by adiponectin pre-treatment in rats with intestinal I/R injury. Adiponectin pre-treatment also inhibited cell apoptosis in these rats. Treatment with the AMP-activated protein kinase (AMPK) signaling pathway inhibitor, compound C, or the heme oxygenase 1 (HO-1) inhibitor, Snpp, attenuated the protective effects of adiponectin against intestinal I/R injury. CONCLUSION: Adiponectin exhibits protective effects against intestinal I/R injury, which may involve the AMPK/HO-1 pathway. PMID:26715807

  14. The role and modulation of autophagy in experimental models of myocardial ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Carol Chen-Scarabelli; Richard Knight; Pratik R Agrawal; Louis Saravolatz; Cadigia Abuniat; Gabriele Scarabelli; Anastasis Stephanou; Leena Loomba; Jagat Narula; Tiziano M Scarabelli

    2014-01-01

    A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cyto-plasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion (I/R) injury. This tightly orchestrated cata-bolic cellular‘housekeeping’ process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protec-tive mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the va-riability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin (mTOR) inhibitors, adenosine monophosphate-activated protein kinase (AMPK) modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic ma-nipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling.

  15. Change in kidney morphology after ischemia/reperfusion in a sheep model of acute heart failure supported by pulsatile catheter pump%急性心力衰竭绵羊搏动性导管泵辅助肾缺血-再灌注后的形态学改变

    Institute of Scientific and Technical Information of China (English)

    李智成; 陈长志; 叶清; 成少飞; 王维俊; 汤敏; 赵晓刚; Y.John Gu

    2009-01-01

    BACKGROUND: Acute renal failure following heart failure assisted circulation have been extensively reported. However, little data have been available concerning morphological analysis of kidney tissues under that condition.OBJECTIVE: To observe morphological change of ischemia/reperfusion kidney in a sheep pulsatile catheter (PUCA) pump short-term support for heart failure model and explore causes of acute renal failure in assisted circulation patients.DESIGN, TIME AND SETTING: Self-contrast animal experiment was performed at the laboratory of Department of Cardiothoracic Surgery, Renji Hospital of Shanghai Second Medical University between July 2003 and April 2004.MATERIALS: PUCA pump was provided by Gerhard Rakhorst, Professor of Biomedical Engineering, University of Groningen.METHODS: After ischemic heart failure in 10 sheep was induced successfully and subsequently ischemia/reperfusion kidney was developed, PUCA pump was activated to support the hemodynamics for 3 hours.MAIN OUTCOME MEASURES: Hemodynamic parameters were monitored and recorded before thoracotomy, heart failure, and every 45 minutes after the support. Kidney biopsy specimens for light and electron microscopy were obtained 3 hours after support.RESULTS: PUCA pump support was successful in 7 of 10 sheep for 3 hours. During support with the PUCA pump,Hemodynamic parameters gradually restored to normal and stable condition, and blood pressure was close to baseline at the end of experiment. On both light and electron microscopy examination, mild acute kidney change was observed after ischemia/reperfusion. Cytosis in renal glomerulus associated with vasodilatation hyperemia, endepidermis in renal tubules hydropic degeneration, vasodilatation hyperemia and Interstitial edema in renal medulla were the main findings.CONCLUSION: PUCA pump could successfully maintain the hemodynamics for 3 hours in a sheep acute heart failure model,but pathological change in ischemia/reperfusion kidney was remained. It is

  16. Protective effects of prostaglandin E1 perfusion against spinal cord ischemia-reperfusion injury in a rabbit model

    Institute of Scientific and Technical Information of China (English)

    Xifan Mei; Yansong Wang; Chang Liu

    2008-01-01

    BACKGROUND: Prostaglandin E1 (PGE1) is known to be protective in ischemia-reperfusion of heart, lung, renal, and liver tissue. It still remains to be determined whether PGE1 exhibits similar protection against spinal cord ischemia-reperfusion injury in a rabbit model. OBJECTIVE: To observe the large, ventral horn, motor neurons of the spinal cord, as well as limb function, and to investigate whether perfusion of PGE1 exhibits protective effects against spinal cord ischemia-reperfusion injury in a rabbit model. DESIGN, TIME AND SETTING: Controlled observation. The experiment was performed at the Department of Orthopedics, First Affiliated Hospital of Liaoning Medical University between June and October 2007. MATERIALS: Twenty male, New Zealand white rabbits, weighing 2.0 kg and of mixed gender, were used in the present study. The following chemicals and compounds were used: prostaglandin El injectable powder, as well as malondialdehyde and ATPase kits. Animal intervention was in accordance with animal ethical standards. METHODS: We separated rabbits into control and experimental groups randomly, with 10 rabbits in each group. Rabbits were used as spinal cord ischemia models by segmentally cross-clamping the infrarenal aorta. The control group was subsequently perfused for five minutes with blood and saline solution, and the experimental group was perfused for 5 minutes with blood and saline solution containing PGE1 (100 ng/kg/min). MAIN OUTCOME MEASURES: The neurological function of the hind limbs was assessed 12, 24, and 48 hours after model establishment. All animals were sacrificed and spinal cords were harvested for histological analyses. The large motor neurons in the ventral horn of L1-7 were observed by inverted microscope. RESULTS: All 20 rabbits were included in the final analysis, without any loss. In the ventral horn of the L5-7 segments, there were more large motor neurons that appeared viable in the experimental group than the control group (P<0

  17. Testing Danegaptide Effects on Kidney Function after Ischemia/Reperfusion Injury in a New Porcine Two Week Model

    Science.gov (United States)

    Keller, Anna K.; Hansen, Rie Schultz; Nørregaard, Rikke; Krag, Søren Palmelund; Møldrup, Ulla; Pedersen, Michael; Jespersen, Bente; Birn, Henrik

    2016-01-01

    Introduction Ischemia/reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) and is associated with increased mortality. Danegaptide is a selective modifier of the gap junction protein connexion 43. It has cytoprotective as well as anti-arrhythmic properties and has been shown to reduce the size of myocardial infarct in pigs. The aim of this study was to investigate the ischemia-protective effect of Danegaptide in a porcine renal I/R-I model with two weeks follow up. Methods Unilateral renal I/R-I was induced in pigs by clamping the left renal artery over a two hour period. The model allowed examination of renal blood flow by magnetic resonance imaging (MRI) and the measurement of single kidney GFR two weeks after injury. Eleven animals were randomized to Danegaptide-infusion while nine animals received placebo. Kidney histology and urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion were included as markers of AKI. Results Unilateral kidney I/R-I resulted in an immediate ~50% GFR reduction, associated with a four-fold increase in urinary NGAL-excretion. Fourteen days after I/R-I, the total GFR was ~75% of baseline with a significantly lower GFR in the injured left kidney compared to the right kidney. No differences in GFR were observed between the treated and non-treated animals immediately after I/R-I or at Day 14. Furthermore, no differences were observed in the urinary excretion of NGAL, renal blood flow or other markers of renal function. Conclusions As expected this porcine renal I/R-I model was associated with reduced GFR two weeks after injury. Danegaptide did not improve renal function after I/R-I. PMID:27760220

  18. Effect of infliximab on acute hepatic ischemia/reperfusion injury in rats

    Science.gov (United States)

    Yucel, Ahmet Fikret; Pergel, Ahmet; Aydin, Ibrahim; Alacam, Hasan; Karabicak, Ilhan; Kesicioglu, Tugrul; Tumkaya, Levent; Kalkan, Yildiray; Ozer, Ender; Arslan, Zakir; Sehitoglu, Ibrahim; Sahin, Dursun Ali

    2015-01-01

    This study aimed to investigate the hepatoprotective and antioxidant effects of infliximab (IFX) against liver ischemia/reperfusion (I/R) injury in rats. A total of 30 male Wistar albino rats were divided into three groups: sham, I/R, and I/R+IFX. IFX was given at a dose of 3 mg/kg for three days before I/R. Rat livers were subjected to 60 min of ischemia followed by 90 h of reperfusion. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-α, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured in the serum. The liver was removed to evaluate the histopathologic changes. The I/R group had a significant increase in AST, ALT, MDA, and TNF-α levels, and a decrease in GSH-Px activity compared with the sham group. The use of IFX significantly reduced the ALT, AST, MDA and TNF-α levels and significantly increased GSH-Px activity. IFX attenuated the histopathologic changes. IFX has a protective effect on liver I/R injury. This liver protective effect may be related to antioxidant and anti-TNF-α effects. We propose that, for the relief of liver injury subsequent to transplantation, liver resection, trauma, and shock, tentative treatments can be incorporated with IFX, which is already approved for clinical use. PMID:26885068

  19. Changes of transmural heterogeneity of Cx43 expression in acute myocardial ischemia reperfusion

    Institute of Scientific and Technical Information of China (English)

    Jiang-Hua Zhong; Shi-Juan Lu; Xiao-Pan Chen; Qi Zuo; Zheng-Wang Liu; Ding-Jun Sun; Miao Wu

    2016-01-01

    Objective:To observe the change of transmural heterogeneity of Cx43 protein among three myocardial layers and explore physiological mechanisms of malignant ventricular arrhythmia (MVA) in myocardial ischemia reperfusion (MIR).Methods: Twenty rabbits were randomly divided into MIR group (n=10) which rabbits with MIR were made in and sham group (n=10). 90% monophasic action potential repolarization duration (APD90), transmural dispersion of repolarization (TDR) and Cx43 protein (Cx43-pro) and mRNA (Cx43-Cq) expression among three myocardial layers were measured in both groups.Results:Compared with APD90 and TDR among three myocardial layers in the sham group, those in the MIR group were significant increased (P<0.01), which showed that transmural dispersion of repolarization increased significantly in MIR. Compared to those in the sham group, all three myocardial Cx43-pro significantly decreased (P<0.05) and△Cx43-pro obviously increased (P<0.05) in the MIR group which indicated transmural expression heterogeneity of Cx43 protein enlarged in MIR. 3. Cx43-Cq in all myocardium were significantly reduced (P<0.05) and△Cx43-Cq was significantly increased (P<0.05) in the MIR group compared to those in the sham group, which proved that transmural heterogeneity of Cx43 mRNA raised in MIR.Conclusions:Transmural heterogeneity of Cx43 expression among three myocardial layers in MIR significantly increased, which may enlarge dispersion of repolarization and prone to MVA.

  20. Immediate expression of c-fos and c-jun mRNA in a model of intestinal autotransplantation and ischemia-reperfusion in situ

    Science.gov (United States)

    Santos, Maria Mercês; Tannuri, Ana Cristina Aoun; Coelho, Maria Cecilia Mendonça; de Oliveira Gonçalves, Josiane; Serafini, Suellen; da Silva, Luiz Fernando Ferraz; Tannuri, Uenis

    2015-01-01

    OBJECTIVE: Intestinal ischemia-reperfusion injury occurs in several clinical conditions and after intestinal transplantation. The aim of the present study was to investigate the phenomena of apoptosis and cell proliferation in a previously described intestinal ischemia-reperfusion injury autograft model using immunohistochemical markers. The molecular mechanisms involved in ischemia-reperfusion injury repair were also investigated by measuring the expression of the early activation genes c-fos and c-jun, which induce apoptosis and cell proliferation. MATERIALS AND METHODS: Thirty adult male Wistar rats were subjected to surgery for a previously described ischemia-reperfusion model that preserved the small intestine, the cecum and the ascending colon. Following reperfusion, the cecum was harvested at different time points as a representative segment of the intestine. The rats were allocated to the following four subgroups according to the reperfusion time: subgroup 1: 5 min; subgroup 2: 15 min; subgroup 3: 30 min; and subgroup 4: 60 min. A control group of cecum samples was also collected. The expression of c-fos, c-jun and immunohistochemical markers of cell proliferation and apoptosis (Ki67 and TUNEL, respectively) was studied. RESULTS: The expression of both c-fos and c-jun in the cecum was increased beginning at 5 min after ischemia-reperfusion compared with the control. The expression of c-fos began to increase at 5 min, peaked at 30 min, and exhibited a declining tendency at 60 min after reperfusion. A progressive increase in c-jun expression was observed. Immunohistochemical analyses confirmed these observations. CONCLUSION: The early activation of the c-fos and c-jun genes occurred after intestinal ischemia-reperfusion injury, and these genes can act together to trigger cell proliferation and apoptosis. PMID:26039956

  1. Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

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    Xiaolin He

    Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

  2. Edaravone attenuates ischemia-reperfusion injury by inhibiting oxidative stress in a canine lung transplantation model

    Institute of Scientific and Technical Information of China (English)

    XU Jin-zhi; SHEN Bao-zhong; LI Ye; ZHANG Tong; XU Wan-hai; LIU Xiao-wei; LU Hong-guang

    2008-01-01

    Background Previous reports have confirmed that edaravone has protective effects against ischemia-reperfusion(IR) injury of many organs.In this study,we investigated the effect of edaravone on preventing IR injury of the lung in a canine lung transplantation model. Methods Twelve weight-matched pairs of random-bred dogs were randomized into two groups.Within each pair,one dog served as donor and the other as recipient.In the study group,prostaglandin EI(PGEl)(8 μg/kg)was injected into the donor pulmonary artery(PA)before occlusion and the donor lungs were flushed with 1.0L of LPD solution containing edaravone(10mg/kg)and stored in the same LPD solution at a temperature of 1.C for 8 hours.The left single lung transplantation was then performed and recipients received intravenous injection with edaravone l 1 0 mg/kg)at the onset of reperfusion.In the control group,edaravone was substituted by the same volume of sterile saline solution.Another six dogs were obtained as normal control group in which left lungs were dissected after thoracotomy without an IR injury.One hour after repeffusion.or after dissection of the left lung,the right lung was excluded from peffusion and ventilation after which,cardiopulmonary parameters were measured.Wet/dry ratios,malondiaIdehyde(MDA)and myeloperoxidase (MPO)levels were assessed and histological analysis of lung tissue performed at the same time.Results All animals survived until the end of the experiment.The study group showed significantly decreased wet/dry ratios(treated:(74.1±4.2)%vs control:(86.8±5.2)%,P<0.01),MDA levels(treated:0.50±0.08 vs control:0.88±0.15,P <0.01)and MPO activity(treated:0.23±0.05 vs control:0.43±0.07,P

  3. Age-related differences of neutrophil activation in a skeletal muscle ischemia-reperfusion model.

    Science.gov (United States)

    Mowlavi, Arian; Reynolds, Christopher; Neumeister, Michael W; Wilhelmi, Bradon J; Song, Yao-Hua; Naffziger, Ryan; Glatz, Frank R; Russell, Robert C

    2003-04-01

    Free tissue transfers and replantation of amputated limbs are better tolerated by young adolescents than mature adults. The authors hypothesized that this observation may be, in part, because of an attenuated ischemia-reperfusion (IR) injury in younger patients. Because neutrophils have been identified as a critical cell line responsible for IR injury, the authors investigated the effects of animal age on the degree of neutrophil activation in a rat model. Activation was evaluated by monitoring expression of integrin surface markers (mean fluorescence intensity [MFI] of CD11b) and oxidative burst potential (MFI of dihydrorhodamine [DHR] oxidation) by flow cytometry in neutrophils analyzed after 4 hours of ischemia and 1, 4, and 16 hours of reperfusion in a gracilis muscle flap model in mature adult and young adolescent rats. Neutrophil activation was also evaluated in control sham-operated animals, which underwent elevation of gracilis muscle flaps without exposure to an ischemic insult. Muscle edema, determined by wet-to-dry muscle weight ratio, and muscle viability, determined by nitro blue tetrazolium (NBT) staining, were completed for gracilis muscles exposed to ischemia after 24 hours of reperfusion for each of the groups. Integrin expression, assessed by MFI of CD11b, was increased significantly in ischemic muscles of mature adult rats at 4 hours of reperfusion (71.10+/-3.53 MFI vs. 54.88+/-12.73 MFI, p=0.025). Neutrophil oxidative potential, assessed by MFI of DHR oxidation, was increased significantly in ischemic muscles of mature adult rats compared with young adolescent rats at 1 hour of reperfusion (78.10+/-9.53 MFI vs. 51.78+/-16.91 MFI, p=0.035) and 4 hours of reperfusion (83.69+/-15.29 MFI vs. 46.55+/-8.09 MFI, p=0.005). Increased edema formation was observed in the ischemic muscles of mature adult rats when compared with young adolescent rats (1.25+/-0.04 vs. 1.12+/-0.05, p=0.031) after 24 hours of reperfusion. A trend toward decreased muscle

  4. Hippophae salicifolia D.Don berries attenuate cerebral ischemia reperfusion injury in a rat model of middle cerebral artery occlusion

    Institute of Scientific and Technical Information of China (English)

    Santhrani Thakur; Pradeepthi Chilikuri; Bindu Pulugurtha; Lavanya Yaidikar

    2015-01-01

    Objective: To investigate the protective effect of Hippophae salicifolia D.Don (H. salicifolia) berries extract against cerebral reperfusion injury induced neurobehavioral and neurochemical changes in a rat model of middle cerebral artery occlusion (MCAO). Methods: Rats were pretreated with alcoholic extract of H. salicifolia (250 and 500 mg/kg) for 14 d and focal cerebral ischemia was induced by MCAO. After 60 min of MCAO, reperfused for 24 h, a battery of behavioral tests were assessed the extent of neurological deficits. Infarct volume and brain edema were measured in 2,3,5-triphenyltetrazolium chloride stained brain sections. TNF-α, oxidative stress parameters like reduced glutathione, calcium, glutamate, malondialdehyde and apoptotic parameters like caspase-3, and caspase-9 were estimated in the brain homogenates. Results:Pretreatment with alcoholic extract of H. salicifolia at doses of 250 and 500 mg/kg significantly improved the neurobehavioral alterations and reduced the infarct volume, edema induced by ischemia reperfusion injury. H. salicifolia significantly prevented ischemia induced increase in malondialdehyde, glutamate, calcium, caspase-3, caspase-9 and TNF-αlevels as compared to ischemic animals. Conclusions: Our results indicate that H. salicifolia mitigated the ischemia reperfusion induced neuronal damage.

  5. Ischemic post-conditioning attenuates acute lung injury induced by intestinal ischemia-reperfusion in mice: role of Nrf2.

    Science.gov (United States)

    Meng, Qing-Tao; Cao, Chen; Wu, Yang; Liu, Hui-Min; Li, Wei; Sun, Qian; Chen, Rong; Xiao, Yong-Guang; Tang, Ling-Hua; Jiang, Ying; Leng, Yan; Lei, Shao-Qing; Lee, Chris C; Barry, Devin M; Chen, Xiangdong; Xia, Zhong-Yuan

    2016-10-01

    Intestinal ischemic post-conditioning (IPo) protects against lung injury induced by intestinal ischemia-reperfusion (IIR) partly through promotion of expression and function of heme oxygenase-1 (HO-1). NF-E2-related factor-2 (Nrf2) is a key transcription factor that interacts with HO-1 and regulates antioxidant defense. However, the role of Nrf2 in IPo protection of IIR-induced pulmonary injury is not completely understood. Here we show that IPo significantly attenuated IIR-induced lung injury and suppressed oxidative stress and systemic inflammatory responses. IPo also increased the expression of both Nrf2 and HO-1. Consistently, the beneficial effects of IPo were abolished by ATRA and Brusatol, potent inhibitors of Nrf2. Moreover, the Nrf2 agonist t-BHQ showed similar activity as IPo. Taken together, our data suggest that Nrf2 activity, along with HO-1, plays an important role in the protective effects of IPo against IIR-induced acute lung injury.

  6. Mechanism of Mitochondrial Connexin43′s Protection of the Neurovascular Unit under Acute Cerebral Ischemia-Reperfusion Injury

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    Shuai Hou

    2016-05-01

    Full Text Available We observed mitochondrial connexin43 (mtCx43 expression under cerebral ischemia-reperfusion (I/R injury, analyzed its regulation, and explored its protective mechanisms. Wistar rats were divided into groups based on injections received before middle cerebral artery occlusion (MCAO. Cerebral infarction volume was detected by 2,3,5-triphenyltetrazolim chloride staining, and cell apoptosis was observed by transferase dUTP nick end labeling. We used transmission electron microscopy to observe mitochondrial morphology and determined superoxide dismutase (SOD activity and malondialdehyde (MDA content. MtCx43, p-mtCx43, protein kinase C (PKC, and p-PKC expression were detected by Western blot. Compared with those in the IR group, cerebral infarction volumes in the carbenoxolone (CBX and diazoxide (DZX groups were obviously smaller, and the apoptosis indices were down-regulated. Mitochondrial morphology was damaged after I/R, especially in the IR and 5-hydroxydecanoic acid (5-HD groups. Similarly, decreased SOD activity and increased MDA were observed after MCAO; CBX, DZX, and phorbol-12-myristate-13-acetate (PMA reduced mitochondrial functional injury. Expression of mtCx43 and p-mtCx43 and the p-Cx43/Cx43 ratio were significantly lower in the IR group than in the sham group. These abnormalities were ameliorated by CBX, DZX, and PMA. MtCx43 may protect the neurovascular unit from acute cerebral IR injury via PKC activation induced by mitoKATP channel agonists.

  7. Hydroxyfasudil-mediated inhibition of ROCK1 and ROCK2 improves kidney function in rat renal acute ischemia-reperfusion injury.

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    Dominik Kentrup

    Full Text Available Renal ischemia-reperfusion (IR injury (IRI is a common and important trigger of acute renal injury (AKI. It is inevitably linked to transplantation. Involving both, the innate and the adaptive immune response, IRI causes subsequent sterile inflammation. Attraction to and transmigration of immune cells into the interstitium is associated with increased vascular permeability and loss of endothelial and tubular epithelial cell integrity. Considering the important role of cytoskeletal reorganization, mainly regulated by RhoGTPases, in the development of IRI we hypothesized that a preventive, selective inhibition of the Rho effector Rho-associated coiled coil containing protein kinase (ROCK by hydroxyfasudil may improve renal IRI outcome. Using an IRI-based animal model of AKI in male Sprague Dawley rats, animals treated with hydroxyfasudil showed reduced proteinuria and polyuria as well as increased urine osmolarity when compared with sham-treated animals. In addition, renal perfusion (as assessed by (18F-fluoride Positron Emission Tomography (PET, creatinine- and urea-clearances improved significantly. Moreover, endothelial leakage and renal inflammation was significantly reduced as determined by histology, (18F-fluordesoxyglucose-microautoradiography, Evans Blue, and real-time PCR analysis. We conclude from our study that ROCK-inhibition by hydroxyfasudil significantly improves kidney function in a rat model of acute renal IRI and is therefore a potential new therapeutic option in humans.

  8. miR-1 exacerbates cardiac ischemia-reperfusion injury in mouse models.

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    Zhenwei Pan

    Full Text Available Recent studies have revealed the critical role of microRNAs (miRNAs in regulating cardiac injury. Among them, the cardiac enriched microRNA-1(miR-1 has been extensively investigated and proven to be detrimental to cardiac myocytes. However, solid in vivo evidence for the role of miR-1 in cardiac injury is still missing and the potential therapeutic advantages of systemic knockdown of miR-1 expression remained unexplored. In this study, miR-1 transgenic (miR-1 Tg mice and locked nucleic acid modified oligonucleotide against miR-1 (LNA-antimiR-1 were used to explore the effects of miR-1 on cardiac ischemia/reperfusion injury (30 min ischemia followed by 24 h reperfusion. The cardiac miR-1 level was significantly increased in miR-1 Tg mice, and suppressed in LNA-antimiR-1 treated mice. When subjected to ischemia/reperfusion injury, miR-1 overexpression exacerbated cardiac injury, manifested by increased LDH, CK levels, caspase-3 expression, apoptosis and cardiac infarct area. On the contrary, LNA-antimiR-1 treatment significantly attenuated cardiac ischemia/reperfusion injury. The expression of PKCε and HSP60 was significantly repressed by miR-1 and enhanced by miR-1 knockdown, which may be a molecular mechanism for the role miR-1 in cardiac injury. Moreover, luciferase assay confirmed the direct regulation of miR-1 on protein kinase C epsilon (PKCε and heat shock protein 60 (HSP60. In summary, this study demonstrated that miR-1 is a causal factor for cardiac injury and systemic LNA-antimiR-1 therapy is effective in ameliorating the problem.

  9. Antioxidant and antiapoptotic effects of erdosteine in a rat model of ovarian ischemia-reperfusion injury

    OpenAIRE

    Ugurel, Vedat; Cicek, Ahmet Cagatay; Cemek, Mustafa; Demirtas, Selim; Kocaman, A Tuba; Karaca, Turan

    2017-01-01

    Objective(s): To evaluate the protective effect of erdosteine, an antiapoptotic and antioxidant agent, on torsion–detorsion evoked histopathological changes in experimental ovarian ischemia-reperfusion (IR) injury. Materials and Methods: Eighteen female Wistar albino rats were used in control, IR, and IR+Edosteine (IR-E) groups, (n=6 in each). The IR-E group received the erdosteine for seven days before the induction of torsion/retorsion, (10 mg/kg/days). The IR and IR-E groups were exposed t...

  10. Protective effect of moxonidine on ischemia/reperfusion-induced acute kidney injury through α2/imidazoline I1 receptor.

    Science.gov (United States)

    Tsutsui, Hidenobu; Sugiura, Takahiro; Hayashi, Kentaro; Yukimura, Tokihito; Ohkita, Mamoru; Takaoka, Masanori; Matsumura, Yasuo

    2013-10-15

    Enhancement of renal sympathetic nerve activity during renal ischemia and norepinephrine overflow from the kidney after reperfusion play important roles in the development of ischemic acute kidney injury. Recently, we have found that moxonidine, an α2/imidazoline Ι1-receptor agonist, has preventive effects on ischemic acute kidney injury by suppressing the excitation of renal sympathetic nervous system after reperfusion. In the present study, to clarify the renoprotective mechanisms of moxonidine (360 nmol/kg, i.v.) against ischemic acute kidney injury, we investigated the effect of intravenous (i.v.) and intracerebroventricular (i.c.v.) injection of efaroxan, an α2/Ι1 receptor antagonist, on the moxonidine-exhibited actions. Ischemic acute kidney injury was induced by clamping the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. The suppressive effect of moxonidine on enhanced renal sympathetic nerve activity during renal ischemia was not observed in the rat treated with either i.v. (360 nmol/kg) or i.c.v. (36 nmol/kg) of efaroxan. Furthermore, i.v. injection of efaroxan eliminated the preventive effect of moxonidine on ischemia/reperfusion-induced kidney injury and norepinephrine overflow, and i.c.v. injection of efaroxan did not completely inhibit the moxonidine's effects. These results indicate that moxonidine prevents the ischemic kidney injury by sympathoinhibitory effect probably via α2/Ι1 receptors in central nervous system and by suppressing the norepinephrine overflow through α2/Ι1 receptors on sympathetic nerve endings.

  11. Batroxobin plus hypothermia for protection of cerebral ischemia/reperfusion injury models in gerbils

    Institute of Scientific and Technical Information of China (English)

    Lin Zhang; Pixing Zhang; Yinming Zeng; Qun Chen

    2006-01-01

    BACKGROUND: Hypothermia plays a protective role in cerebral ischemia/reperfusion injury. Dose combination with batroxobin, an active drug for treating cerebrovascular disease, will enhance its protection? OBJECTIVE: To explore the effects of hypothermia, batroxobin, hypothermia combined with batroxobin on complete cerebral ischemia/reperfusion injury in gerbils.DESIGN: A randomized block comparison observation. SETTING: Jiangsu Key Lab of Anesthesiology. MATERIALS: Experimental animal: Sixty Mongolia gerbils weighing 50-80 g, male or female, were provided by the Animals Center of Xuzhou Medical College. Drugs and agents: Batroxobin was provided by Dongling Phar maceutical Industry Organization (Japan). Superoxide dismutase (SOD) and malondiadehyde (MDA) kits were offered by Nanjing Jiancheng Bioengineering Institute. Other reagents were all import or national analytical pure grade. HITACHI R22A refrigerated high-speed centrifuge, and HARRIS ultra-hypothermia refrigerator were used.METHODS: The experiments were completed in Jiangsu Key Lab of Anesthesiology from May 2004 to January 2005. ① The animals were divided into 6 groups by random member table method: sham-operated group (n =6), ischemia control group (n =6), normothermia group (n =12), hypothermia group (n =12), batroxobin group (n =12) and hypothermia+batroxobin group (n =12). Gerbil rats were abdominally anesthetized with sodium pentobarbital. The neck skin was incised to separate bilateral common carotid arteries. Complete cerebral ischemia models were established by occluding bilateral common carotid arteries with artery clamp for 10 minutes, then the clamp was loosened to perfuse the arteries. Iso-electric level of brain electric wave showed the models were established successfully. The gerbils in the batroxobin group and hypothermia+batroxobin group were abdominally injected with batroxobin (8 BU/kg) while reperfusion, and isovolumetric saline was administered to the gerbils in the other groups

  12. The Current State of Knowledge of Hepatic Ischemia-Reperfusion Injury Based on Its Study in Experimental Models

    Science.gov (United States)

    Mendes-Braz, M.; Elias-Miró, M.; Jiménez-Castro, M. B.; Casillas-Ramírez, A.; Ramalho, F. S.; Peralta, C.

    2012-01-01

    The present review focuses on the numerous experimental models used to study the complexity of hepatic ischemia/reperfusion (I/R) injury. Although experimental models of hepatic I/R injury represent a compromise between the clinical reality and experimental simplification, the clinical transfer of experimental results is problematic because of anatomical and physiological differences and the inevitable simplification of experimental work. In this review, the strengths and limitations of the various models of hepatic I/R are discussed. Several strategies to protect the liver from I/R injury have been developed in animal models and, some of these, might find their way into clinical practice. We also attempt to highlight the fact that the mechanisms responsible for hepatic I/R injury depend on the experimental model used, and therefore the therapeutic strategies also differ according to the model used. Thus, the choice of model must therefore be adapted to the clinical question being answered. PMID:22649277

  13. A novel cardioprotective agent in cardiac transplantation: metformin activation of AMP-activated protein kinase decreases acute ischemia-reperfusion injury and chronic rejection.

    Science.gov (United States)

    Chin, Jocelyn T; Troke, Joshua J; Kimura, Naoyuki; Itoh, Satoshi; Wang, Xi; Palmer, Owen P; Robbins, Robert C; Fischbein, Michael P

    2011-12-01

    The main cause of mortality after the first year from cardiac transplantation is cardiac allograft vasculopathy (CAV), which leads to chronic rejection of the heart. To improve long-term outcomes in cardiac transplantation, treatments to prevent or diminish CAV are actively being researched. Ischemia-reperfusion (I-R) injury has been shown to be the strongest alloantigen-independent factor in the development of CAV. Here, we investigate the use of metformin in murine cardiac transplantation models as a novel cardioprotective agent to limit acute I-R injury and subsequent chronic rejection. We show that metformin treatment activates AMP-activated kinase (AMPK) in vitro and in vivo. In the acute transplantation model, metformin activation of AMPK resulted in significantly decreased apoptosis in cardiac allografts on postoperative day (POD) 1 and 8. In the chronic transplantation model, metformin pretreatment of allografts led to significantly improved graft function and significantly decreased CAV, as measured on POD 52. Taken together, our results in the acute and chronic rejection studies suggest a potential cardioprotective mechanism for metformin; we demonstrate a correlation between metformin-induced decrease in acute I-R injury and metformin-related decrease in chronic rejection. Thus, one of the ways by which metformin and AMPK activation may protect the transplanted heart from chronic rejection is by decreasing initial I-R injury inherent in donor organ preservation and implantation. Our findings suggest novel therapeutic strategies for minimizing chronic cardiac rejection via the use of metformin- and AMPK-mediated pathways to suppress acute I-R injury.

  14. Mechanisms of electroacupuncture effects on acute cerebral ischemia/reperfusion injur y:possible association with upregulation of transforming growth factor beta 1

    Institute of Scientific and Technical Information of China (English)

    Wen-biao Wang; Lai-fu Yang; Qing-song He; Tong Li; Yi-yong Ma; Ping Zhang; Yi-sheng Cao

    2016-01-01

    Electroacupuncture at the head acupoints Baihui (GV20) and Shuigou (GV26) improves recovery of neurological function following isch-emic cerebrovascular events, but its mechanism remains incompletely understood. We hypothesized that the action of electroacupuncture at these acupoints is associated with elevated serum levels of transforming growth factor beta 1 (TGF-β1). To test this, we established a rat model of cerebral ischemia by middle cerebral artery occlusion. Electroacupuncture was performed at Baihui and Shuigou with a“disperse-dense”wave at an alternating frequency of 2 and 150 Hz, and at a constant intensity of 3 mA. Each electroacupuncture session lasted 30 minutes and was performed every 12 hours for 3 days. Neurological severity scores were lower in injured rats after acupuncture than in those not subjected to treatment. Furthermore, serum level of TGF-β1 was greater after electroacupuncture than after no treatment. Our results indicate that electroacupuncture at Baihui and Shuigou increases the serum level of TGF-β1 in rats with acute cerebral ischemia/reperfusion injury, and exerts neuroprotective effects.

  15. Effect of U-74500A, a 21-aminosteroid on renal ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Kaur, Hitchintan; Satyanarayana, Padi S V; Chopra, Kanwaljit

    2003-03-01

    Renal ischemia-reperfusion injury constitutes the most common pathogenic factor for acute renal failure and is the main contributor to renal dysfunction in allograft recipients and revascularization surgeries. Many studies have demonstrated that reactive oxygen species play an important role in ischemic acute renal failure. The aim of the present study was to investigate the effects of the synthetic antioxidant U-74500A, a 21-aminosteroid in a rat model of renal ischemia-reperfusion injury. Renal ischemia-reperfusion was induced by clamping unilateral renal artery for 45 min followed by 24 h of reperfusion. Two doses of U-74500A (4.0 mg/kg, i.v.) were administered 45 min prior to renal artery occlusion and then 15 min prior to reperfusion. Tissue lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS) in kidney homogenates. Renal function was assessed by estimating serum creatinine, blood urea nitrogen (BUN), creatinine and urea clearance. Renal morphological alterations were assessed by histopathological examination of hematoxylin-eosin stained sections of the kidneys. Ischemia-reperfusion produced elevated levels of TBARS and deteriorated the renal function as assessed by increased serum creatinine, BUN and decreased creatinine and urea clearance as compared to sham operated rats. The ischemic kidneys of rats showed severe hyaline casts, epithelial swelling, proteinaceous debris, tubular necrosis, medullary congestion and hemorrhage. U-74500A markedly attenuated elevated levels of TBARS as well as morphological changes, but did not improve renal dysfunction in rats subjected to renal ischemia-reperfusion. These results clearly demonstrate the in vivo antioxidant effect of U-74500A, a 21-aminosteroid in attenuating renal ischemia-reperfusion injury.

  16. Endothelial dysfunction of bypass graft: direct comparison of in vitro and in vivo models of ischemia-reperfusion injury.

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    Gábor Veres

    Full Text Available Although, ischemia/reperfusion induced vascular dysfunction has been widely described, no comparative study of in vivo- and in vitro-models exist. In this study, we provide a direct comparison between models (A ischemic storage and in-vitro reoxygenation (B ischemic storage and in vitro reperfusion (C ischemic storage and in-vivo reperfusion.Aortic arches from rats were stored for 2 hours in saline. Arches were then (A in vitro reoxygenated (B in vitro incubated in hypochlorite for 30 minutes (C in vivo reperfused after heterotransplantation (2, 24 hours and 7 days reperfusion. Endothelium-dependent and independent vasorelaxations were assessed in organ bath. DNA strand breaks were assessed by TUNEL-method, mRNA expressions (caspase-3, bax, bcl-2, eNOS by quantitative real-time PCR, proteins by Western blot analysis and the expression of CD-31 by immunochemistry. Endothelium-dependent maximal relaxation was drastically reduced in the in-vivo models compared to ischemic storage and in-vitro reperfusion group, and no difference showed between ischemic storage and control group. CD31-staining showed significantly lower endothelium surface ratio in-vivo, which correlated with TUNEL-positive ratio. Increased mRNA and protein levels of pro- and anti-apoptotic gens indicated a significantly higher damage in the in-vivo models.Even short-period of ischemia induces severe endothelial damage (in-vivo reperfusion model. In-vitro models of ischemia-reperfusion injury can be limitedly suited for reliable investigations. Time course of endothelial stunning is also described.

  17. Long-term existence of cerebral hypoxic tissue in a rat model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Yidong Wang; Jingrui Pan; Yu Qiu; Xiangpen Li; Mei Li; Ying Peng

    2009-01-01

    BACKGROUND: Hypoxic tissue surrounding the ischemic core may represent the ischemic penumbra following cerebral infarction. However, some studies have shown that the duration of ischemic tissue is longer than previously believed.OBJECTIVE: To clarify whether cerebral hypoxic tissue could survive long-term and whether it is altered in rats following cerebral infarction; to establish an ischemia/reperfusion model in which hypoxic tissue exists for extended periods of time.DESIGN, TIME AND SETTING: A completely randomized grouping and controlled experiment was performed at the Experimental Animal Center of Sun Yat-sen University and Medical Research Center, the Second Affiliated Hospital of Sun Yat-sen University between June and December 2008. MATERIALS: 4,9-diaza-3,3,10,10-tetramethyldodecan-2, 11-dione dioxime (BnAO) (HL91), used as the hypoxic marker for autoradiography, was supplied by the Beijing Syncor Star Medicinal, China, and the flesh eluent Na99TcmO4 to mark HL91 was supplied by Guangzhou Medical Isotope Center of the China Institute of Atomic Energy. 2-(2-nitro-1H-imidazole-1-yl)-N-(2,2,3,3,3-pentafluoropropyl) acetamide (EF5) and its antibody ELK3-51, used as a hypoxic marker for immunofluorescence, were supplied by the University of Pennsylvania, USA.METHODS: Male Sprague Dawley rats were randomly divided into four groups: 1.5-hour ischemia/reperfusion group (1.5 h IR), 2-hour ischemia/reperfusion group (2 h IR), 3-hour ischemia/reperfusion group (3 h IR), and permanent ischemia (PI) group, with 21 rats in each group. The middle cerebral artery occlusion model was established using the intraluminal suture method, while reperfusion was performed by removing the suture at each observation time point. However, in the PI group, the suture was left in the artery.MAIN OUTCOME MEASURES: Area and average absorbance of fluorescence, representing hypoxic tissue, were measured by image-analysis.RESULTS: Autoradiography revealed positive hypoxia at days 1 and 14

  18. Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model

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    Arheden Håkan

    2010-09-01

    Full Text Available Abstract Background Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. Methods In anesthetized pigs (42-53 kg, a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8 or saline (9 mg/ml, n = 8. Area at risk (AAR was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. Results ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007. Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23. The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. Conclusions ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability.

  19. Renoprotective effect of paricalcitol via a modulation of the TLR4-NF-κB pathway in ischemia/reperfusion-induced acute kidney injury

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    Lee, Jae-Won, E-mail: maestro97@hanmail.net; Kim, Sun Chul, E-mail: linefe99@hanmail.net; Ko, Yoon Sook, E-mail: rainboweyes@hanmail.net; Lee, Hee Young, E-mail: cell1023@hanmail.net; Cho, Eunjung, E-mail: icdej@naver.com; Kim, Myung-Gyu, E-mail: gyu219@hanmail.net; Jo, Sang-Kyung, E-mail: sang-kyung@korea.ac.kr; Cho, Won Yong, E-mail: wonyong@korea.ac.kr; Kim, Hyoung Kyu, E-mail: hyoung@korea.ac.kr

    2014-02-07

    Highlights: • Paricalcitol. • Attenuation of renal inflammation. • Modulation of TLR4-NF-κB signaling. - Abstract: Background: The pathophysiology of ischemic acute kidney injury (AKI) is thought to include a complex interplay between vascular endothelial cell dysfunction, inflammation, and tubular cell damage. Several lines of evidence suggest a potential anti-inflammatory effect of vitamin D in various kidney injury models. In this study, we investigated the effect of paricalcitol, a synthetic vitamin D analog, on renal inflammation in a mouse model of ischemia/reperfusion (I/R) induced acute kidney injury (AKI). Methods: Paricalcitol was administered via intraperitoneal (IP) injection at 24 h before ischemia, and then I/R was performed through bilateral clamping of the renal pedicles. Twenty-four hours after I/R, mice were sacrificed for the evaluation of injury and inflammation. Additionally, an in vitro experiment using HK-2 cells was also performed to examine the direct effect of paricalcitol on tubular cells. Results: Pre-treatment with paricalcitol attenuated functional deterioration and histological damage in I/R induced AKI, and significantly decreased tissue neutrophil and macrophage infiltration and the levels of chemokines, the pro-inflammatory cytokine interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). It also decreased IR-induced upregulation of Toll-like receptor 4 (TLR4), and nuclear translocation of p65 subunit of NF-κB. Results from the in vitro study showed pre-treatment with paricalcitol suppressed the TNF-α-induced depletion of cytosolic IκB in HK-2 cells. Conclusion: These results demonstrate that pre-treatment with paricalcitol has a renoprotective effect in ischemic AKI, possibly by suppressing TLR4-NF-κB mediated inflammation.

  20. Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury

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    Luca Villa

    2016-10-01

    Full Text Available Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI. We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1 normal; (2 infused for eight weeks with ouabain (30 µg/kg/day, OHR or (3 saline; (4 ouabain; or (5 saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks. In group 1, 2–3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2 increased blood pressure (from 111.7 to 153.4 mmHg and ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI, nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3. All these changes were blunted by rostafuroxin treatment (groups 4 and 5. These findings support the role of EO in IRI and suggest that rostafuroxin pre-treatment of patients before partial nephrectomy with warm ischemia may reduce IRI, particularly in those with high EO.

  1. Ouabain Contributes to Kidney Damage in a Rat Model of Renal Ischemia-Reperfusion Injury

    Science.gov (United States)

    Villa, Luca; Buono, Roberta; Ferrandi, Mara; Molinari, Isabella; Benigni, Fabio; Bettiga, Arianna; Colciago, Giorgia; Ikehata, Masami; Messaggio, Elisabetta; Rastaldi, Maria Pia; Montorsi, Francesco; Salonia, Andrea; Manunta, Paolo

    2016-01-01

    Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO) is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI). We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase) and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1) normal; (2) infused for eight weeks with ouabain (30 µg/kg/day, OHR) or (3) saline; (4) ouabain; or (5) saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks. In group 1, 2–3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2) increased blood pressure (from 111.7 to 153.4 mmHg) and ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI, nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3). All these changes were blunted by rostafuroxin treatment (groups 4 and 5). These findings support the role of EO in IRI and suggest that rostafuroxin pre-treatment of patients before partial nephrectomy with warm ischemia may reduce IRI, particularly in those with high EO. PMID:27754425

  2. Increasing Cycles of Intermittent Ischemia Can Effectively Maintain Liver Function during the Acute Phase of Ischemia Reperfusion Injury by Promotion of Bile Flow and Reduction in Bile Salt Toxicity

    NARCIS (Netherlands)

    Peters, J.; Nieuwenhuijs, V. B.; Morphett, A.; Porte, R. J.; Padbury, R. T. A.; Barritt, G. J.

    2009-01-01

    Background/Aims: Intermittent ischemia (INT) can improve liver function following inflow occlusion. The aim was to test whether the number of cycles of INT can be increased without impairing liver function. Methods: Liver function in the acute phase of ischemia reperfusion injury was assessed by mea

  3. RC-3095, a Selective Gastrin-Releasing Peptide Receptor Antagonist, Does Not Protect the Lungs in an Experimental Model of Lung Ischemia-Reperfusion Injury

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    Vera L. Oliveira-Freitas

    2015-01-01

    Full Text Available RC-3095, a selective GRPR antagonist, has been shown to have anti-inflammatory properties in different models of inflammation. However, its protective effect on lungs submitted to lung ischemia-reperfusion injury has not been addressed before. Then, we administrated RC-3095 intravenously before and after lung reperfusion using an animal model of lung ischemia-reperfusion injury (LIRI by clamping the pulmonary hilum. Twenty Wistar rats were subjected to an experimental model in four groups: SHAM, ischemia-reperfusion (IR, RC-Pre, and RC-Post. The final mean arterial pressure significantly decreased in IR and RC-Pre compared to their values before reperfusion (P<0.001. The RC-Post group showed significant decrease of partial pressure of arterial oxygen at the end of the observation when compared to baseline (P=0.005. Caspase-9 activity was significantly higher in the RC-Post as compared to the other groups (P<0.013. No significant differences were observed in eNOS activity among the groups. The groups RC-Pre and RC-Post did not show any significant decrease in IL-1β (P=0.159 and TNF-α (P=0.260, as compared to IR. The histological score showed no significant differences among the groups. In conclusion, RC-3095 does not demonstrate a protective effect in our LIRI model. Additionally, its use after reperfusion seems to potentiate cell damage, stimulating apoptosis.

  4. Core-shell hybrid liposomal vesicles loaded with panax notoginsenoside: preparation, characterization and protective effects on global cerebral ischemia/reperfusion injury and acute myocardial ischemia in rats

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    Zhang J

    2012-08-01

    Full Text Available Jing Zhang,1,* Xizhen Han,1,* Xiang Li,2 Yun Luo,1 Haiping Zhao,1 Ming Yang,1 Bin Ni,1 Zhenggen Liao11Key Laboratory of Modern Preparation of TCM, Ministry of Education, 2National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, People's Republic of China*These authors contributed equally to this workPurpose: Novel panax notoginsenoside-loaded core-shell hybrid liposomal vesicles (PNS-HLV were developed to resolve the restricted bioavailability of PNS and to enhance its protective effects in vivo on oral administration.Methods: Physicochemical characterizations of PNS-HLV included assessment of morphology, particle size and zeta potential, encapsulation efficiency (EE%, stability and in vitro release study. In addition, to evaluate its oral treatment potential, we compared the effect of PNS-HLV on global cerebral ischemia/reperfusion and acute myocardial ischemia injury with those of PNS solution, conventional PNS-loaded nanoparticles, and liposomes.Results: In comparison with PNS solution, conventional PNS-loaded nanoparticles and liposomes, PNS-HLV was stable for at least 12 months at 4°C. Satisfactory improvements in the EE% of notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 were shown with the differences in EE% shortened and the greater controlled drug release profiles were exhibited from PNS-HLV. The improvements in the physicochemical properties of HLV contributed to the results that PNS-HLV was able to significantly inhibit the edema of brain and reduce the infarct volume, while it could markedly inhibit H2O2, modified Dixon agar, and serum lactate dehydrogenase, and increase superoxide dismutase (P < 0.05.Conclusion: The results of the present study imply that HLV has promising prospects for improving free drug bioactivity on oral administration.Keywords: liposomes, nanoparticles, panax notoginsenoside, physicochemical properties

  5. Ultrasonic tissue characterization with integrated backscatter. Acute myocardial ischemia, reperfusion, and stunned myocardium in patients

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    Milunski, M.R.; Mohr, G.A.; Perez, J.E.; Vered, Z.; Wear, K.A.; Gessler, C.J.; Sobel, B.E.; Miller, J.G.; Wickline, S.A. (Washington Univ., St. Louis, MO (USA))

    1989-09-01

    We have previously shown in studies of experimental animals that myocardium exhibits a cardiac cycle-dependent variation of integrated backscatter that reflects regional myocardial contractile performance and that is blunted promptly after arterial occlusion and recovers after reperfusion. To define the clinical utility of ultrasonic tissue characterization with integrated backscatter for detection of acute myocardial infarction and reperfusion, 21 patients (14 men and seven women) were studied in the cardiac care unit within the first 24 hours (mean time, 11.3 hours; range, 3.5-23.8 hours) after the onset of symptoms indicative of acute myocardial infarction with conventional two-dimensional and M-mode echocardiography and with analysis of integrated backscatter. The magnitude of cyclic variation of integrated backscatter was measured from several sites within acute infarct regions and normal regions remote from the infarct zone for each patient. The average magnitude of cyclic variation among all patients (n = 21) was 4.8 +/- 0.5 dB in normal regions compared with 0.8 +/- 0.3 dB in infarct regions (p less than 0.05) within the first 24 hours after the onset of symptoms. Among the patients who had two studies, 15 (mean, 7.1 days; range, 2-31 days for second study) underwent coronary arteriography to define vessel patency. In patients with vessels with documented patency (n = 10), the magnitude of cyclic variation in infarct regions increased over time from 1.3 +/- 0.6 to 2.5 +/- 0.5 dB from the initial to final study (p less than 0.05). Patients with occluded infarct-related arteries (n = 5) exhibited no significant recovery of cyclic variation (0.3 +/- 0.3-0.6 +/- 0.3 dB). A blinded analysis of standard two-dimensional echocardiographic images revealed no significant recovery of wall thickening in either group over the same time intervals.

  6. Catheter-based Intramyocardial Injection of FGF1 or NRG1-loaded MPs Improves Cardiac Function in a Preclinical Model of Ischemia-Reperfusion

    Science.gov (United States)

    Garbayo, Elisa; Gavira, Juan José; de Yebenes, Manuel Garcia; Pelacho, Beatriz; Abizanda, Gloria; Lana, Hugo; Blanco-Prieto, María José; Prosper, Felipe

    2016-05-01

    Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemia-reperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials.

  7. Fucoidan reduces inflammatory response in a rat model of hepatic ischemia-reperfusion injury.

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    Li, Xiao-Jing; Ye, Qi-Fa

    2015-11-01

    Ischemia-reperfusion (I/R) injury after a liver transplant is a major cause of severe complications that lead to graft dysfunction. Fucoidan, a complex of sulfated polysaccharides derived from marine brown algae, demonstrated antiapoptotic as well as potential anti-inflammatory properties in previous studies. Fucoidan has also shown protective effects on I/R-injured kidney and heart. However, whether fucoidan can attenuate hepatic I/R injury has not been examined. To clarify the role of fucoidan in hepatic I/R injury, Sprague-Dawley rats were subjected to sham operation or ischemia followed by reperfusion with treatment of saline or fucoidan (50, 100, or 200 mg·(kg body mass)(-1)·d(-1)). The fucoidan-treated group showed decreased levels of alanine aminotransferase and aspartate aminotransferase compared with the control group. Myeloperoxidase and malondialdehyde activities and mRNA levels of CD11b in the fucoidan-treated group were significantly decreased. Hepatocellular swelling/necrosis, sinusoidal/vascular congestion, and inflammatory cell infiltration were also attenuated in the fucoidan group. The expression of TNF-α, IL-6, IL-1β, CXCL-10, VCAM-1, and ICAM-1 were markedly decreased in the samples from the fucoidan-treated group. Fucoidan largely prevented activation of the inflammatory signaling pathway, compared with the control group. In summary, fucoidan can protect the liver from I/R injury through suppressing activation of the inflammatory signaling pathway, as well as the expression of inflammatory mediators, and inflammatory cell infiltration.

  8. Oxygen-glucose deprivation and reoxygenation as an in vitro ischemia-reperfusion injury model for studying blood-brain barrier dysfunction.

    Science.gov (United States)

    Alluri, Himakarnika; Anasooya Shaji, Chinchusha; Davis, Matthew L; Tharakan, Binu

    2015-05-07

    Ischemia-Reperfusion (IR) injury is known to contribute significantly to the morbidity and mortality associated with ischemic strokes. Ischemic cerebrovascular accidents account for 80% of all strokes. A common cause of IR injury is the rapid inflow of fluids following an acute/chronic occlusion of blood, nutrients, oxygen to the tissue triggering the formation of free radicals. Ischemic stroke is followed by blood-brain barrier (BBB) dysfunction and vasogenic brain edema. Structurally, tight junctions (TJs) between the endothelial cells play an important role in maintaining the integrity of the blood-brain barrier (BBB). IR injury is an early secondary injury leading to a non-specific, inflammatory response. Oxidative and metabolic stress following inflammation triggers secondary brain damage including BBB permeability and disruption of tight junction (TJ) integrity. Our protocol presents an in vitro example of oxygen-glucose deprivation and reoxygenation (OGD-R) on rat brain endothelial cell TJ integrity and stress fiber formation. Currently, several experimental in vivo models are used to study the effects of IR injury; however they have several limitations, such as the technical challenges in performing surgeries, gene dependent molecular influences and difficulty in studying mechanistic relationships. However, in vitro models may aid in overcoming many of those limitations. The presented protocol can be used to study the various molecular mechanisms and mechanistic relationships to provide potential therapeutic strategies. However, the results of in vitro studies may differ from standard in vivo studies and should be interpreted with caution.

  9. Inflammatory response and pneumocyte apoptosis during lung ischemia-reperfusion injury in an experimental pulmonary thromboembolism model.

    Science.gov (United States)

    Deng, Chaosheng; Zhai, Zhenguo; Wu, Dawen; Lin, Qichang; Yang, Yuanhua; Yang, Minxia; Ding, Haibo; Cao, Xiaoming; Zhang, Qiaoxian; Wang, Chen

    2015-07-01

    Lung ischemia-reperfusion injury (LIRI) may occur in the region of the affected lung after reperfusion therapy. The inflammatory response mechanisms related to LIRI in pulmonary thromboembolism (PTE), especially in chronic PTE, need to be studied further. In a PTE model, inflammatory response and apoptosis may occur during LIRI and nitric oxide (NO) inhalation may alleviate the inflammatory response and apoptosis of pneumocytes during LIRI. A PTE canine model was established through blood clot embolism to the right lower lobar pulmonary artery. Two weeks later, we performed embolectomy with reperfusion to examine the LIRI changes among different groups. In particular, the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), serum concentrations of tumor necrosis factor-α (TNF-α), myeloperoxidase concentrations in lung homogenates, alveolar polymorphonuclear neutrophils (PMNs), lobar lung wet to dry ratio (W/D ratio), apoptotic pneumocytes, and lung sample ultrastructure were assessed. The PaO2/FiO2 in the NO inhalation group increased significantly when compared with the reperfusion group 4 and 6 h after reperfusion (368.83 ± 55.29 vs. 287.90 ± 54.84 mmHg, P inflammatory response and apoptosis occur in our PTE model and NO inhalation may be useful in treating LIRI by alleviating the inflammatory response and pneumocyte apoptosis. This potential application warrants further investigation.

  10. Kaempferol Attenuates Myocardial Ischemic Injury via Inhibition of MAPK Signaling Pathway in Experimental Model of Myocardial Ischemia-Reperfusion Injury

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    Kapil Suchal

    2016-01-01

    Full Text Available Kaempferol (KMP, a dietary flavonoid, has antioxidant, anti-inflammatory, and antiapoptotic effects. Hence, we investigated the effect of KMP in ischemia-reperfusion (IR model of myocardial injury in rats. We studied male albino Wistar rats that were divided into sham, IR-control, KMP-20 + IR, and KMP 20 per se groups. KMP (20 mg/kg; i.p. was administered daily to rats for the period of 15 days, and, on the 15th day, ischemia was produced by one-stage ligation of left anterior descending coronary artery for 45 min followed by reperfusion for 60 min. After completion of surgery, rats were sacrificed; heart was removed and processed for biochemical, morphological, and molecular studies. KMP pretreatment significantly ameliorated IR injury by maintaining cardiac function, normalizing oxidative stress, and preserving morphological alterations. Furthermore, there was a decrease in the level of inflammatory markers (TNF-α, IL-6, and NFκB, inhibition of active JNK and p38 proteins, and activation of ERK1/ERK2, a prosurvival kinase. Additionally, it also attenuated apoptosis by reducing the expression of proapoptotic proteins (Bax and Caspase-3, TUNEL positive cells, and increased level of antiapoptotic proteins (Bcl-2. In conclusion, KMP protected against IR injury by attenuating inflammation and apoptosis through the modulation of MAPK pathway.

  11. Differential protein expression in spinal cord tissue of a rabbit model of spinal cord ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Qi Gao; Jian Dong; Jianhang Jiao; Yonghui Liang; Xiaoyu Yang; Guifeng Liu; Xiaoxue Li; Benqing Zhu; Jian Liu; Maoguang Yang; Weiwei Xia

    2012-01-01

    New Zealand rabbits were randomly divided into an ischemia group (occlusion of the abdominal aorta for 60 minutes), an ischemia-reperfusion group (occlusion of the abdominal aorta for 60 minutes followed by 48 hours of reperfusion) and a sham-surgery group. Two-dimensional gel electrophoresis detected 49 differentially expressed proteins in spinal cord tissue from the ischemia and ischemia/reperfusion groups and 23 of them were identified by mass spectrometry. In the ischemia group, the expression of eight proteins was up regulated, and that of the remaining four proteins was down regulated. In the ischemia/reperfusion group, the expression of four proteins was up regulated, and that of two proteins was down regulated. In the sham-surgery group, only one protein was detected. In the ischemia and ischemia/reperfusion groups, four proteins overlapped between groups with the same differential expression, including three that were up regulated and one down regulated. These proteins were related to energy metabolism, cell defense, inflammatory mechanism and cell signaling.

  12. Quercetin protects rat skeletal muscle from ischemia reperfusion injury.

    Science.gov (United States)

    Ekinci Akdemir, Fazile Nur; Gülçin, İlhami; Karagöz, Berna; Soslu, Recep

    2016-01-01

    In this study, we investigated the potential beneficial effects of quercetin on skeletal muscle ischemia reperfusion injury. Twenty-four Sprague-Dawley type rats were randomly divided into four groups. In the sham group, only gastrocnemius muscle were removed and given no quercetin. In ischemia group, all the femoral artery, vein and collaterals were occluded in the left hindlimb by applying tourniquate under general anaesthesia for three hours but reperfusion was not done. In the Quercetin + Ischemia reperfusion group, quercetin (200 mg kg(-1) dose orally) was given during one-week reoperation and later ischemia reperfusion model was done. Finally, gastrocnemius muscle samples were removed to measure biochemical parameters. The biomarkers, MDA levels, SOD, CAT and GPx activities, were evaluated related to skeletal muscle ischemia reperfusion injury. MDA levels reduced and SOD, CAT and GPx activities increased significantly in Quercetin + Ischemia reperfusion group. Results clearly showed that Quercetin have a protective role against oxidative damage induced by ischemia reperfusion in rats.

  13. Neuroprotective effects of rutaecarpine on cerebral ischemia reperfusion injury**

    Institute of Scientific and Technical Information of China (English)

    Chunlin Yan; Ji Zhang; Shu Wang; Guiping Xue; Yong Hou

    2013-01-01

    Rutaecarpine, an active component of the traditional Chinese medicine Tetradium ruticarpum, has been shown to improve myocardial ischemia reperfusion injury. Because both cardiovascular and cerebrovascular diseases are forms of ischemic vascular disease, they are closely related. We hypothesized that rutaecarpine also has neuroprotective effects on cerebral ischemia reperfusion injury. A cerebral ischemia reperfusion model was established after 84, 252 and 504 µg/kg carpine were given to mice via intraperitoneal injection, daily for 7 days. Results of the step through test, 2,3,5-triphenyl tetrazolium chloride dyeing and oxidative stress indicators showed that rutae-carpine could improve learning and memory ability, neurological symptoms and reduce infarction volume and cerebral water content in mice with cerebral ischemia reperfusion injury. Rutaecarpine could significantly decrease the malondialdehyde content and increase the activities of superoxide dismutase and glutathione peroxidase in mouse brain. Therefore, rutaecarpine could improve neu-rological function fol owing injury induced by cerebral ischemia reperfusion, and the mechanism of this improvement may be associated with oxidative stress. These results verify that rutaecarpine has neuroprotective effects on cerebral ischemia reperfusion in mice.

  14. Ischemia reperfusion dysfunction changes model-estimated kinetics of myofilament interaction due to inotropic drugs in isolated hearts

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    Riess Matthias L

    2006-03-01

    Full Text Available Abstract Background The phase-space relationship between simultaneously measured myoplasmic [Ca2+] and isovolumetric left ventricular pressure (LVP in guinea pig intact hearts is altered by ischemic and inotropic interventions. Our objective was to mathematically model this phase-space relationship between [Ca2+] and LVP with a focus on the changes in cross-bridge kinetics and myofilament Ca2+ sensitivity responsible for alterations in Ca2+-contraction coupling due to inotropic drugs in the presence and absence of ischemia reperfusion (IR injury. Methods We used a four state computational model to predict LVP using experimentally measured, averaged myoplasmic [Ca2+] transients from unpaced, isolated guinea pig hearts as the model input. Values of model parameters were estimated by minimizing the error between experimentally measured LVP and model-predicted LVP. Results We found that IR injury resulted in reduced myofilament Ca2+ sensitivity, and decreased cross-bridge association and dissociation rates. Dopamine (8 μM reduced myofilament Ca2+ sensitivity before, but enhanced it after ischemia while improving cross-bridge kinetics before and after IR injury. Dobutamine (4 μM reduced myofilament Ca2+ sensitivity while improving cross-bridge kinetics before and after ischemia. Digoxin (1 μM increased myofilament Ca2+ sensitivity and cross-bridge kinetics after but not before ischemia. Levosimendan (1 μM enhanced myofilament Ca2+ affinity and cross-bridge kinetics only after ischemia. Conclusion Estimated model parameters reveal mechanistic changes in Ca2+-contraction coupling due to IR injury, specifically the inefficient utilization of Ca2+ for contractile function with diastolic contracture (increase in resting diastolic LVP. The model parameters also reveal drug-induced improvements in Ca2+-contraction coupling before and after IR injury.

  15. Evaluation of the Antioxidant Potential of Salvia miltiorrhiza Ethanol Extract in a Rat Model of Ischemia-Reperfusion Injury

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    Zengyong Qiao

    2011-12-01

    Full Text Available The present study was undertaken to evaluate the protection potential of ethanol extract of Salvia miltiorrhiza (SMEE against oxidative injury in the ischemia-reperfusion (I/R model of rats in vivo. Rats were divided into six groups of 10 rats each. Group I/R model and sham were fed with a standard rat chow, groups SMEE I and SMEE II were fed with a standard rat chow and 400 or 800 mg/kg b.w. ethanol extract for 12 days before the beginning of I/R studies. Positive control group was fed with a standard rat chow and salvianolic acid B (55 mg/kg b.w. or tanshinone II-A (55 mg/kg b.w. for 12 days before the beginning of I/R studies. To produce I/R, the left anterior descending artery (LAD was occluded in anesthetized rats for 15 min, followed by 120 min reperfusion. Infarct sizes were found significantly decreased in SMEE-treated and positive control groups compared to I/R model group. Serum AST, LDH and CK-MB activities were significantly reduced and myocardium Na+-K+ ATPase, Ca2+-Mg2+ ATPase activities and antioxidant enzyme activities (SOD, CAT, GSH-Px were markedly increased in SMEE-treated and salvianolic acid B or tanshinone II-A positive control groups compared to the I/R model group. Pretreatment of S. miltiorrhiza ethanol extract and salvianolic acid B or tanshinone II-A dose-dependently reduced significantly myocardium MDA level, ROS and NOS activities and enhanced myocardium GSH level in I/R rats compared to I/R rats model. In conclusion, we clearly demonstrated that S. miltiorrhiza ethanol extract pretreatment can decrease oxidative injury in rats subjected to myocardial I/R.

  16. Preconditioning with L-alanyl-L-glutamine in a Mongolian Gerbil model of acute cerebral ischemia/reperfusion injury Pré-condicionamento com L-alanil-L-glutamina em modelo de isquemia/reperfusão cerebral aguda em Gerbils da Mongólia

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    Vilma Leite de Sousa Pires

    2011-01-01

    Full Text Available PURPOSE: To investigate the effect of L-alanyl-L-glutamine (L-Ala-Gln preconditioning in an acute cerebral ischemia/reperfusion (I/R model in gerbils. METHODS: Thirty-six Mongolian gerbils (Meriones unguiculatus, (60-100g, were randomized in 2 groups (n=18 and preconditioned with saline 2.0 ml (Group-S or 0.75g/Kg of L-Ala-Gln, (Group-G administered into the femoral vein 30 minutes prior to I/R. Each group was divided into three subgroups (n=6. Anesthetized animals (urethane, 1.5g/Kg, i.p. were submitted to bilateral occlusion of common carotid arteries during 15 minutes. Samples (brain tissue and arterial blood were collected at the end of ischemia (T0 and after 30 (T30 and 60 minutes (T60 for glucose, lactate, myeloperoxidase (MPO, thiobarbituric acid reactive substances (TBARS, glutathione (GSH assays and histopathological evaluation. RESULTS: Glucose and lactate levels were not different in studied groups. However glycemia increased significantly in saline groups at the end of the reperfusion period. TBARS levels were significantly different, comparing treated (Group-G and control group after 30 minutes of reperfusion (pOBJETIVO: Investigar o efeito do pré-condicionamento com L-alanil-L-glutamina (L-Ala-Gln em gerbils submetidos à isquemia/reperfusão (I/R cerebral aguda. MÉTODOS: Trinta e seis gerbils (Meriones unguiculatus (60-100g foram divididos em dois grupos (n=18 e pré-condicionados com 2,0 ml de soro fisiológico (Grupo-S ou 0.75g/kg de L-Ala-Gln, (Grupo-G, administrados na veia femoral 30 minutos antes da I / R. Cada grupo foi dividido em três subgrupos (n=6.Animais anestesiados com uretano, 1.5g/kg, ip, foram submetidos à oclusão bilateral das artérias carótidas comuns, durante 15 minutos. Amostras (tecido cerebral e sangue arterial foram coletadas no final da isquemia (T0 e após 30 (T30 e 60 minutos (T60 para a aferição das concentrações de glicose, lactato, mieloperoxidase (MPO, substâncias reagentes ao

  17. Enalapril protects against myocardial ischemia/reperfusion injury in a swine model of cardiac arrest and resuscitation

    Science.gov (United States)

    Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

    2016-01-01

    There is strong evidence to suggest that angiotensin-converting enzyme inhibitors (ACEIs) protect against local myocardial ischemia/reperfusion (I/R) injury. This study was designed to explore whether ACEIs exert cardioprotective effects in a swine model of cardiac arrest (CA) and resuscitation. Male pigs were randomly assigned to three groups: sham-operated group, saline treatment group and enalapril treatment group. Thirty minutes after drug infusion, the animals in the saline and enalapril groups were subjected to ventricular fibrillation (8 min) followed by cardiopulmonary resuscitation (up to 30 min). Cardiac function was monitored, and myocardial tissue and blood were collected for analysis. Enalapril pre-treatment did not improve cardiac function or the 6-h survival rate after CA and resuscitation; however, this intervention ameliorated myocardial ultrastructural damage, reduced the level of plasma cardiac troponin I and decreased myocardial apoptosis. Plasma angiotensin (Ang) II and Ang-(1–7) levels were enhanced in the model of CA and resuscitation. Enalapril reduced the plasma Ang II level at 4 and 6 h after the return of spontaneous circulation whereas enalapril did not affect the plasma Ang-(1–7) level. Enalapril pre-treatment decreased the myocardial mRNA and protein expression of angiotensin-converting enzyme (ACE). Enalapril treatment also reduced the myocardial ACE/ACE2 ratio, both at the mRNA and the protein level. Enalapril pre-treatment did not affect the upregulation of ACE2, Ang II type 1 receptor (AT1R) and MAS after CA and resuscitation. Taken together, these findings suggest that enalapril protects against ischemic injury through the attenuation of the ACE/Ang II/AT1R axis after CA and resuscitation in pigs. These results suggest the potential therapeutic value of ACEIs in patients with CA. PMID:27633002

  18. Effects of vagus nerve stimulation on cognitive functioning in rats with cerebral ischemia reperfusion

    OpenAIRE

    Liu, Ai-Fen; Zhao, Feng-bo; Wang, Jing; Lu, Yi-Fan; Tian, Jian; Zhao, Yin; Gao, Yan; Hu, Xia-jun; LIU, XIAO-YAN; Tan, Jie; Tian, Yun-li; Shi, Jing

    2016-01-01

    Background Vagus nerve stimulation (VNS) has become the most common non-pharmacological treatment for intractable drug-resistant epilepsy. However, the contribution of VNS to neurological rehabilitation following stroke has not been thoroughly examined. Therefore, we investigated the specific role of acute VNS in the recovery of cognitive functioning and the possible mechanisms involved using a cerebral ischemia/reperfusion (I/R) injury model in rats. Methods The I/R-related injury was modele...

  19. Computed Tomography Perfusion Imaging Detection of Microcirculatory Dysfunction in Small Intestinal Ischemia-Reperfusion Injury in a Porcine Model.

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    Haifeng Shi

    Full Text Available To evaluate multi-slice computed tomography (CT perfusion imaging (CTPI for identifying microcirculatory dysfunction in small intestinal ischemia-reperfusion (IR injury in a porcine model.Fifty-two pigs were randomly divided into 4 groups: (1 the IR group (n = 24, where intestinal ischemia was induced by separating and clamping the superior mesenteric artery (SMA for 2 h, followed by reperfusion for 1, 2, 3, and 4 h (IR-1h, IR-2h, IR-3h, and IR-4h; n = 6, respectively; (2 the sham-operated (SO group (n = 20, where the SMA was separated without clamping and controlled at postoperative 3, 4, 5, and 6 h (SO-3h, SO-4h, SO-5h, and SO-6h; n = 5, respectively; (3 the ischemia group (n = 4, where the SMA was separated and clamped for 2 h, without reperfusion, and (4 baseline group (n = 4, an additional group that was not manipulated. Small intestinal CTPI was performed at corresponding time points and perfusion parameters were obtained. The distal ileum was resected to measure the concentrations of malondialdehyde (MDA and superoxide dismutase (SOD and for histopathological examination.The perfusion parameters of the IR groups showed significant differences compared with the corresponding SO groups and the baseline group (before ischemia. The blood flow (BF, blood volume (BV, and permeability surface (PS among the 4 IR groups were significantly different. BF and BV were significantly negatively correlated with MDA, and significantly positively correlated with SOD in the IR groups. Histopathologically, the effects of the 2-h ischemic loops were not significantly exacerbated by reperfusion.CTPI can be a valuable tool for detecting microcirculatory dysfunction and for dynamic monitoring of small intestinal IR injury.

  20. Renoprotective Mechanism of Remote Ischemic Preconditioning Based on Transcriptomic Analysis in a Porcine Renal Ischemia Reperfusion Injury Model.

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    Young Eun Yoon

    Full Text Available Ischemic preconditioning (IPC is a well-known phenomenon in which tissues are exposed to a brief period of ischemia prior to a longer ischemic event. This technique produces tissue tolerance to ischemia reperfusion injury (IRI. Currently, IPC's mechanism of action is poorly understood. Using a porcine single kidney model, we performed remote IPC with renal IRI and evaluated the IPC mechanism of action. Following left nephrectomy, 15 female Yorkshire pigs were divided into three groups: no IPC and 90 minutes of warm ischemia (control, remote IPC immediately followed by 90 minutes of warm ischemia (rIPCe, and remote IPC with 90 minutes of warm ischemia performed 24 hours later (rIPCl. Differential gene expression analysis was performed using a porcine-specific microarray. The microarray analysis of porcine renal tissues identified 1,053 differentially expressed probes in preconditioned pigs. Among these, 179 genes had altered expression in both the rIPCe and rIPCl groups. The genes were largely related to oxidation reduction, apoptosis, and inflammatory response. In the rIPCl group, an additional 848 genes had altered expression levels. These genes were primarily related to immune response and inflammation, including those coding for cytokines and cytokine receptors and those that play roles in the complement system and coagulation cascade. In the complement system, the membrane attack complex was determined to be sublytic, because it colocalized with phosphorylated extracellular signal-regulated kinase. Furthermore, alpha 2 macroglobulin, tissue plasminogen activator, uterine plasmin trypsin inhibitor, and arginase-1 mRNA levels were elevated in the rIPCl group. These findings indicate that remote IPC produces renoprotective effects through multiple mechanisms, and these effects develop over a long timeframe rather than immediately following IPC.

  1. Postconditioning with inhaled hydrogen promotes survival of retinal ganglion cells in a rat model of retinal ischemia/reperfusion injury.

    Science.gov (United States)

    Wang, Ruobing; Wu, Jiangchun; Chen, Zeli; Xia, Fangzhou; Sun, Qinglei; Liu, Lin

    2016-02-01

    Retinal ischemia/reperfusion (I/R) injury plays a crucial role in the pathophysiology of various ocular diseases. Intraperitoneal injection or ocular instillation with hydrogen (H2)-rich saline was recently shown to be neuroprotective in the retina due to its anti-oxidative and anti-inflammatory effects. Our study aims to explore whether postconditioning with inhaled H2 can protect retinal ganglion cells (RGCs) in a rat model of retinal I/R injury. Retinal I/R injury was performed on the right eyes of rats and was followed by inhalation of 67% H2 mixed with 33% oxygen immediately after ischemia for 1h daily for one week. RGC density was counted using haematoxylin and eosin (HE) staining and retrograde labeling with cholera toxin beta (CTB). Visual function was assessed using flash visual evoked potentials (FVEP) and pupillary light reflex (PLR). Potential biomarkers of retinal oxidative stress and inflammatory responses were measured, including the expression of 4-Hydroxynonenalv (4-HNE), interleukin-1 beta (IL1-β) and tumor necrosis factor alpha (TNF-α). HE and CTB tracing showed that the survival rate of RGCs in the H2-treated group was significantly higher than the rate in the I/R group. Rats with H2 inhalation showed better visual function in assessments of FVEP and PLR. Moreover, H2 treatment significantly decreased the number of 4-HNE-stained cells in the ganglion cell layer and inhibited the retinal overexpression of IL1-β and TNF-α that was induced by retinal I/R injury. Our results demonstrate that postconditioning with inhaled high-dose H2 appears to confer neuroprotection against retinal I/R injury via anti-oxidative, anti-inflammatory and anti-apoptosis pathways.

  2. Aged Garlic Extract Attenuates Neuronal Injury in a Rat Model of Spinal Cord Ischemia/Reperfusion Injury.

    Science.gov (United States)

    Cemil, Berker; Gokce, Emre Cemal; Kahveci, Ramazan; Gokce, Aysun; Aksoy, Nurkan; Sargon, Mustafa Fevzi; Erdogan, Bulent; Kosem, Bahadir

    2016-06-01

    Garlic has been used as a food as well as a component of traditional medicine. Aged garlic extract (AGE) is claimed to promote human health through antioxidant/anti-inflammatory activities with neuroprotective effects. We evaluated the possible beneficial effect of AGE neurologically, pathologically, ultrastructurally, and biochemically in a spinal cord ischemia-reperfusion (I/R) model of rats. Twenty-four Sprague-Dawley rats were divided into three groups: sham (no I/R), I/R, and AGE (I/R+AGE); each group consisted of eight animals. Animals were evaluated neurologically with the Basso, Beattie, and Bresnahan (BBB) scoring system. The spinal cord tissue samples were harvested for pathological and ultrastructural examinations. Oxidative products (Malondialdehyde, nitric oxide), antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase), inflammatory cytokines (tissue tumor necrosis factor alpha, interleukin-1), and caspase-3 activity were analyzed. The AGE group had significantly higher BBB scores than the I/R group. Pathologically, AGE group revealed reduced degree of ischemia and spinal cord edema. Ultrastructural results also showed preservation of tissue structure in the AGE group. Oxidative product levels of the I/R group were significantly higher than both the other groups, and antioxidant enzyme levels of AGE group were significantly higher than the I/R group. There was also significant difference between the sham and AGE groups in terms of total antioxidant enzyme levels. Furthermore, AGE treatment significantly reduced the inflammatory cytokines and caspase-3 activity than the I/R group. This study demonstrates the considerable neuroprotective effect of AGE on the neurological, pathological, ultrastructural, and biochemical status of rats with I/R-induced spinal cord injury.

  3. Electroacupuncture stimulation of the brachial plexus trunk on the healthy side promotes brain-derived neurotrophic factor mRNA expression in the ischemic cerebral cortex of a rat model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Zongjun Guo; Lumin Wang

    2012-01-01

    A rat model of cerebral ischemia/reperfusion was established by suture occlusion of the left middle cerebral artery. In situ hybridization results showed that the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic rat cerebral cortex increased after cerebral ischemia/ reperfusion injury. Low frequency continuous wave electroacupuncture (frequency 2-6 Hz, current intensity 2 mA) stimulation of the brachial plexus trunk on the healthy (right) side increased the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic cerebral cortex 14 days after cerebral ischemia/reperfusion injury. At the same time, electroacupuncture stimulation of the healthy brachial plexus truck significantly decreased neurological function scores and alleviated neurological function deficits. These findings suggest that electroacupuncture stimulation of the brachial plexus trunk on the healthy (right) side can greatly increase brain-derived neurotrophic factor mRNA expression and improve neurological function.

  4. Electroacupuncture stimulation of the brachial plexus trunk on the healthy side promotes brain-derived neurotrophic factor mRNA expression in the ischemic cerebral cortex of a rat model of cerebral ischemia/reperfusion injury.

    Science.gov (United States)

    Guo, Zongjun; Wang, Lumin

    2012-07-25

    A rat model of cerebral ischemia/reperfusion was established by suture occlusion of the left middle cerebral artery. In situ hybridization results showed that the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic rat cerebral cortex increased after cerebral ischemia/ reperfusion injury. Low frequency continuous wave electroacupuncture (frequency 2-6 Hz, current intensity 2 mA) stimulation of the brachial plexus trunk on the healthy (right) side increased the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic cerebral cortex 14 days after cerebral ischemia/reperfusion injury. At the same time, electroacupuncture stimulation of the healthy brachial plexus truck significantly decreased neurological function scores and alleviated neurological function deficits. These findings suggest that electroacupuncture stimulation of the brachial plexus trunk on the healthy (right) side can greatly increase brain-derived neurotrophic factor mRNA expression and improve neurological function.

  5. Inhibition of Fas-associated death domain-containing protein (FADD protects against myocardial ischemia/reperfusion injury in a heart failure mouse model.

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    Qian Fan

    Full Text Available AIM: As technological interventions treating acute myocardial infarction (MI improve, post-ischemic heart failure increasingly threatens patient health. The aim of the current study was to test whether FADD could be a potential target of gene therapy in the treatment of heart failure. METHODS: Cardiomyocyte-specific FADD knockout mice along with non-transgenic littermates (NLC were subjected to 30 minutes myocardial ischemia followed by 7 days of reperfusion or 6 weeks of permanent myocardial ischemia via the ligation of left main descending coronary artery. Cardiac function were evaluated by echocardiography and left ventricular (LV catheterization and cardiomyocyte death was measured by Evans blue-TTC staining, TUNEL staining, and caspase-3, -8, and -9 activities. In vitro, H9C2 cells transfected with ether scramble siRNA or FADD siRNA were stressed with chelerythrin for 30 min and cleaved caspase-3 was assessed. RESULTS: FADD expression was significantly decreased in FADD knockout mice compared to NLC. Ischemia/reperfusion (I/R upregulated FADD expression in NLC mice, but not in FADD knockout mice at the early time. FADD deletion significantly attenuated I/R-induced cardiac dysfunction, decreased myocardial necrosis, and inhibited cardiomyocyte apoptosis. Furthermore, in 6 weeks long term permanent ischemia model, FADD deletion significantly reduced the infarct size (from 41.20 ± 3.90% in NLC to 26.83 ± 4.17% in FADD deletion, attenuated myocardial remodeling, improved cardiac function and improved survival. In vitro, FADD knockdown significantly reduced chelerythrin-induced the level of cleaved caspase-3. CONCLUSION: Taken together, our results suggest FADD plays a critical role in post-ischemic heart failure. Inhibition of FADD retards heart failure progression. Our data supports the further investigation of FADD as a potential target for genetic manipulation in the treatment of heart failure.

  6. Intestinal ischemia/reperfusion induces bronchial hyperreactivity and increases serum TNF-alpha in rats

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    Arruda Marcio Jose Cristiano de

    2006-01-01

    Full Text Available INTRODUCTION: Intestinal or hepatic ischemia/reperfusion induces acute lung injury in animal models of multiple organ failure. Tumor necrosis factor (TNF- alpha is involved in the underlying inflammatory mechanism of acute respiratory distress syndrome. Although the inflammatory cascade leading to acute respiratory distress syndrome has been extensively investigated, the mechanical components of acute respiratory distress syndrome are not fully understood. Our hypothesis is that splanchnic ischemia/reperfusion increases airway reactivity and serum TNF-alpha levels. OBJECTIVE: To assess bronchial smooth muscle reactivity under methacholine stimulation, and to measure serum TNF-alpha levels following intestinal and/or hepatic ischemia/reperfusion in rats. METHOD: Rats were subjected to 45 minutes of intestinal ischemia, or 20 minutes of hepatic ischemia, or to both (double ischemia, or sham procedures (control, followed by 120 minutes of reperfusion. The animals were then sacrificed, and the bronchial response to increasing methacholine molar concentrations (10-7 to 3 x 10-4 was evaluated in an ex-vivo bronchial muscle preparation. Serum TNF-alpha was determined by the L929-cell bioassay. RESULTS: Bronchial response (g/100 mg tissue showed increased reactivity to increasing methacholine concentrations in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. Similarly, serum TNF-alpha (pg/mL concentration was increased in the intestinal ischemia and double ischemia groups, but not in the hepatic ischemia group. CONCLUSION: Intestinal ischemia, either isolated or associated with hepatic ischemia, increased bronchial smooth muscle reactivity, suggesting a possible role for bronchial constriction in respiratory dysfunction following splanchnic ischemia/reperfusion. This increase occurred in concomitance with serum TNF-alpha increase, but whether the increase in TNF-alpha caused this bronchial contractility remains

  7. Evaluation of kidney repair capacity using 99mTc-DMSA in ischemia/reperfusion injury models.

    Science.gov (United States)

    Kwak, Wonjung; Jang, Hee-Seong; Belay, Takele; Kim, Jinu; Ha, Yeong Su; Lee, Sang Woo; Ahn, Byeong-Cheol; Lee, Jaetae; Park, Kwon Moo; Yoo, Jeongsoo

    2011-03-01

    Quantitative (99m)Tc-DMSA renal uptake was studied in different renal ischemia/reperfusion (I/R) mice models for the assessment of renal repair capacity. Mice models of nephrectomy, uni- and bi-lateral I/R together with sham-operated mice were established. At 1h, 1d, 4d, 1, 2 and 3 wk after I/R, (99m)Tc-DMSA (27.7 ± 1.3 MBq) was injected via tail vein and after 3h post-injection, the mice were scanned for 30 min with pinhole equipped gamma camera. Higher uptake of (99m)Tc-DMSA was measured in normal kidneys of uni-lateral I/R model and nephrectomized kidney I/R model at 3 wk post-surgery. Comparing the restoration capacities of the affected kidneys of nephrectomy, uni- and bi-lateral I/R models, higher repair capacity was observed in the nephrectomized model followed by bi-lateral then uni-lateral models. The normal kidney may retard the restoration of damaged kidney in uni-lateral I/R model. Moreover, 3 wk after Uni-I/R, the size of injured kidney was significantly smaller than non-ischemic contralateral and sham operated kidneys, while nephrectomy I/R kidneys were significantly enlarged compared to all others at 3 wk post-surgery. Very strong correlation between (99m)Tc-DMSA uptake and weight of dissected kidneys in I/R models was observed. Consistent with (99m)Tc-DMSA uptake results, all histological results indicate that kidney recovery after injury is correlated with the amount of intact tubules and kidney sizes. In summary, our study showed good potentials of (99m)Tc-DMSA scan as a promising non-invasive method for evaluation of kidney restoration after I/R injuries. Interestingly, mice with Bi-I/R injury showed faster repair capacity than those with uni-I/R.

  8. Delayed contrast enhancement imaging of a murine model for ischemia reperfusion with carbon nanotube micro-CT.

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    Laurel M Burk

    Full Text Available We aim to demonstrate the application of free-breathing prospectively gated carbon nanotube (CNT micro-CT by evaluating a myocardial infarction model with a delayed contrast enhancement technique. Evaluation of murine cardiac models using micro-CT imaging has historically been limited by extreme imaging requirements. Newly-developed CNT-based x-ray sources offer precise temporal resolution, allowing elimination of physiological motion through prospective gating. Using free-breathing, cardiac-gated CNT micro-CT, a myocardial infarction model can be studied non-invasively and with high resolution. Myocardial infarction was induced in eight male C57BL/6 mice aged 8-12 weeks. The ischemia reperfusion model was achieved by surgically occluding the LAD artery for 30 minutes followed by 24 hours of reperfusion. Tail vein catheters were placed for contrast administration. Iohexol 300 mgI/mL was administered followed by images obtained in diastole. Iodinated lipid blood pool contrast agent was then administered, followed with images at systole and diastole. Respiratory and cardiac signals were monitored externally and used to gate the scans of free-breathing subjects. Seven control animals were scanned using the same imaging protocol. After imaging, the heart was harvested, cut into 1mm slices and stained with TTC. Post-processing analysis was performed using ITK-Snap and MATLAB. All animals demonstrated obvious delayed contrast enhancement in the left ventricular wall following the Iohexol injection. The blood pool contrast agent revealed significant changes in cardiac function quantified by 3-D volume ejection fractions. All subjects demonstrated areas of myocardial infarct in the LAD distribution on both TTC staining and micro-CT imaging. The CNT micro-CT system aids straightforward, free-breathing, prospectively-gated 3-D murine cardiac imaging. Delayed contrast enhancement allows identification of infarcted myocardium after a myocardial ischemic

  9. Effects of intracoronary melatonin on ischemia-reperfusion injury in ST-elevation myocardial infarction

    DEFF Research Database (Denmark)

    Ekeløf, Sarah V; Halladin, Natalie L; Jensen, Svend E

    2016-01-01

    Acute coronary occlusion is effectively treated by primary percutaneous coronary intervention. However, myocardial ischemia-reperfusion injury is at the moment an unavoidable consequence of the procedure. Oxidative stress is central in the development of ischemia-reperfusion injury. Melatonin......, an endogenous hormone, acts through antioxidant mechanisms and could potentially minimize the myocardial injury. The aim of the experimental study was to examine the cardioprotective effects of melatonin in a porcine closed-chest reperfused infarction model. A total of 20 landrace pigs were randomized...... to a dosage of 200 mg (0.4 mg/mL) melatonin or placebo (saline). The intervention was administered intracoronary and intravenous. Infarct size, area at risk and microvascular obstruction were determined ex vivo by cardiovascular magnetic resonance imaging. Myocardial salvage index was calculated. The plasma...

  10. Pressure Combined with Ischemia/Reperfusion Injury Induces Deep Tissue Injury via Endoplasmic Reticulum Stress in a Rat Pressure Ulcer Model.

    Science.gov (United States)

    Cui, Fei-Fei; Pan, Ying-Ying; Xie, Hao-Huang; Wang, Xiao-Hui; Shi, Hong-Xue; Xiao, Jian; Zhang, Hong-Yu; Chang, Hao-Teng; Jiang, Li-Ping

    2016-02-25

    Pressure ulcer is a complex and significant health problem in long-term bedridden patients, and there is currently no effective treatment or efficient prevention method. Furthermore, the molecular mechanisms and pathogenesis contributing to the deep injury of pressure ulcers are unclear. The aim of the study was to explore the role of endoplasmic reticulum (ER) stress and Akt/GSK3β signaling in pressure ulcers. A model of pressure-induced deep tissue injury in adult Sprague-Dawley rats was established. Rats were treated with 2-h compression and subsequent 0.5-h release for various cycles. After recovery, the tissue in the compressed regions was collected for further analysis. The compressed muscle tissues showed clear cellular degenerative features. First, the expression levels of ER stress proteins GRP78, CHOP, and caspase-12 were generally increased compared to those in the control. Phosphorylated Akt and phosphorylated GSK3β were upregulated in the beginning of muscle compression, and immediately significantly decreased at the initiation of ischemia-reperfusion injury in compressed muscles tissue. These data show that ER stress may be involved in the underlying mechanisms of cell degeneration after pressure ulcers and that the Akt/GSK3β signal pathway may play an important role in deep tissue injury induced by pressure and ischemia/reperfusion.

  11. 5′-Adenosine Monophosphate-Induced Hypothermia Attenuates Brain Ischemia/Reperfusion Injury in a Rat Model by Inhibiting the Inflammatory Response

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    Yi-Feng Miao

    2015-01-01

    Full Text Available Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5′-adenosine monophosphate (5′-AMP, a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5′-AMP-induced hypothermia (AIH may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9, interleukin-1 receptor (IL-1R, tumor necrosis factor receptor (TNFR, and Toll-like receptor (TLR protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL- positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5′-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia.

  12. Role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning

    Institute of Scientific and Technical Information of China (English)

    Kai Sun; Zhi-Su Liu; Quan Sun

    2004-01-01

    AIM: To investigate the role of mitochondria in cell apoptosis during hepatic ischemia-reperfusion injury and protective effect of ischemic postconditioning (IPC).METHODS: A rat model of acute hepatic ischemia-reperfusion was established, 24 healthy male Wistar rats were randomly divided into sham-operated group, ischemia-reperfusion group (IR) and IPC group. IPC was achieved by several brief pre-reperfusions followed by a persistent reperfusion.Concentration of malondialdehyde (MDA) and activity of several antioxidant enzymes in hepatic tissue were measured respectively. Apoptotic cells were detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and expression of Bcl-2 protein was measured by immunohistochemical techniques. Moreover, mitochondrial ultrastructure and parameters of morphology of the above groups were observed by electron microscope.RESULTS: Compared with IR group, the concentration of MDA and the hepatocellular apoptotic index in IPC group was significantly reduced (P<0.05), while the activity of antioxidant enzymes and OD value of Bcl-2 protein were markedly enhanced (P<0.05). Moreover, the injury of mitochondrial ultrastructure in IPC group was also obviously relieved.CONCLUSION: IPC can depress the synthesis of oxygen free radicals to protect the mitochondrial ultrastructure and increase the expression of Bcl-2 protein that lies across the mitochondrial membrane. Consequently, IPC can reduce hepatocellular apoptosis after reperfusion and has a protective effect on hepatic ischemia-reperfusion injury.

  13. Minocycline inhibits neuroinflammation and enhances vascular endothelial growth factor expression in a cerebral ischemia/reperfusion rat model

    Institute of Scientific and Technical Information of China (English)

    Zhiyou Cai; Yong Yan; Changyin Yu; Jun Zhang

    2008-01-01

    BACKGROUND: Brain ischemia involves secondary inflammation, which significantly contributes to the outcome of ischemic insults. Vascular endothelial growth factor (VEGF) may play an important role in the vascular response to cerebral ischemia, because ischemia stimulates VEGF expression in the brain, and VEGF promotes formation of new cerebral blood vessels. Minocyclinc, a tetracycline derivative, protects against cerebral ischemia and reduces inflammation, oxidative stress, and apoptosis.OBJECTIVE: To observe the influence of minocycline on VEGE interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) expression in Wistar rats with focal cerebral ischemia/rcperfusion injury, and to study the neuroproteetion mechanism of minocycline against focal cerebral ischemia/rcpeffusion injury.DESIGN, TIME AND SETTING: Randomized, controlled experiment, which was performed in the Chongqing Key Laboratory of Neurology between March 2007 and March 2008.MATERIALS: A total of 36 female, Wistar rats underwent surgery to insert a thread into the left middle cerebral artery. Animals were randomly divided into sham-operation, minocyclinc treatment, and ischemia/reperfusion groups, with 12 rats in each group. Minocycline (Huishi Pharmaceutical Limited Company, China) was dissolved to 0.5 g/L in normal saline.METHODS: A 0.5- 1.0 cm thread was inserted into rats from the sham-operation group. Rats in the ischemia/reperfusion group underwent ischemia and reperfusion. The minocycline group received minocycline (50 mg/kg) 12 and 24 hours following ischemia and reperfusion, whereas the other groups received saline at the corresponding time points.MAIN OUTCOME MEASURES: mRNA and protein expression of IL-1β and TNF-α was measured by reverse transcriptase-polymerasc chain reaction (RT-PCR) and enzyme linked immunosorbent assay (ELISA), respectively. VEGF mRNA and protein expression was examined by RT-PCR, Western blot, and ELISA.RESULTS: Minocycline decreased the focal infarct

  14. The effect of propofol postconditioning on the expression of K(+)-Cl(-)-co-transporter 2 in GABAergic inhibitory interneurons of acute ischemia/reperfusion injury rats.

    Science.gov (United States)

    Wang, Hongbai; Liu, Shuying; Wang, Haiyun; Wang, Guolin; Zhu, Ai

    2015-02-09

    It has been shown in our previous study that propofol postconditioning enhanced the activity of phosphatidylinositol-3-kinase (PI3K) and prevented the internalization of GluR2 subunit of α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, thus provided neuroprotection in cerebral ischemia/reperfusion (I/R) injury. Regarding inhibitory system in CNS, K(+)-Cl(-)-co-transporter 2 (KCC2), a Cl(-) extruder, plays a critical role in gamma-aminobutyric acid (GABA) inhibitory effect in mature central neurons. However, the effect of propofol postconditioning on the expression of KCC2 in GABAergic interneurons is unclear. Therefore, in this article we describe the role of KCC2 in GABAergic interneurons in the ipsilateral hippocampal CA1 region of adult rats and the effects of propofol postconditioning on this region. Herein we demonstrate that propofol postconditioning (20mg/kg/h, 2h) improved rats' neurobehavioral abilities, increased the number of survival neurons, and up-regulated neuronal KCC2 expression in glutamic acid decarboxylase 67 (GAD67) expressing GABAergic interneurons in hippocampal CA1 region at 24h after I/R. In contrast, when rats were injected with the KCC2 antagonist, [(dihydroindenyl)oxy] alkanoic acid (DIOA), the neuroprotective effects induced by propofol postconditioning were reversed. Our study indicated that propofol postconditioning increased the expression of KCC2 in inhibitory GABAergic interneurons, thus providing acute neuroprotection to rats who had undergone cerebral I/R injury.

  15. Intraperitoneal Bilirubin Administration Decreases Infarct Area in a Rat Coronary Ischemia/Reperfusion Model

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    Ron eBen-Amotz

    2014-02-01

    Full Text Available Bilirubin was previously considered a toxin byproduct of heme catabolism. However, a mounting body of evidence suggests that at physiological doses, bilirubin is a powerful antioxidant and anti-atherosclerotic agent. Recent clinical studies have shown that human beings with genetically-induced hyperbilirubinemia (Gilbert Syndrome are protected against coronary heart disease. The purpose of this study was to investigate whether administration of exogenous bilirubin to normal rats would convey similar protective effects in an experimental model of coronary ischemia. We hypothesized that intraperitoneal bilirubin administration 1 hour before injury would decrease infarct area and preserve left ventricular (LV systolic function when compared to non-treated rats. Coronary ischemia was induced by temporary (30 min ligation of the left anterior descending coronary artery in control or bilirubin treated rats, followed by a 1-hour period of reperfusion. LV function was estimated by measurements of fractional shortening and fractional area shortening using echocardiography. LV function decreased in both experimental groups after ischemia and reperfusion, although in bilirubin-treated rats fractional shortening was less depressed during the period of ischemia (18.8 vs 25.8%, p = 0.034. Infarct size was significantly reduced in the bilirubin treated group compared to the non-treated group (13.34% vs 25.5%, p = 0.0067. Based on the results of this study, bilirubin supplementation appears to provide significant decrease in infarct size although protective effects on LV function were noted only during the period of ischemia. This result also suggests that lipid soluble antioxidant bilirubin prevents the oxidation of cardiolipin and decreases the infarct size in the heart during ischemia.

  16. Mangafodipir protects against hepatic ischemia-reperfusion injury in mice.

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    Romain Coriat

    Full Text Available INTRODUCTION AND AIM: Mangafodipir is a contrast agent used in magnetic resonance imaging that concentrates in the liver and displays pleiotropic antioxidant properties. Since reactive oxygen species are involved in ischemia-reperfusion damages, we hypothesized that the use of mangafodipir could prevent liver lesions in a mouse model of hepatic ischemia reperfusion injury. Mangafodipir (MnDPDP was compared to ischemic preconditioning and intermittent inflow occlusion for the prevention of hepatic ischemia-reperfusion injury in the mouse. METHODS: Mice were subjected to 70% hepatic ischemia (continuous ischemia for 90 min. Thirty minutes before the ischemic period, either mangafodipir (10 mg/kg or saline was injected intraperitoneally. Those experimental groups were compared with one group of mice preconditioned by 10 minutes' ischemia followed by 15 minutes' reperfusion, and one group with intermittent inflow occlusion. Hepatic ischemia-reperfusion injury was evaluated by measurement of serum levels of aspartate aminotransferase (ASAT activity, histologic analysis of the livers, and determination of hepatocyte apoptosis (cytochrome c release, caspase 3 activity. The effect of mangafodipir on the survival rate of mice was studied in a model of total hepatic ischemia. RESULTS: Mangafodipir prevented experimental hepatic ischemia-reperfusion injuries in the mouse as indicated by a reduction in serum ASAT activity (P<0.01, in liver tissue damages, in markers of apoptosis (P<0.01, and by higher rates of survival in treated than in untreated animals (P<0.001. The level of protection by mangafodipir was similar to that observed following intermittent inflow occlusion and higher than after ischemic preconditioning. CONCLUSIONS: Mangafodipir is a potential new preventive treatment for hepatic ischemia-reperfusion injury.

  17. Cardioprotective Effects of Total Flavonoids Extracted from Xinjiang Sprig Rosa rugosa against Acute Ischemia/Reperfusion-Induced Myocardial Injury in Isolated Rat Heart.

    Science.gov (United States)

    Hou, Xuejiao; Han, Jichun; Yuan, Changsheng; Ren, Huanhuan; Zhang, Ya; Zhang, Tao; Xu, Lixia; Zheng, Qiusheng; Chen, Wen

    2016-01-01

    This study evaluated the antioxidative and cardioprotective effects of total flavonoids extracted from Xinjiang sprig Rosa rugosa on ischemia/reperfusion (I/R) injury using an isolated Langendorff rat heart model. The possible mechanism of Xinjiang sprig rose total flavonoid (XSRTF) against I/R injury was also studied. XSRTF (5, 10, and 20 µg/mL) dissolved in Krebs-Henseleit buffer was administered to isolated rat heart. The XSRTF showed remarkable scavenging effects against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl, and superoxide anion radicals in vitro. XSRTF pretreatment improved the heart rate, increased LVDP, and decreased CK and LDH levels in coronary flow. This pretreatment also increased SOD activity and GSH/GSSG ratio but decreased MDA, TNF-α, and CRP levels and IL-8 and IL-6 activities. The infarct size and cell apoptosis in the hearts from the XSRTF-treated group were lower than those in the hearts from the I/R group. Therefore, the cardioprotective effects of XSRTF may be attributed to its antioxidant, antiapoptotic, and anti-inflammatory activities.

  18. Effectiveness of Panax ginseng on Acute Myocardial Ischemia Reperfusion Injury Was Abolished by Flutamide via Endogenous Testosterone-Mediated Akt Pathway.

    Science.gov (United States)

    Pei, Luo; Shaozhen, Hou; Gengting, Dong; Tingbo, Chen; Liang, Liu; Hua, Zhou

    2013-01-01

    Mechanisms for Panax ginseng's cardioprotective effect against ischemia reperfusion injury involve the estrogen-mediated pathway, but little is known about the role of androgen. A standardized Panax ginseng extract (RSE) was orally given with or without flutamide in a left anterior descending coronary artery ligation rat model. Infarct size, CK and LDH activities were measured. Time-related changes of NO, PI3K/Akt/eNOS signaling, and testosterone concentration were also investigated. RSE (80 mg/kg) significantly inhibited myocardial infarction and CK and LDH activities, while coadministration of flutamide abolished this effect of RSE. NO was increased by RSE and reached a peak after 15 min of ischemia; however, flutamide cotreatment suppressed this elevation. Western blot analysis showed that RSE significantly reversed the decreases of expression and activation of PI3K, Akt, and eNOS evoked by ischemia, whereas flutamide attenuated the effects of these protective mechanisms induced by RSE. RSE completely reversed the dropping of endogenous testosterone level induced by I/R injury. Flutamide plus RSE treatment not only abolished RSE's effect but also produced a dramatic change on endogenous testosterone level after pretreatment and ischemia. Our results for the first time indicate that blocking androgen receptor abolishes the ability of Panax ginseng to protect the heart from myocardial I/R injury.

  19. Effects of Chuanxiongqin hydrochloride on increasing the fluidity of brain cell membrane and scavenging free radicals in model rats with ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Chenxu Li

    2006-01-01

    BACKGROUND: The fluidity of cell membrane can be affected by various factors. Many experiments have confirmed that the ischemia/reperfusion of organic tissue can increase the contents of free radicals, which lead to high rigidity and Iow fluidity of cell membrane, and the conditions can be changed by Chuanxiongqin.OBJECTIVE: To observe the effect and mechanism of Chuanxiongqin hydrochloride on the fluidity of brain cell membrane in rat models of ischemia/reperfusion.DESIGN: A completely randomized controlled animal trial.SETTINGS: Institute of Brain Sciences; Department of Physiology, Medical College, Datong University.MATERIALS: Twenty male grade I Wistar rats of 170-220 g were randomly divided into model group (n =10)and control group (n =10). Chuanxiongqin hydrochloride (molecular mass was 172.2) was purchased from the National Institute for the Control of Pharmaceutical and Biological Products (batch number; 0817-9803); Spin labelers: 5-cfoxyl-stearlic acid methylester (5DS), 16-doxyl-stearlic acid methylester (16DS), xanthine, xanthine oxidase (XOD) and 5,5-dimeth-1-pyrroline- N-oxide (DMPO) from Sigma Company; Bruker ESP 300 electron paramagnetic resonance (EPR) spectrometer by Bruker Company (Germany).METHODS: The experiments were carried out in the State Key Laboratory of Natural and Biomimetic Drugs,Peking University from June 2001 to July 2002. In the model group, rats were made into models of cerebral ischemia by 30-minute ligation and 2-hour reperfusion of common carotid arteries; The rats in the control group were not made into models. The order parameter (S) and rotational correlation time (тc) were detected with the ESR spectrometer by means of spin labeling. The greater the S and тc, the smaller the fluidity. Meanwhile, the clearance rate of free radicals was detected with ESR spin trapping. The measurement data were compared using the ttest.MAIN OUTCOME MEASURES: The S, тc and clearance rates of O2 and OH free radicals were compared between the

  20. Effects and Mechanism of Action of Inducible Nitric Oxide Synthase on Apoptosis in a Rat Model of Cerebral Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Zheng, Li; Ding, Junli; Wang, Jianwei; Zhou, Changman; Zhang, Weiguang

    2016-02-01

    Inducible nitric oxide synthase (iNOS) is a key enzyme in regulating nitric oxide (NO) synthesis under stress, and NO has varying ability to regulate apoptosis. The aim of this study was to investigate the effects and possible mechanism of action of iNOS on neuronal apoptosis in a rat model of cerebral focal ischemia and reperfusion injury in rats treated with S-methylisothiourea sulfate (SMT), a high-selective inhibitor of iNOS. Seventy-two male Sprague-Dawley (SD) rats were randomly divided into three groups: the sham, middle cerebral artery occlusion (MCAO) + vehicle, and MCAO + SMT groups. Neurobehavioral deficits, infarct zone size, and cortical neuron morphology were evaluated through the modified Garcia scores, 2,3,5-triphenyltetrazolium chloride (TTC), and Nissl staining, respectively. Brain tissues and serum samples were collected at 72 hr post-reperfusion for immunohistochemical analysis, Western blotting, Terminal deoxynucleotidyl transferase-mediated dUTP-biotin Nick End Labeling assay (TUNEL) staining, and enzyme assays. The study found that inhibition of iNOS significantly attenuated the severity of the pathological changes observed as a result of ischemia-reperfusion injury: SMT reduced NO content as well as total nitric oxide synthase (tNOS) and iNOS activities in both ischemic cerebral hemisphere and serum, improved neurobehavioral scores, reduced mortality, reduced the infarct volume ratio, attenuated morphological changes in cortical neurons, decreased the rate of apoptosis (TUNEL and caspase-3-positive), and increased phospho (p)-AKT expression in ischemic penumbra. These results suggested that inhibition of iNOS might reduce the severity of ischemia-reperfusion injury by inhibiting neuronal apoptosis via maintaining p-AKT activity.

  1. A single intracoronary injection of midkine reduces ischemia/reperfusion injury in swine hearts: a novel therapeutic approach for acute coronary syndrome

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    Hisaaki eIshiguro

    2011-06-01

    Full Text Available Several growth factors are effective for salvaging myocardium and limiting infarct size in experimental studies with small animals. Their benefit in large animals and feasibility in clinical practice remains to be elucidated. We investigate the cardioprotective effect of midkine (MK in swine subjected to ischemia/reperfusion (I/R. I/R was created in swine by left anterior descending coronary artery occlusion for 45 min using a percutaneous over-the-wire balloon catheter. MK protein was injected as a bolus through the catheter at the initiation of reperfusion (midkine injected group; MKT. Saline was injected in controls (CONT. Survival rate 24h after I/R was significantly higher in MKT than in CONT, whereas infarct size/area at risk was almost 5 times smaller. Echocardiography in MKT revealed a significantly higher percent wall thickening of the interventricular septum, a higher % fractional shortening and a lower E/e’ compared with CONT. LV catheterization in MKT showed a lower LVEDP, and a higher dP/dtmax compared with CONT. TUNEL-positive myocytes and CD45-positive cell infiltration in the peri-infarct area were significantly less in MKT than in CONT. Here, we showed that a single intracoronary injection of MK protein in swine hearts at the onset of reperfusion dramatically reduces infarct size and mortality and ameliorates systolic/diastolic LV function. This beneficial effect is associated with a reduction of apoptotic and inflammatory reactions. MK application during percutaneous coronary intervention may become a promising adjunctive therapy in acute coronary syndromes.

  2. A single intracoronary injection of midkine reduces ischemia/reperfusion injury in Swine hearts: a novel therapeutic approach for acute coronary syndrome.

    Science.gov (United States)

    Ishiguro, Hisaaki; Horiba, Mitsuru; Takenaka, Hiroharu; Sumida, Arihiro; Opthof, Tobias; Ishiguro, Yuko S; Kadomatsu, Kenji; Murohara, Toyoaki; Kodama, Itsuo

    2011-01-01

    Several growth factors are effective for salvaging myocardium and limiting infarct size in experimental studies with small animals. Their benefit in large animals and feasibility in clinical practice remains to be elucidated. We investigated the cardioprotective effect of midkine (MK) in swine subjected to ischemia/reperfusion (I/R). I/R was created by left anterior descending coronary artery occlusion for 45 min using a percutaneous over-the-wire balloon catheter. MK protein was injected as a bolus through the catheter at the initiation of reperfusion [MK-treated (MKT) group]. Saline was injected in controls (CONT). Infarct size/area at risk (24 h after I/R) in MKT was almost five times smaller than in CONT. Echocardiography in MKT revealed a significantly higher percent wall thickening of the interventricular septum, a higher left ventricular (LV) fractional shortening, and a lower E/e(') (ratio of transmitral to annular flow) compared with CONT. LV catheterization in MKT showed a lower LV end-diastolic pressure, and a higher dP/dt(max) compared with CONT. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling-positive myocytes and CD45-positive cell infiltration in the peri-infarct area were significantly less in MKT than in CONT. Here, we demonstrate that a single intracoronary injection of MK protein in swine hearts at the onset of reperfusion dramatically reduces infarct size and ameliorates systolic/diastolic LV function. This beneficial effect is associated with a reduction of apoptotic and inflammatory reactions. MK application during percutaneous coronary intervention may become a promising adjunctive therapy in acute coronary syndromes.

  3. Preventive administration of cromakalim reduces aquaporin-4 expression and blood-brain barrier permeability in a rat model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Shilei Wang; Yanting Wang; Yan Jiang; Qingxian Chang; Peng Wang; Shiduan Wang

    2011-01-01

    Cromakalim, an adenosine triphosphate-sensitive potassium channel opener, exhibits protective effects on cerebral ischemia/reperfusion injury. However, there is controversy as to whether this effect is associated with aquaporin-4 and blood-brain barrier permeability. Immunohistochemistry results show that preventive administration of cromakalim decreased aquaporin-4 and IgG protein expression in rats with ischemia/reperfusion injury; it also reduced blood-brain barrier permeability, and alleviated brain edema, ultimately providing neuroprotection.

  4. Characterization of microparticles after hepatic ischemia-reperfusion injury.

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    Christopher M Freeman

    Full Text Available BACKGROUND: Hepatic ischemia-reperfusion (I/R is a well-studied model of liver injury and has demonstrated a biphasic injury followed by recovery and regeneration. Microparticles (MPs are a developing field of study and these small membrane bound vesicles have been shown to have effector function in other physiologic and pathologic states. This study was designed to quantify the levels of MPs from various cell origins-platelets, neutrophils, and endolethial cells-following hepatic ischemia-reperfusion injury. METHODS: A murine model was used with mice undergoing 90 minutes of partial hepatic ischemia followed by various times of reperfusion. Following reperfusion, plasma samples were taken and MPs of various cell origins were labeled and levels were measured using flow cytometry. Additionally, cell specific MPs were further assessed by Annexin V, which stains for the presence of phosphatidylserine, a cell surface marker linked to apoptosis. Statistical analysis was performed using one-way analysis of variance with subsequent Student-Newman-Keuls test with data presented as the mean and standard error of the mean. RESULTS: MPs from varying sources show an increase in circulating levels following hepatic I/R injury. However, the timing of the appearance of different MP subtypes differs for each cell type. Platelet and neutrophil-derived MP levels demonstrated an acute elevation following injury whereas endothelial-derived MP levels demonstrated a delayed elevation. CONCLUSION: This is the first study to characterize circulating levels of cell-specific MPs after hepatic I/R injury and suggests that MPs derived from platelets and neutrophils serve as markers of inflammatory injury and may be active participants in this process. In contrast, MPs derived from endothelial cells increase after the injury response during the reparative phase and may be important in angiogenesis that occurs in the regenerating liver.

  5. Effects of low molecular weight heparin-superoxide dismutase conjugate on serum levels of nitric oxide, glutathione peroxidase, and myeloperoxidase in a gerbil model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Qingde Wang; Guixiang Cui; Hongxia Liu; Yizhao Li; Fengshan Wang

    2008-01-01

    BACKGROUND: Several studies have demonstrated that low molecular weight heparin-superoxide dismutase (LMWH-SOD) conjugate may exhibit good neuroprotective effects on cerebral ischemia/reperfusion injury though anticoagulation, decreasing blood viscosity, having anti-inflammatory activity, and scavenging oxygen free radicals. OBJECTIVE: To investigate the intervention effects of LMWH-SOD conjugate on serum levels of nitric oxide (NO), glutathione peroxidase (GSH-Px), and myeloperoxidase (MPO) following cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING: A randomized, controlled, and neurobiochemical experiment was performed at the Institute of Biochemical Pharmacy, School of Pharmaceutical Sciences, Shandong University between April and July 2004. MATERIALS: A total of 60 Mongolian gerbils of either gender were included in this study. Total cerebral ischemia/reperfusion injury was induced in 50 gerbils by occluding bilateral common carotid arteries. The remaining 10 gerbils received a sham-operation (sham-operated group). Kits of SOD, NO, and MPO were sourced from Nanjing Jiancheng Bioengineering Institute, China. LMWH, SOD, and LMWH-SOD conjugates were provided by Institute of Biochemistry and Biotechnique, Shandong University, China. METHODS: Fifty successful gerbil models of total cerebral ischemia/reperfusion injury were evenly randomized to five groups: physiological saline, LMWH-SOD, SOD, LMWH + SOD, and LMWH. At 2 minutes prior to ischemia, 0.5 mL/65 g physiological saline, 20 000 U/kg LMWH-SOD conjugate, 20 000 U/kg SOD, a mixture of SOD (20 000 U/kg) and LMWH (LMWH dose calculated according to weight ratio, LMWH: SOD = 23.6:51), and LMWH (dose as in the LMWH + SOD group) were administered through the femoral artery in each above-mentioned group, respectively. MAIN OUTCOME MEASURES: Serum levels of NO, MPO, and GSH-Px. RESULTS: Compared with 10 sham-operated gerbils, the cerebral ischemia/reperfusion injury gerbils exhibited decreased serum

  6. Effect of minocycline on cerebral ischemia- reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Yuanyin Zheng; Lijuan Xu; Jinbao Yin; Zhichao Zhong; Hongling Fan; Xi Li; Quanzhong Chang

    2013-01-01

    Minocylcine, a tetracycline derivate, has been shown to cross the blood-brain barrier and enter the central nervous system. In this study, cerebral ischemia-reperfusion injury models were established using the suture method, and minocycline was immediately injected intraperitoneally after cerebral ischemia-reperfusion (22.5 mg/kg, initially 45 mg/kg) at a 12-hour interval. Results showed that after minocycline treatment, the volume of cerebral infarction was significantly reduced, the number of surviving cell in the hippocampal CA1 region increased, the number of apoptotic cells decreased, the expression of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 protein was down-regulated, and the escape latency in the water maze test was significantly shortened compared with the ischemia-reperfusion group. Our experimental findings indicate that minocycline can protect against neuronal injury induced by focal ischemia-reperfusion, which may be mediated by the inhibition of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 protein expression.

  7. Effects of the mitochondrial calcium uniporter on cerebral edema in a rat model of cerebral ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Linlin Li; Shilei Wang; Haihong Luan

    2011-01-01

    The present study investigated the effects of the mitochondrial calcium uniporter inhibitor ruthenium red and the agonist spermine on cerebral edema in rats with cerebral ischemia reperfusion injury.Left middle cerebral artery occlusion (MCAO) was induced in rats using the suture method.Following 24 hours of ischemic reperfusion, neurological function scores of rats with MCAO, and rats pretreated with ruthenium red and spermine were significantly lower, however, water content of brain tissue, aquaporin 4 expression and immunoglobulin G (IgG) exudation were significantly higher than those of sham-operated rats.Compared with MCAO rats and spermine-treated rats, neurological function scores were considerably higher, and brain tissue water content, aquaporin 4 expression and IgG exudation decreased in ruthenium red-treated rats.These findings suggest that preventive application of the mitochondrial calcium uniporter inhibitor ruthenium red can significantly decrease aquaporin 4 and IgG expression, influence the permeability of the blood brain barrier, and thereby decrease the extent of cerebral edema.

  8. Melatonin combined with exercise cannot alleviate cerebral injury in a rat model of focal cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Seunghoon Lee; Kyu-Tae Chang; Yonggeun Hong; Jinhee Shin; Minkyung Lee; Yunkyung Hong; Sang-Kil Lee; Youngjeon Lee; Tserentogtokh Lkhagvasuren; Dong-Wook Kim; Young-Ae Yang

    2012-01-01

    Previous studies have demonstrated that melatonin combined with exercise can alleviate secondary damage after spinal cord injury in rats. Therefore, it is hypothesized that melatonin combined with exercise can also alleviate ischemic brain damage. In this study, adult rats were subjected to right middle cerebral artery occlusion after receiving 10 mg/kg melatonin or vehicle subcutaneously twice daily for 14 days. Forced exercise using an animal treadmill was performed at 20 m/min for 30 minutes per day for 6 days prior to middle cerebral artery occlusion. After middle cerebral artery occlusion, each rat received melatonin combined with exercise, melatonin or exercise alone equally for 7 days until sacrifice. Interestingly, rats receiving melatonin combined with exercise exhibited more severe neurological deficits than those receiving melatonin or exercise alone. Hypoxia-inducible factor 1α mRNA in the brain tissue was upregulated in rats receiving melatonin combined with exercise. Similarly, microtubule associated protein-2 mRNA expression was significantly upregulated in rats receiving melatonin alone. Chondroitin sulfate proteoglycan 4 (NG2) mRNA expression was significantly decreased in rats receiving melatonin combined with exercise as well as in rats receiving exercise alone. Furthermore, neural cell loss in the primary motor cortex was significantly reduced in rats receiving melatonin or exercise alone, but the change was not observed in rats receiving melatonin combined with exercise. These findings suggest that excessive intervention with melatonin, exercise or their combination may lead to negative effects on ischemia/reperfusion-induced brain damage.

  9. Study on Effect of Shenmai Injection Protecting Myocardium against Ischemia-Reperfusion Injury in Thrombolytic Therapy with Urokinase for Acute Myocardial Infarction Patient Evaluated by 99mTc-MIBI Myocardial Imaging

    Institute of Scientific and Technical Information of China (English)

    郭松鹏; 张言镇

    2001-01-01

    Objective: To evaluate the myocardial protecting effect of Shenmai injection (SMI) against ischemia/reperfusion injury in thrombolytic therapy with urokinase (UK) for acute myocardial infarction patients by 99mTc-MIBI myocardial imaging (SPECT). Methods: Five hundred and thirty-seven patients were divided into two groups randomly. The SMI group (n=292) was treated with thrombolytictreatment plus SMI and the control group (n=245) with thrombolytic treatment solely. Single photon emission computed tomography (SPECT) was carried out on the 7th day after thrombolysis to determine the ischemic myocardial area (IMA) and ejection fraction (EF) in both groups and compared. Results: The infarction related area (IRA) of reperfusion rate in the two groups was not different significantly (72.26% vs 72.65%, P >0.05). The IMA in patients of the SMI group, no matter with or without reperfused IRA (211 cases and 81 cases) respectively, was significantly lower than that in the control group (178 cases and 67 cases) respectively, P<0.01 and P<0.05 respectively. The EF value in the SMI group was significantly higher than that in the control group (P<0.01). Conclusion:Using SMI in early stage of thrombolytic treatment in acute myocardial infarction could significantly reduce IMA and increase EF. SMI showed good protective effect against myocardial ischemia/reperfusion injury in thrombolytic treatment.

  10. Study on Effect of Shenmai Injection Protecting Myocardium against Ischemia-Reperfusion Injury in Thrombolytic Therapy with Urokinase for Acute Myocardial Infarction Patient Evaluated by 99mTc-MIBI Myocardial Imaging

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To evaluate the myocardial protecting effect of Shenmai injection (SMI) against ischemia/reperfusion injury in thrombolytic therapy with urokinase (UK) for acute myocardial infarction patients by 99mTc-MIBI myocardial imaging (SPECT). Methods: Five hundred and thirty-seven patients were divided into two groups randomly. The SMI group (n=292) was treated with thrombolytictreatment plus SMI and the control group (n=245) with thrombolytic treatment solely. Single photon emission computed tomography (SPECT) was carried out on the 7th day after thrombolysis to determine the ischemic myocardial area (IMA) and ejection fraction (EF) in both groups and compared. Results: The infarction related area (IRA) of reperfusion rate in the two groups was not different significantly (72.26% vs 72.65%, P >0.05). The IMA in patients of the SMI group, no matter with or without reperfused IRA (211 cases and 81 cases) respectively, was significantly lower than that in the control group (178 cases and 67 cases) respectively, P<0.01 and P<0.05 respectively. The EF value in the SMI group was significantly higher than that in the control group (P<0.01). Conclusion:Using SMI in early stage of thrombolytic treatment in acute myocardial infarction could significantly reduce IMA and increase EF. SMI showed good protective effect against myocardial ischemia/reperfusion injury in thrombolytic treatment.

  11. Effects of valproic acid and dexamethasone administration on early bio-markers and gene expression profile in acute kidney ischemia-reperfusion injury in the rat.

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    Ryan W Speir

    Full Text Available Renal ischemia-reperfusion (IR causes acute kidney injury (AKI with high mortality and morbidity. The objective of this investigation was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Under general anesthesia, left renal ischemia was induced in Wister rats by occluding renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n = 8/group received Valproic Acid (150 mg/kg; VPA, Dexamethasone (3 mg/kg; Dex or Vehicle (saline intraperitoneally. Animals were sacrificed at 3, 24 or 120 h post-IR. Plasma creatinine (mg/dL at 24 h was reduced (P<0.05 in VPA (2.7±1.8 and Dex (2.3±1.2 compared to Vehicle (3.8±0.5 group. At 3 h, urine albumin (mg/mL was higher in Vehicle (1.47±0.10, VPA (0.84±0.62 and Dex (1.04±0.73 compared to naïve (uninjured/untreated control (0.14±0.26 group. At 24 h post-IR urine lipocalin-2 (μg/mL was higher (P<0.05 in VPA, Dex and Vehicle groups (9.61-11.36 compared to naïve group (0.67±0.29; also, kidney injury molecule-1 (KIM-1; ng/mL was higher (P<0.05 in VPA, Dex and Vehicle groups (13.7-18.7 compared to naïve group (1.7±1.9. Histopathology demonstrated reduced (P<0.05 ischemic injury in the renal cortex in VPA (Grade 1.6±1.5 compared to Vehicle (Grade 2.9±1.1. Inflammatory cytokines IL1β and IL6 were downregulated and anti-apoptotic molecule BCL2 was upregulated in VPA group. Furthermore, kidney DNA microarray demonstrated reduced injury, stress, and apoptosis related gene expression in the VPA administered rats. VPA appears to ameliorate kidney IR injury via reduced inflammatory cytokine, apoptosis/stress related gene expression, and improved regeneration. KIM-1, lipocalin-2 and albumin appear to be promising early urine biomarkers for the diagnosis of AKI.

  12. Effects of Valproic Acid and Dexamethasone Administration on Early Bio-Markers and Gene Expression Profile in Acute Kidney Ischemia-Reperfusion Injury in the Rat

    Science.gov (United States)

    Speir, Ryan W.; Stallings, Jonathan D.; Andrews, Jared M.; Gelnett, Mary S.; Brand, Timothy C.; Salgar, Shashikumar K.

    2015-01-01

    Renal ischemia-reperfusion (IR) causes acute kidney injury (AKI) with high mortality and morbidity. The objective of this investigation was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Under general anesthesia, left renal ischemia was induced in Wister rats by occluding renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n = 8/group) received Valproic Acid (150 mg/kg; VPA), Dexamethasone (3 mg/kg; Dex) or Vehicle (saline) intraperitoneally. Animals were sacrificed at 3, 24 or 120 h post-IR. Plasma creatinine (mg/dL) at 24 h was reduced (P<0.05) in VPA (2.7±1.8) and Dex (2.3±1.2) compared to Vehicle (3.8±0.5) group. At 3 h, urine albumin (mg/mL) was higher in Vehicle (1.47±0.10), VPA (0.84±0.62) and Dex (1.04±0.73) compared to naïve (uninjured/untreated control) (0.14±0.26) group. At 24 h post-IR urine lipocalin-2 (μg/mL) was higher (P<0.05) in VPA, Dex and Vehicle groups (9.61–11.36) compared to naïve group (0.67±0.29); also, kidney injury molecule-1 (KIM-1; ng/mL) was higher (P<0.05) in VPA, Dex and Vehicle groups (13.7–18.7) compared to naïve group (1.7±1.9). Histopathology demonstrated reduced (P<0.05) ischemic injury in the renal cortex in VPA (Grade 1.6±1.5) compared to Vehicle (Grade 2.9±1.1). Inflammatory cytokines IL1β and IL6 were downregulated and anti-apoptotic molecule BCL2 was upregulated in VPA group. Furthermore, kidney DNA microarray demonstrated reduced injury, stress, and apoptosis related gene expression in the VPA administered rats. VPA appears to ameliorate kidney IR injury via reduced inflammatory cytokine, apoptosis/stress related gene expression, and improved regeneration. KIM-1, lipocalin-2 and albumin appear to be promising early urine biomarkers for the diagnosis of AKI. PMID:25970334

  13. Erythropoietin reduces apoptosis of brain tissue cells in rats after cerebral ischemia/reperfusion injury: a characteristic analysis using magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Chun-juan Jiang

    2016-01-01

    Full Text Available Some in vitro experiments have shown that erythropoietin (EPO increases resistance to apoptosis and facilitates neuronal survival following cerebral ischemia. However, results from in vivo studies are rarely reported. Perfusion-weighted imaging (PWI and diffusion-weighted imaging (DWI have been applied successfully to distinguish acute cerebral ischemic necrosis and penumbra in living animals; therefore, we hypothesized that PWI and DWI could be used to provide imaging evidence in vivo for the conclusion that EPO could reduce apoptosis in brain areas injured by cerebral ischemia/reperfusion. To validate this hypothesis, we established a rat model of focal cerebral ischemia/reperfusion injury, and treated with intra-cerebroventricular injection of EPO (5,000 U/kg 20 minutes before injury. Brain tissue in the ischemic injury zone was sampled using MRI-guided localization. The relative area of abnormal tissue, changes in PWI and DWI in the ischemic injury zone, and the number of apoptotic cells based on TdT-mediated dUTP-biotin nick end-labeling (TUNEL were assessed. Our findings demonstrate that EPO reduces the relative area of abnormally high signal in PWI and DWI, increases cerebral blood volume, and decreases the number of apoptotic cells positive for TUNEL in the area injured by cerebral ischemia/reperfusion. The experiment provides imaging evidence in vivo for EPO treating cerebral ischemia/reperfusion injury.

  14. Erythropoietin reduces apoptosis of brain tissue cells in rats after cerebral ischemia/reperfusion injury:a characteristic analysis using magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    Chun-juan Jiang; Zhong-juan Wang; Yan-jun Zhao; Zhui-yang Zhang; Jing-jing Tao; Jian-yong Ma

    2016-01-01

    Somein vitro experiments have shown that erythropoietin (EPO) increases resistance to apoptosis and facilitates neuronal survival follow-ing cerebral ischemia. However, results fromin vivo studies are rarely reported. Perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) have been applied successfully to distinguish acute cerebral ischemic necrosis and penumbra in living animals; therefore, we hypothesized that PWI and DWI could be used to provide imaging evidencein vivo for the conclusion that EPO could reduce apoptosis in brain areas injured by cerebral ischemia/reperfusion. To validate this hypothesis, we established a rat model of focal cerebral ischemia/reperfusion injury, and treated with intra-cerebroventricular injection of EPO (5,000 U/kg) 20 minutes before injury. Brain tissue in the ischemic injury zone was sampled using MRI-guided localization. The relative area of abnormal tissue, changes in PWI and DWI in the ischemic injury zone, and the number of apoptotic cells based on TdT-mediated dUTP-biotin nick end-labeling (TUNEL) were assessed. Our ifndings demonstrate that EPO reduces the relative area of abnormally high signal in PWI and DWI, increases cerebral blood volume, and decreases the number of apoptotic cells positive for TUNEL in the area injured by cerebral ischemia/reperfusion. The experiment pro-vides imaging evidencein vivo for EPO treating cerebral ischemia/reperfusion injury.

  15. Erythropoietin reduces apoptosis of brain tissue cells in rats after cerebral ischemia/reperfusion injury: a characteristic analysis using magnetic resonance imaging.

    Science.gov (United States)

    Jiang, Chun-Juan; Wang, Zhong-Juan; Zhao, Yan-Jun; Zhang, Zhui-Yang; Tao, Jing-Jing; Ma, Jian-Yong

    2016-09-01

    Some in vitro experiments have shown that erythropoietin (EPO) increases resistance to apoptosis and facilitates neuronal survival following cerebral ischemia. However, results from in vivo studies are rarely reported. Perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) have been applied successfully to distinguish acute cerebral ischemic necrosis and penumbra in living animals; therefore, we hypothesized that PWI and DWI could be used to provide imaging evidence in vivo for the conclusion that EPO could reduce apoptosis in brain areas injured by cerebral ischemia/reperfusion. To validate this hypothesis, we established a rat model of focal cerebral ischemia/reperfusion injury, and treated with intra-cerebroventricular injection of EPO (5,000 U/kg) 20 minutes before injury. Brain tissue in the ischemic injury zone was sampled using MRI-guided localization. The relative area of abnormal tissue, changes in PWI and DWI in the ischemic injury zone, and the number of apoptotic cells based on TdT-mediated dUTP-biotin nick end-labeling (TUNEL) were assessed. Our findings demonstrate that EPO reduces the relative area of abnormally high signal in PWI and DWI, increases cerebral blood volume, and decreases the number of apoptotic cells positive for TUNEL in the area injured by cerebral ischemia/reperfusion. The experiment provides imaging evidence in vivo for EPO treating cerebral ischemia/reperfusion injury.

  16. Activation of ALDH2 with Low Concentration of Ethanol Attenuates Myocardial Ischemia/Reperfusion Injury in Diabetes Rat Model

    Directory of Open Access Journals (Sweden)

    Pin-Fang Kang

    2016-01-01

    Full Text Available The aim of this paper is to observe the change of mitochondrial aldehyde dehydrogenase 2 (ALDH2 when diabetes mellitus (DM rat heart was subjected to ischemia/reperfusion (I/R intervention and analyze its underlying mechanisms. DM rat hearts were subjected to 30 min regional ischemia and 120 min reperfusion in vitro and pretreated with ALDH2 activator ethanol (EtOH; cardiomyocyte in high glucose (HG condition was pretreated with ALDH2 activator Alda-1. In control I/R group, myocardial tissue structure collapse appeared. Compared with control I/R group, left ventricular parameters, SOD activity, the level of Bcl-2/Bax mRNA, ALDH2 mRNA, and protein expressions were decreased and LDH and MDA contents were increased, meanwhile the aggravation of myocardial structure injury in DM I/R group. When DM I/R rats were pretreated with EtOH, left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 expression were increased; LDH, MDA, and myocardial structure injury were attenuated. Compared with DM + EtOH I/R group, cyanamide (ALDH2 nonspecific blocker, atractyloside (mitoPTP opener, and wortmannin (PI3K inhibitor groups all decreased left ventricular parameters, SOD, Bcl-2/Bax, and ALDH2 and increased LDH, MDA, and myocardial injury. When cardiomyocyte was under HG condition, CCK-8 activity and ALDH2 protein expression were decreased. Alda-1 increased CCK-8 and ALDH2. Our findings suggested enhanced ALDH2 expression in diabetic I/R rats played the cardioprotective role, maybe through activating PI3K and inhibiting mitoPTP opening.

  17. Bilateral ovarian ischemia/reperfusion injury and treatment options in rats with an induced model of diabetes

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    Omer Erkan Yapca

    2014-04-01

    Full Text Available Objective(s:This study investigated the effects of melatonin, famotidine, mirtazapine, and thiamine pyrophosphate on ischemia/reperfusion (I/R injury in diabetic rats and evaluated oxidant and antioxidant marker measurement results. It also examined the effects of the drugs aimed at preventing infertility that may result from I/R injury. Materials and Methods: Diabetic rats were divided into a control group (IRC to be exposed to I/R, an ovarian I/R + 2.2 mg/kg melatonin (IRML group, an ovarian I/R + famotidine (IRFA group, an ovarian I/R + 20 mg/kg mirtazapine (IRMR group, an ovarian I/R + 20 mg/kg thiamine pyrophosphate (IRTP group, and a sham operation (SO group. Results: In the control group exposed to I/R, the levels of the oxidant parameters Malondialdehyde (MDA and Myeloperoxidase(MPO were significantly higher compared with the SO group, while the levels of the antioxidant parameters glutathione (GSH, Glutathioneperoxidase(GPO, Glutathione reductase (GSHRd, Glutathione S - transferase (GST, and[y1]   Superoxide dismutase (SOD were significantly lower. Melatonin, famotidine, mirtazapine, and thiamin pyrophosphate prevented a rise in oxidant parameters and a decrease in antioxidants in ovarian tissue exposed to I/R. However, apart from thiamin pyrophosphate, none of the drugs were able to prevent infertility caused by I/R injury.   Conclusion: Prevention of ovarian I/R injury-related infertility in rats with induced diabetes is not through antioxidant activity. Thiamine pyrophosphate prevents infertility through an as yet unknown mechanism. This study suggests that thiamine pyrophosphate may be useful in the prevention of I/R-related infertility in diabetics.

  18. Rosiglitazone Affects Nitric Oxide Synthases and Improves Renal Outcome in a Rat Model of Severe Ischemia/Reperfusion Injury

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    Boris Betz

    2012-01-01

    Full Text Available Background. Nitric oxide (NO-signal transduction plays an important role in renal ischemia/reperfusion (I/R injury. NO produced by endothelial NO-synthase (eNOS has protective functions whereas NO from inducible NO-synthase (iNOS induces impairment. Rosiglitazone (RGZ, a peroxisome proliferator-activated receptor (PPAR-γ agonist exerted beneficial effects after renal I/R injury, so we investigated whether this might be causally linked with NOS imbalance. Methods. RGZ (5 mg/kg was administered i.p. to SD-rats (f subjected to bilateral renal ischemia (60 min. Following 24 h of reperfusion, inulin- and PAH-clearance as well as PAH-net secretion were determined. Morphological alterations were graded by histopathological scoring. Plasma NOx-production was measured. eNOS and iNOS expression was analyzed by qPCR. Cleaved caspase 3 (CC3 was determined as an apoptosis indicator and ED1 as a marker of macrophage infiltration in renal tissue. Results. RGZ improves renal function after renal I/R injury (PAH-/inulin-clearance, PAH-net secretion and reduces histomorphological injury. Additionally, RGZ reduces NOx plasma levels, ED-1 positive cell infiltration and CC3 expression. iNOS-mRNA is reduced whereas eNOS-mRNA is increased by RGZ. Conclusion. RGZ has protective properties after severe renal I/R injury. Alterations of the NO pathway regarding eNOS and iNOS could be an explanation of the underlying mechanism of RGZ protection in renal I/R injury.

  19. Prednisolone as preservation additive prevents from ischemia reperfusion injury in a rat model of orthotopic lung transplantation.

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    Patrick Paulus

    Full Text Available The lung is, more than other solid organs, susceptible for ischemia reperfusion injury after orthotopic transplantation. Corticosteroids are known to potently suppress pro-inflammatory processes when given in the post-operative setting or during rejection episodes. Whereas their use has been approved for these clinical indications, there is no study investigating its potential as a preservation additive in preventing vascular damage already in the phase of ischemia. To investigate these effects we performed orthotopic lung transplantations (LTX in the rat. Prednisolone was either added to the perfusion solution for lung preservation or omitted and rats were followed for 48 hours after LTX. Prednisolone preconditioning significantly increased survival and diminished reperfusion edema. Hypoxia induced vasoactive cytokines such as VEGF were reduced. Markers of leukocyte invasiveness like matrix metalloprotease (MMP-2, or common pro-inflammatory molecules like the CXCR4 receptor or the chemokine (C-C motif ligand (CCL-2 were downregulated by prednisolone. Neutrophil recruitment to the grafts was only increased in Perfadex treated lungs. Together with this, prednisolone treated animals displayed significantly reduced lung protein levels of neutrophil chemoattractants like CINC-1, CINC-2α/β and LIX and upregulated tissue inhibitor of matrix metalloproteinase (TIMP-1. Interestingly, lung macrophage invasion was increased in both, Perfadex and prednisolone treated grafts, as measured by MMP-12 or RM4. Markers of anti-inflammatory macrophage transdifferentiation like MRC-1, IL-13, IL-4 and CD163, significantly correlated with prednisolone treatment. These observations lead to the conclusion that prednisolone as an additive to the perfusion solution protects from hypoxia triggered danger signals already in the phase of ischemia and thus reduces graft edema in the phase of reperfusion. Additionally, prednisolone preconditioning might also lead to

  20. Does machine perfusion decrease ischemia reperfusion injury?

    Science.gov (United States)

    Bon, D; Delpech, P-O; Chatauret, N; Hauet, T; Badet, L; Barrou, B

    2014-06-01

    In 1990's, use of machine perfusion for organ preservation has been abandoned because of improvement of preservation solutions, efficient without perfusion, easy to use and cheaper. Since the last 15 years, a renewed interest for machine perfusion emerged based on studies performed on preclinical model and seems to make consensus in case of expanded criteria donors or deceased after cardiac death donations. We present relevant studies highlighted the efficiency of preservation with hypothermic machine perfusion compared to static cold storage. Machines for organ preservation being in constant evolution, we also summarized recent developments included direct oxygenation of the perfusat. Machine perfusion technology also enables organ reconditioning during the last hours of preservation through a short period of perfusion on hypothermia, subnormothermia or normothermia. We present significant or low advantages for machine perfusion against ischemia reperfusion injuries regarding at least one primary parameter: risk of DFG, organ function or graft survival.

  1. Ketamine inhibits c-Jun protein expression in mouse hippocampus following cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Feng Xiao; Liangzhi Xiong; Qingxiu Wang; Long Zhou; Qingshan Zhou

    2012-01-01

    A model of cerebral ischemia and reperfusion was established in mice. Mice were treated with ketamine via intraperitoneal injection immediately following ischemia or ischemia/reperfusion. Ketamine did not remarkably change infarct volume in mice immediately following ischemia, but injection immediately following ischemia/reperfusion significantly decreased infarct volume. Ketamine injection immediately after ischemia or ischemia/reperfusion inhibited c-Jun protein expression in mouse hippocampus, but nuclear factor kappa B expression was unaltered. In addition, the Longa scale score for neural impairment was not reduced in mice following cerebral ischemia/reperfusion. These results indicate that ketamine can protect mice against cerebral ischemia and reperfusion injury by modulating c-Jun protein expression in mouse hippocampus.

  2. A new gastric ulcer model induced by ischemia-reperfusion in the rat: role of leukocytes on ulceration in rat stomach.

    Science.gov (United States)

    Wada, K; Kamisaki, Y; Kitano, M; Kishimoto, Y; Nakamoto, K; Itoh, T

    1996-01-01

    A new model of gastric ulcer involving damage to the muscularis mucosae was developed by clamping the celiac artery in rat to induce ischemia-reperfusion (I-R) injury. Although erosions with falling off of the gastric mucosa were observed immediately, 24 and 36 hours after the I-R, gastric ulcers involving the injury of muscularis mucosae were observed in the area of gastric glands at 48 and 72 hours after initiation of injury. Administration of omeprazol, a proton pump inhibitor, or pentoxifylline, an anti-leukocyte drug, just after the initiation of injury significantly decreased the total area of ulcers at 72 hours. A combination of omeprazol and pentoxifylline was more effective than either drug alone. An anti-leukocyte adhesion molecule (anti-CD18 antibody) also showed significant inhibitory effect on the development of ulcers at 72 hours and the infiltration of leukocytes into both submucosa and mucosa. These results indicate that in our model, gastric acid together with leukocytes contribute to the development of ulcers following erosions. This model may be used to investigate the mechanisms of the development of gastric ulcer and evaluate antiulcer drugs in a preclinical setting.

  3. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System

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    Guoxing Wang

    2015-11-01

    Full Text Available Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg group. Thirty min after drug infusion, ventricular fibrillation (8 min and cardiopulmonary resuscitation (up to 30 min was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II and Ang (1–7 levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE, ACE2, Ang II type 1 receptor (AT1R, and the Ang (1–7 receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafilfurther boosted the upregulation of endothelial nitric oxide synthase (eNOS, cyclic guanosine monophosphate (cGMP and inducible nitric oxide synthase(iNOS. Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

  4. Sildenafil Protects against Myocardial Ischemia-Reperfusion Injury Following Cardiac Arrest in a Porcine Model: Possible Role of the Renin-Angiotensin System.

    Science.gov (United States)

    Wang, Guoxing; Zhang, Qian; Yuan, Wei; Wu, Junyuan; Li, Chunsheng

    2015-11-12

    Sildenafil, a phosphodiesterase-5 inhibitor sold as Viagra, is a cardioprotector against myocardial ischemia/reperfusion (I/R) injury. Our study explored whether sildenafil protects against I/R-induced damage in a porcine cardiac arrest and resuscitation (CAR) model via modulating the renin-angiotensin system. Male pigs were randomly divided to three groups: Sham group, Saline group, and sildenafil (0.5 mg/kg) group. Thirty min after drug infusion, ventricular fibrillation (8 min) and cardiopulmonary resuscitation (up to 30 min) was conducted in these animals. We found that sildenafil ameliorated the reduced cardiac function and improved the 24-h survival rate in this model. Sildenafil partly attenuated the increases of plasma angiotensin II (Ang II) and Ang (1-7) levels after CAR. Sildenafil also decreased apoptosis and Ang II expression in myocardium. The increases of expression of angiotensin-converting-enzyme (ACE), ACE2, Ang II type 1 receptor (AT1R), and the Ang (1-7) receptor Mas in myocardial tissue were enhanced after CAR. Sildenafil suppressed AT1R up-regulation, but had no effect on ACE, ACE2, and Mas expression. Sildenafil further boosted the upregulation of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) and inducible nitric oxide synthase(iNOS). Collectively, our results suggest that cardioprotection of sildenafil in CAR model is accompanied by an inhibition of Ang II-AT1R axis activation.

  5. Glycogen synthase kinase-3β inhibition protects heart from acute ischemia/reperfusion injury%抑制GSK-3β减轻大鼠急性心肌缺血/再灌注损伤的作用

    Institute of Scientific and Technical Information of China (English)

    殷忠; 薛白; 高好考; 王海昌; 杨晔

    2011-01-01

    AIM: To investigate the effects of TDZD-8, a GSK-3β inhibitor, on acute myocardial ischemia/ reperfusion injury and to determine whether the protection is associated with the downregulation of NF-kB and the inhibition of inflammation. METHODS; Sixty healthy male Sprague Dawley rats were randomly divided into ischemia/reperfusion { I/R group) , ischemia/reperfusion + drug group ( I/R + D group) , ischemia/reperfusion + vehicle group (I/R + V group) and sham group. Rats were subjected to 30 min ischemia followed by 3 h reperfusion. Myocardial infarct sizes were detected by TTC staining and myocardial tissue neutrophil infiltration. Changes in inflammatory factors were evaluated using HE staining and ELISA method. Phosphorylation of NF-kB and GSK-3β was measured by Western blotting, RESULTS; TDZD-8 reduced the infarct size and neutrophil infiltration (P <0. 01) and inhibited NF-kB activation (P <0.01) and levels of cardiac-derived TNF-α and IL-6 (P <0.01 ). CONCLUSION; GSK-3β inhibitor, TDZD-8, can protect myocardial ischemia/reperfusion injury and may be related to the inhibition of NF-kB activation and the inhibition of inflammation.%目的:评估糖原合酶激酶-3β( GSK-3β)抑制剂TDZD-8减轻大鼠急性心肌缺血/再灌注损伤(MIRI)的作用,并探讨此作用是否与其下调NF-kB、抑制炎症有关.方法:取健康雄性SD大鼠60只,随机分为缺血/冉灌注(I/R)组、I/R +TDZD组、I/R+载体(Vehicle,V)组及假手术(Sham)组.大鼠局部心肌缺血30 min,再灌注3h.用TTC染色计算心肌梗死面积,HE染色及ELISA法评估心肌组织中中性粒细胞浸润及炎性因子(TNF-α和IL-6)的变化;用Western blot测定心肌组织中NF-kB、GSK-3β磷酸化的水平.结果:TDZD-8能明显降低心肌梗死的面积和心肌组织中性粒细胞浸润、抑制NF-kB激活以及心肌源性TNF-α和IL-6的浓度(P<0.01).结论:GSK-3β抑制剂TDZD-8能够减轻MIRI,其作用可能与其抑制NF-KB的激活及炎症反应有关.

  6. Quercetin protects the retina by reducing apoptosis due to ischemia-reperfusion injury in a rat model

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    Sedat Arikan

    2015-04-01

    Full Text Available Purpose: This study aimed to investigate the effect of quercetin on apoptotic cell death induced by ischemia-reperfusion (I/R injury in the rat retina. Methods: Twenty-four rats were divided into four equal groups: control, ischemic, solvent, and quercetin. I/R injury was achieved by elevating the intraocular pressure above the perfusion pressure. Intraperitoneal injections of 20 mg/kg of quercetin and dimethyl sulfoxide (DMSO were performed in the quercetin and solvent groups, respectively, immediately prior to I/R injury, and the researchers allowed for the retinas to be reperfused. Forty-eight hours after injury, the thicknesses of the retinal ganglion cell layer (RGCL, inner nuclear layer (INL, inner plexiform layer (IPL, outer plexiform layer (OPL, and outer nuclear layer (ONL were measured in all groups. Moreover, the numbers of terminal deoxynucleotidyl transferase dUTP nick-end-labeled [TUNEL (+] cells and caspase-3 (+ cells in both INL and ONL were evaluated in all groups. Results: The administration of quercetin was found to reduce the thinning of all retinal layers. The mean thickness of INL in the quercetin and ischemic groups was 21 ± 5.6 µm and 16 ± 6.4 µm, respectively (P<0.05. Similarly, the mean thickness of ONL in the quercetin and ischemic groups was 50 ± 12.8 µm and 40 ± 8.7 µm, respectively (P<0.05. The antiapoptotic effect of quercetin in terms of reducing the numbers of both TUNEL (+ cells and caspase-3 (+ cells was significant in INL. The mean number of TUNEL (+ cells in INL in the ischemic and quercetin groups was 476.8 ± 45.6/mm2 and 238.72 ± 251/mm2, respectively (P<0.005. The mean number of caspase-3 (+ cells in INL of ischemic and quercetin groups was 633.6 ± 38.7/mm2 and 342.4 ± 36.1/mm2, respectively (P<0.001. Conclusion: The use of quercetin may be beneficial in the treatment of retinal I/R injury because of its antiapoptotic effect on the retinal layers, particularly in INL.

  7. The effect of metformin on the myocardial tolerance to ischemia-reperfusion injury in the rat model of diabetes mellitus type II.

    Science.gov (United States)

    Kravchuk, Ekaterina; Grineva, Elena; Bairamov, Alekber; Galagudza, Michael; Vlasov, Timur

    2011-01-01

    In recent years, evidence has been accumulated that metformin, an antidiabetic drug in the biguanide class, in addition to its well-recognized glucose-lowering effect, can also reduce cardiovascular mortality in the patients with type 2 diabetes mellitus (T2DM). Besides, there are a few experimental studies on the possibility of the direct anti-ischemic effect of the drug in both type 1 diabetes mellitus and T2DM. In our study, myocardial tolerance to ischemia in rats with neonatal streptozotocin T2DM was investigated using the model of global ischemia-reperfusion of the isolated perfused heart. Metformin was administered i.p. at a dose of 200 mg/kg/day for 3 days prior to isolated heart perfusion. The results showed that both the infarct size and postischemic recovery of left ventricular function were not different between controls and metformin-treated animals. At the same time, the infarct size in the T2DM animals was significantly lower than that in the controls (24.4 ± 7.6% versus 45.0 ± 10.4%, resp., P < .01), indicative of the metabolic preconditioning in T2DM. It follows that the protocol of metformin administration used in this study had not elicited cardioprotective effect in animals with T2DM so that the different mechanism(s) may underlie the beneficial effect of metformin on cardiovascular complications in patients with T2DM which, however, would need further investigation.

  8. The Effect of Metformin on the Myocardial Tolerance to Ischemia-Reperfusion Injury in the Rat Model of Diabetes Mellitus Type II

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    Ekaterina Kravchuk

    2011-01-01

    Full Text Available In recent years, evidence has been accumulated that metformin, an antidiabetic drug in the biguanide class, in addition to its well-recognized glucose-lowering effect, can also reduce cardiovascular mortality in the patients with type 2 diabetes mellitus (T2DM. Besides, there are a few experimental studies on the possibility of the direct anti-ischemic effect of the drug in both type 1 diabetes mellitus and T2DM. In our study, myocardial tolerance to ischemia in rats with neonatal streptozotocin T2DM was investigated using the model of global ischemia-reperfusion of the isolated perfused heart. Metformin was administered i.p. at a dose of 200 mg/kg/day for 3 days prior to isolated heart perfusion. The results showed that both the infarct size and postischemic recovery of left ventricular function were not different between controls and metformin-treated animals. At the same time, the infarct size in the T2DM animals was significantly lower than that in the controls (24.4 ± 7.6% versus 45.0 ± 10.4%, resp., P<.01, indicative of the metabolic preconditioning in T2DM. It follows that the protocol of metformin administration used in this study had not elicited cardioprotective effect in animals with T2DM so that the different mechanism(s may underlie the beneficial effect of metformin on cardiovascular complications in patients with T2DM which, however, would need further investigation.

  9. Ginsenoside Rd inhibits apoptosis following spinal cord ischemia/reperfusion injur y

    Institute of Scientific and Technical Information of China (English)

    Baogang Wang; Qingsan Zhu; Xiaxia Man; Li Guo; Liming Hao

    2014-01-01

    Ginsenoside Rd has a clear neuroprotective effect against ischemic stroke. We aimed to verify the neuroprotective effect of ginsenoside Rd in spinal cord ischemia/reperfusion injury and explore its anti-apoptotic mechanisms. We established a spinal cord ischemia/reperfusion injury model in rats through the occlusion of the abdominal aorta below the level of the renal artery for 1 hour. Successfully established models were injected intraperitoneally with 6.25, 12.5, 25 or 50 mg/kg per day ginsenoside Rd. Spinal cord morphology was observed at 1, 3, 5 and 7 days after spinal cord ischemia/reperfusion injury. Intraperitoneal injection of ginsenoside Rd in ischemia/reperfusion injury rats not only improved hindlimb motor function and the morphology of motor neurons in the anterior horn of the spinal cord, but it also reduced neuronal apoptosis. The optimal dose of ginsenoside Rd was 25 mg/kg per day and the optimal time point was 5 days after ischemia/reperfusion. Immunohistochemistry and western blot analysis showed ginsenoside Rd dose-de-pendently inhibited expression of pro-apoptotic Caspase 3 and down-regulated the expression of the apoptotic proteins ASK1 and JNK in the spinal cord of rats with spinal cord ischemia/reper-fusion injury. These ifndings indicate that ginsenoside Rd exerts neuroprotective effects against spinal cord ischemia/reperfusion injury and the underlying mechanisms are achieved through the inhibition of ASK1-JNK pathway and the down-regulation of Caspase 3 expression.

  10. The Effect of Statins and Other Cardiovascular Medication on Ischemia-Reperfusion Damage in a Human DIEP Flap Model: Theoretical and Epidemiological Considerations

    NARCIS (Netherlands)

    van den Heuvel, M.G.; Bast, A.; Ambergen, A.W.; van der Hulst, R.R.

    2012-01-01

    Background. Statins and other cardiovascular medication possess antioxidant capacity. It was examined whether chronic use of these medications protects from the development of ischemia-reperfusion (I/R) related complications after DIEP (Deep Inferior Epigastric Perforator Free Flap) surgery. This pa

  11. Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion Injury

    OpenAIRE

    Yoon-Kyung Chang; Hyunsu Choi; Jin Young Jeong; Ki-Ryang Na; Kang Wook Lee; Beom Jin Lim; Dae Eun Choi

    2016-01-01

    Dapagliflozin, a new type of drug used to treat diabetes mellitus (DM), is a sodium/glucose cotransporter 2 (SGLT2) inhibitor. Although some studies showed that SGLT2 inhibition attenuated reactive oxygen generation in diabetic kidney the role of SGLT2 inhibition is unknown. We evaluated whether SLT2 inhibition has renoprotective effects in ischemia-reperfusion (IR) models. We evaluated whether dapagliflozin reduces renal damage in IR mice model. In addition, hypoxic HK2 cells were treated wi...

  12. The Protective Effect of MicroRNA-320 on Left Ventricular Remodeling after Myocardial Ischemia-Reperfusion Injury in the Rat Model

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    Chun-Li Song

    2014-09-01

    Full Text Available The primary objective of this study investigated the role of microRNA-320 (miR-320 on left ventricular remodeling in the rat model of myocardial ischemia-reperfusion (I/R injury, and we intended to explore the myocardial mechanism of miR-320-mediated myocardium protection. We collected 120 male Wistar rats (240–280 g in this study and then randomly divided them into three groups: (1 sham surgery group (sham group: n = 40; (2 ischemia-reperfusion model group (I/R group: n = 40; and (3 I/R model with antagomir-320 group (I/R + antagomir-320 group: n = 40. Value changes of heart function in transesophageal echocardiography were recorded at various time points (day 1, day 3, day 7, day 15 and day 30 after surgery in each group. Myocardial sections were stained with hematoxylin and eosin (H&E and examined with optical microscope. The degree of myocardial fibrosis was assessed by Sirius Red staining. Terminal dUTP nick end-labeling (TUNEL and qRT-PCR methods were used to measure the apoptosis rate and to determine the miR-320 expression levels in myocardial tissues. Transesophageal echocardiography showed that the values of left ventricular ejection fraction (LVEF, left ventricular fractional shortening (LVFS, left ventricular systolic pressure (LVSP and ±dp/dtmax in the I/R group were obviously lower than those in the sham group, while the left ventricular end-diastolic pressure (LVEDP value was higher than that in the sham group. The values of LVEF, LVFS, LVSP and ±dp/dtmax showed a gradual decrease in the I/R group, while the LVEDP value showed an up tendency along with the extension of reperfusion time. The H&E staining revealed that rat myocardial tissue in the I/R group presented extensive myocardial damage; for the I/R + antagomir-320 group, however, the degree of damage in myocardial cells was obviously better than that of the I/R group. The Sirius Red staining results showed that the degree of myocardial fibrosis in the I/R group was more

  13. Tyrosol attenuates ischemia-reperfusion-induced kidney injury via inhibition of inducible nitric oxide synthase.

    Science.gov (United States)

    Wang, Pengqi; Zhu, Qingjun; Wu, Nan; Siow, Yaw L; Aukema, Harold; O, Karmin

    2013-04-17

    Tyrosol is a natural phenolic antioxidant compound. Oxidative stress represents one of the important mechanisms underlying ischemia-reperfusion-induced kidney injury. The aim of this study was to investigate the effect of tyrosol against ischemia-reperfusion-induced acute kidney injury. The left kidney of Sprague-Dawley rats was subjected to 45 min of ischemia followed by reperfusion for 6 h. Ischemia-reperfusion caused an increase in peroxynitrite formation and lipid peroxidation. The level of nitric oxide (NO) metabolites and the mRNA of inducible nitric oxide synthase (iNOS) were elevated in ischemia-reperfused kidneys. Administration of tyrosol (100 mg/kg body weight) to rats prior to the induction of ischemia significantly reduced peroxynitrite formation, lipid peroxidation, and the level of NO metabolites. Tyrosol administration also attenuated ischemia-reperfusion-induced NF-κB activation and iNOS expression. Such a treatment improved kidney function. Results suggest that tyrosol may have a protective effect against acute kidney injury through inhibition of iNOS-mediated oxidative stress.

  14. Co-administration of the flavanol (−)-epicatechin with doxycycline synergistically reduces infarct size in a model of ischemia reperfusion injury by inhibition of mitochondrial swelling

    Science.gov (United States)

    Ortiz-Vilchis, Pilar; Yamazaki, Katrina Go; Rubio-Gayosso, Ivan; Ramirez-Sanchez, Israel; Calzada, Claudia; Romero-Perez, Diego; Ortiz, Alicia; Meaney, Eduardo; Taub, Pam; Villarreal, Francisco; Ceballos, Guillermo

    2016-01-01

    (−)-Epicatechin (EPI) is cardioprotective in the setting of ischemia/reperfusion (IR) injury and doxycycline (DOX) is known to preserve cardiac structure/function after myocardial infarction (MI). The main objective of this study was to examine the effects of EPI and DOX co-administration on MI size after IR injury and to determine if cardioprotection may involve the mitigation of mitochondrial swelling. For this purpose, a rat model of IR was used. Animals were subjected to a temporary 45 min occlusion of the left anterior descending coronary artery. Treatment consisted of a single or double dose of EPI (10 mg/kg) combined with DOX (5 mg/kg). The first dose was given 15 min prior to reperfusion and the second 12 h post-MI. The effects of EPI +/− DOX on mitochondrial swelling (i.e. mPTP opening) were determined using isolated mitochondria exposed to calcium overload and data examined using isobolographic analysis. To ascertain for the specificity of EPI effects on mitochondrial swelling other flavonoids were also evaluated. Single dose treatment reduced MI size by ~46% at 48 h and 44% at three weeks. Double dosing evidenced a synergistic, 82% reduction at 3 weeks. EPI plus DOX also inhibited mitochondrial swelling in a synergic manner thus, possibly accounting for the cardioprotective effects whereas limited efficacy was observed with the other flavonoids. Given the apparent lack of toxicity in humans, the combination of EPI and DOX may have clinical potential for the treatment of myocardial IR injury. PMID:25281837

  15. KR-31762, a novel KATP channel opener, exerts cardioprotective effects by opening SarcKATP channels in rat models of ischemia/reperfusion-induced heart injury.

    Science.gov (United States)

    Lee, Sung-Hun; Yang, Min-Kyu; Lim, Jong-Hyun; Seo, Ho-Won; Yi, Kyu-Yang; Yoo, Sung-Eun; Lee, Byung-Ho; Won, Hyung-Sik; Lee, Chang-Soo; Choi, Wahn-Soo; Shin, Hwa-Sup

    2008-04-01

    The cardioprotective effects of KR-31762, a newly synthesized K+(ATP) opener, were evaluated in rat models of ischemia/reperfusion (I/R) heart injury. In isolated rat hearts subjected to 30-min global ischemia followed by 30-min reperfusion, KR-31762 (3 and 10 microM) significantly increased the left ventricular developed pressure (LVDP) and double product (heart rate x LVDP) after 30-min reperfusion in a concentration-dependent manner, while decreasing the left ventricular end-diastolic pressure (LVEDP). KR-31762 also significantly increased the time to contracture (TTC) during ischemic period (20.0, 22.4 and 26.4 min for control, 3 and 10 microM, respectively), while decreasing the release of lactate dehydrogenase (LDH) from the heart during 30 min reperfusion (30.4, 14.3 and 19.7 U/g heart weight, respectively). All these parameters except LDH release were reversed by glyburide (1 microM), a nonselective blocker of K+(ATP) channel, but not by 5-hydroxydecanoate, a selective blocker of mitoK+(ATP) channel. In anesthetized rats subjected to 45-min occlusion of left anterior descending coronary artery followed by 90-min reperfusion, KR-31762 significantly decreased the infarct size (60.8, 40.5 and 37.8% for control, 0.3 and 1.0 mg/kg, iv, respectively). KR-31762 slightly relaxed the isolated rat aorta precontracted with methoxamine (IC(50): 23.5 microM). These results suggest that KR-31762 exerts potent cardioprotective effects through the opening of sarcolemmal K(ATP) channel in rat hearts with the minimal vasorelaxant effects.

  16. Does closure of acid-sensing ion channels reduce ischemia/reperfusion injury in the rat brain?

    Institute of Scientific and Technical Information of China (English)

    Jie Wang; Yinghui Xu; Zhigang Lian; Jian Zhang; Tingzhun Zhu; Mengkao Li; Yi Wei; Bin Dong

    2013-01-01

    Acidosis is a common characteristic of brain damage. Because studies have shown that permeable Ca2+-acid-sensing ion channels can mediate the toxic effects of calcium ions, they have become new targets against pain and various intracranial diseases. However, the mechanism associated with expression of these channels remains unclear. This study sought to observe the expression characteristics of permeable Ca2+-acid-sensing ion channels during different reperfusion inflows in rats after cerebral ischemia. The rat models were randomly divided into three groups: adaptive ischemia/reperfusion group, one-time ischemia/reperfusion group, and severe cerebral ischemic injury group. Western blot assays and immunofluorescence staining results exhibited that when compared with the one-time ischemia/reperfusion group, acid-sensing ion channel 3 and Bcl-x/l expression decreased in the adaptive ischemia/reperfusion group. Calmodulin expression was lowest in the adaptive ischemia/reperfusion group. Following adaptive reperfusion, common carotid artery flow was close to normal, and the pH value improved. Results verified that adaptive reperfusion following cerebral ischemia can suppress acid-sensing ion channel 3 expression, significantly reduce Ca2+ influx, inhibit calcium overload, and diminish Ca2+ toxicity. The effects of adaptive ischemia/reperfusion on suppressing cell apoptosis and relieving brain damage were better than that of one-time ischemia/reperfusion.

  17. Autophagy and Liver Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Raffaele Cursio

    2015-01-01

    Full Text Available Liver ischemia-reperfusion (I-R injury occurs during liver resection, liver transplantation, and hemorrhagic shock. The main mode of liver cell death after warm and/or cold liver I-R is necrosis, but other modes of cell death, as apoptosis and autophagy, are also involved. Autophagy is an intracellular self-digesting pathway responsible for removal of long-lived proteins, damaged organelles, and malformed proteins during biosynthesis by lysosomes. Autophagy is found in normal and diseased liver. Although depending on the type of ischemia, warm and/or cold, the dynamic process of liver I-R results mainly in adenosine triphosphate depletion and in production of reactive oxygen species (ROS, leads to both, a local ischemic insult and an acute inflammatory-mediated reperfusion injury, and results finally in cell death. This process can induce liver dysfunction and can increase patient morbidity and mortality after liver surgery and hemorrhagic shock. Whether autophagy protects from or promotes liver injury following warm and/or cold I-R remains to be elucidated. The present review aims to summarize the current knowledge in liver I-R injury focusing on both the beneficial and the detrimental effects of liver autophagy following warm and/or cold liver I-R.

  18. Protective Effects of HDL Against Ischemia/Reperfusion Injury.

    Science.gov (United States)

    Gomaraschi, Monica; Calabresi, Laura; Franceschini, Guido

    2016-01-01

    Several lines of evidence suggest that, besides being a strong independent predictor of the occurrence of primary coronary events, a low plasma high density lipoprotein (HDL) cholesterol level is also associated with short- and long-term unfavorable prognosis in patients, who have recovered from a myocardial infarction, suggesting a direct detrimental effect of low HDL on post-ischemic myocardial function. Experiments performed in ex vivo and in vivo models of myocardial ischemia/reperfusion (I/R) injury have clearly shown that HDL are able to preserve cardiac function when given before ischemia or at reperfusion; the protective effects of HDL against I/R injury have been also confirmed in other tissues and organs, as brain and hind limb. HDL were shown to act on coronary endothelial cells, by limiting the increase of endothelium permeability and promoting vasodilation and neoangiogenesis, on white blood cells, by reducing their infiltration into the ischemic tissue and the release of pro-inflammatory and matrix-degrading molecules, and on cardiomyocytes, by preventing the activation of the apoptotic cascade. Synthetic HDL retains the cardioprotective activity of plasma-derived HDL and may become a useful adjunctive therapy to improve clinical outcomes in patients with acute coronary syndromes or undergoing coronary procedures.

  19. Pharmacological evaluation of glutamate transporter 1 (GLT-1) mediated neuroprotection following cerebral ischemia/reperfusion injury.

    Science.gov (United States)

    Verma, Rajkumar; Mishra, Vikas; Sasmal, Dinakar; Raghubir, Ram

    2010-07-25

    Recently glutamate transporters have emerged as a potential therapeutic target in a wide range of acute and chronic neurological disorders, owing to their novel mode of action. The modulation of GLT-1, a major glutamate transporter has been shown to exert neuroprotection in various models of ischemic injury and motoneuron degeneration. Therefore, an attempt was made to explore its neuroprotective potential in cerebral ischemia/reperfusion injury using ceftriaxone, a GLT-1 modulator. Pre-treatment with ceftriaxone (100mg/kg. i.v) for five days resulted in a significant reduction (Pceftriaxone-mediated increased glutamine synthetase activity by dihydrokainate (DHK), a GLT-1 specific inhibitor, confirms the specific effect of ceftriaxone on GLT-1 activity. In addition, ceftriaxone also induced a significant (P<0.01) increase in [(3)H]-glutamate uptake, mediated by GLT-1 in glial enriched preparation, as evidenced by use of DHK and DL-threo-beta-benzyloxyaspartate (DL-TBOA). Thus, the present study provides overwhelming evidence that modulation of GLT-1 protein expression and activity confers neuroprotection in cerebral ischemia/reperfusion injury.

  20. Amyloid beta-peptide worsens cognitive impairment following cerebral ischemia-reperfusion injury*****

    Institute of Scientific and Technical Information of China (English)

    Bo Song; Qiang Ao; Ying Niu; Qin Shen; Huancong Zuo; Xiufang Zhang; Yandao Gong

    2013-01-01

    Amyloid β-peptide, a major component of senile plaques in Alzheimer’s disease, has been impli-cated in neuronal cel death and cognitive impairment. Recently, studies have shown that the pathogenesis of cerebral ischemia is closely linked with Alzheimer’s disease. In this study, a rat model of global cerebral ischemia-reperfusion injury was established via occlusion of four arteries;meanwhile, fibril ar amyloid β-peptide was injected into the rat lateral ventricle. The Morris water maze test and histological staining revealed that administration of amyloid β-peptide could further aggravate impairments to learning and memory and neuronal cel death in the hippocampus of rats subjected to cerebral ischemia-reperfusion injury. Western blot showed that phosphorylation of tau protein and the activity of glycogen synthase kinase 3β were significantly stronger in cerebral is-chemia-reperfusion injury rats subjected to amyloidβ-peptide administration than those undergoing cerebral ischemia-reperfusion or amyloidβ-peptide administration alone. Conversely, the activity of protein phosphatase 2A was remarkably reduced in rats with cerebral ischemia-reperfusion injury fol owing amyloidβ-peptide administration. These findings suggest that amyloidβ-peptide can po-tentiate tau phosphorylation induced by cerebral ischemia-reperfusion and thereby aggravate cog-nitive impairment.

  1. Stress protein expression in early phase spinal cord ischemia/reperfusion injury*

    Institute of Scientific and Technical Information of China (English)

    Shanyong Zhang; Dankai Wu; Jincheng Wang; Yongming Wang; Guoxiang Wang; Maoguang Yang; Xiaoyu Yang

    2013-01-01

    Spinal cord ischemia/reperfusion injury is a stress injury to the spinal cord. Our previous studies using differential proteomics identified 21 differential y expressed proteins (n > 2) in rabbits with spinal cord ischemia/reperfusion injury. Of these proteins, stress-related proteins included protein disulfide isomerase A3, stress-induced-phosphoprotein 1 and heat shock cognate protein 70. In this study, we established New Zealand rabbit models of spinal cord ischemia/reperfusion injury by abdominal aorta occlusion. Results demonstrated that hind limb function initial y improved after spinal cord ischemia/reperfusion injury, but then deteriorated. The pathological morphology of the spinal cord became aggravated, but lessened 24 hours after reperfusion. However, the numbers of motor neurons and interneurons in the spinal cord gradual y decreased. The expression of protein disulfide isomerase A3, stress-induced-phosphoprotein 1 and heat shock cognate protein 70 was induced by ischemia/reperfusion injury. The expression of these proteins increased within 12 hours after reperfusion, and then decreased, reached a minimum at 24 hours, but subsequently increased again to similar levels seen at 6–12 hours, showing a characterization of induction-inhibition-induc-tion. These three proteins were expressed only in cytoplasm but not in the nuclei. Moreover, the expression was higher in interneurons than in motor neurons, and the survival rate of interneurons was greater than that of motor neurons. It is assumed that the expression of stress-related proteins exhibited a protective effect on neurons.

  2. Research Progress in Animal Model of Lung Ischemia-reperfusion Injury%肺缺血再灌注损伤动物模型的研究进展

    Institute of Scientific and Technical Information of China (English)

    张皓; 齐海

    2014-01-01

    缺血再灌注损伤(IRI)是器官移植研究的重点。肺缺血再灌注损伤(LIRI)的发生与白细胞活化分泌促炎因子、活性氧增多、细胞内钙离子浓度升高等有关,因此研究LIRI主要侧重这几个方面。现在各种动物模型(如鼠、兔、犬等)的建立能够很好地模拟这些发生,解决了临床直接研究的难题。文章就这些方面的研究进展作一综述。%Ischemia-reperfusion injury(IRI)is a focus in the study of organ transplantation.The occurrence of lung ischemia-reperfusion injury(LIRI)and leukocyte activation increased secretion of pro-inflammatory factor,reactive oxygen species,increased intracellular calcium ion concentration and so on,so the research LIRI focused primarily on these aspects.Now all kinds of animal models(such as the rat,rabbit,dog,etc.)the establishment of well simulate these happen,solved the difficult problem of clinical research directly.The article summarizes the progress on these aspects of the research.

  3. Distinct effects of acute pretreatment with lipophilic and hydrophilic statins on myocardial stunning, arrhythmias and lethal injury in the rat heart subjected to ischemia/reperfusion.

    Science.gov (United States)

    Čarnická, S; Adameová, A; Nemčeková, M; Matejíková, J; Pancza, D; Ravingerová, T

    2011-01-01

    Although both lipophilic and more hydrophilic statins share the same pathway of the inhibition of HMG-CoA reductase, their pleiotropic cardioprotective effects associated with the ability to cross cellular membranes, including membranes of heart cells, may differ. To test this hypothesis, isolated rat hearts were Langendorff-perfused either with simvastatin (S, 10 micromol/l) or pravastatin (P, 30 micromol/l), 15 min prior to ischemia. Control untreated hearts (C) were perfused with perfusion medium only. Postischemic contractile dysfunction, reperfusion-induced ventricular arrhythmias and infarct size were investigated after exposure of the hearts to 30-min global ischemia and 2-h reperfusion. Both lipophilic S and hydrophilic P reduced the severity of ventricular arrhythmias (arrhythmia score) from 4.3 +/- 0.2 in C to 3.0 +/- 0 and 2.7 +/- 0.2 in S and P, respectively, (both P statins indicating a different ability to cross cardiac membranes may underlie their distinct cardioprotective effects on myocardial stunning and lethal injury induced by ischemia/reperfusion.

  4. Antioxidative and cardioprotective effects of total flavonoids extracted from Dracocephalum moldavica L. against acute ischemia/reperfusion-induced myocardial injury in isolated rat heart.

    Science.gov (United States)

    Jiang, Jiangtao; Yuan, Xuan; Wang, Ting; Chen, Hongmei; Zhao, Hong; Yan, Xinyan; Wang, Zhiping; Sun, Xiling; Zheng, Qiusheng

    2014-03-01

    This study evaluates antioxidative and cardioprotective effects of total flavonoids extracted from Dracocephalum moldavica L. (DML). The total flavonoids showed remarkable scavenging effects against 1,1-diphenyl-2-picrylhydrazyl, hydroxyl and superoxide anion radicals in vitro. Compared with the ischemia/reperfusion (I/R) group as demonstrated by the use of improved Langendorff retrograde perfusion technology, the total flavonoids (5 μg/mL) pretreatment improved the heart rate and coronary flow, rised left ventricular developed pressure and decreased creatine kinase, lactate dehydrogenase levels in coronary flow. The infarct size/ischemic area at risk of DML-treated hearts was smaller than that of I/R group; the superoxide dismutase activity and glutathione/glutathione disulfide ratio increased and malondialdehyde content reduced obviously (P total flavonoids treatment groups. In conclusion, the total flavonoids possess obvious protective effects on myocardial I/R injury, which may be related to the improvement of myocardial oxidative stress states.

  5. Serum and urinary neutrophil gelatinase-associated lipocalin as a predictor of rat kidney histopathology in an early ischemia-reperfusion model

    Directory of Open Access Journals (Sweden)

    Sahala Panggabean

    2012-11-01

    Full Text Available Background: The severity of ischemia-reperfusion (I/R kidney injury is highly correlated with mortality and morbidity rate. Research on human and animal prove that NGAL predicts kidney injury at early phase. The objective of this study is to prove that the increase in serum and urinary NGAL are correlated with kidney tubular epithelial damage, and this increase has occurred in initiation phase, indicated by rat kidney histopathology in an early I/R model.Methods: Twenty eight male Sprague-Dawley rats were divided into 4 groups: 4 hour sham (Sham 4, 8 hour sham (Sham 8, 10 minute ischemia 4 hour reperfusion (I/R 4 and 10 minute ischemia 8 hour reperfusion (I/R 8. Blood, urine and kidney samples were collected. Serum creatinine level was analyzed with Jaffe method, while serum and urinary NGAL level were analyzed with direct sandwich ELISA method. Evaluation of kidney damage were measured semi quantitatively in tissue stained with HE. Further evaluation to confirm cellular changes on kidney was performed by electron microscope and immunohistochemistry.Results: Serum NGAL was found significantly correlated with degree of kidney tissue damage (ρSpearman NGAL serum = 0.701, p < 0.001, also urinary NGAL (ρSpearman = 0.689, p < 0.001. NGAL expression differs significantly between I/R group and sham (t-test, t = -26635.056, p < 0.001, also kidney damage (t-test, t = -5.028, p < 0.001, and serum and urinary NGAL levels (Mann-Whitney, U = 0, p < 0.001. With cutoff points of 136.95 ng/mL and 58.69 ng/mL subsequently for serum and urinary NGAL , it is found that sensitivity = 1, specificity = 1.Conclusion: Elevation of serum and urinary NGAL are significantly correlated with epithelial tubular kidney damage on rat undergoing early ischaemia reperfusion. (Med J Indones. 2012;21:208-13Keywords: Early I/R kidney injury, kidney histopathology, NGAL

  6. Systemic gene therapy with interleukin-13 attenuates renal ischemia-reperfusion injury

    NARCIS (Netherlands)

    Sandovici, M.; Henning, R. H.; van Goor, H.; Helfrich, W.; de Zeeuw, D.; Deelman, L. E.

    2008-01-01

    Ischemia-reperfusion injury is a leading cause of acute renal failure and a major determinant in the outcome of kidney transplantation. Here we explored systemic gene therapy with a modified adenovirus expressing Interleukin (IL)-13, a cytokine with strong anti-inflammatory and cytoprotective proper

  7. Determinants of tubular bone marrow-derived cell engraftment after renal ischemia/reperfusion in rats

    NARCIS (Netherlands)

    Broekema, M; Harmsen, MC; Koerts, JA; Petersen, AH; van Luyn, MJA; Navis, G; Popa, ER

    2005-01-01

    Background. Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure (ARF). ARF is reversible, due to an innate regenerative process, which is thought to depend partly on bone marrow-derived progenitor cells. The significance of these cells in the repair process has been questioned

  8. Anti-inlfammatory properties of lipoxin A4 protect against diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Jiang-quan Han; Cheng-ling Liu; Zheng-yuan Wang; Ling Liu; Ling Cheng; Ya-dan Fan

    2016-01-01

    Lipoxin A4 can alleviate cerebral ischemia/reperfusion injury by reducing the inlfammatory reaction, but it is currently unclear whether it has a protective effect on diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury. In this study, we established rat models of diabetes mellitus using an intraperitoneal injection of streptozotocin. We then induced focal cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours. After administration of lipoxin A4via the lateral ventricle, infarction volume was reduced, the expression levels of pro-inlfammatory factors tumor necrosis factor alpha and nuclear fac-tor-kappa B in the cerebral cortex were decreased, and neurological functioning was improved. These ifndings suggest that lipoxin A4 has strong neuroprotective effects in diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury and that the underlying mech-anism is related to the anti-inlfammatory action of lipoxin A4.

  9. Protective Effect of Extract of Folium Ginkgo on Repeated Cerebral Ischemia-Reperfusion Injury

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the protective effect of extract of Folium Ginkgo (FGE) on repeated cerebral ischemia-reperfusion injury. Methods: The model in waking mice induced by repeated cerebral ischemia-reperfusion were used in the experiment to observe the effect of FGE on behavior, oxygen free radical metabolism and prostaglandin E2 (PGE2) content by step-through experiment, diving stand and colorimetric method. Results: FGE could obviously improve the learning ability and memory of model animals, and could lower obviously the content of malonyldialdehyde, nitric oxide and PGE2, restore the lowered activity of superoxide dismutase and catalase in cerebral tissue. Conclusion: FGE has highly protective effect against repeated ischemia-reperfusion injury, the mechanism might be related with its action on anti-lipid oxidatin, improve the activity of antioxidase and inhibit the producing of PGE2.

  10. 肢体缺血再灌注损伤的新型动物模型制作%New animal model making of limb ischemia reperfusion

    Institute of Scientific and Technical Information of China (English)

    王崇文; 姑丽巴哈尔·吾布力; 田禾; 加莎热特·杰力勒; 艾合买提江·玉素甫; 田征

    2012-01-01

    [ Objective] Pneumatic tourniquet was used to make limb ischemia reperfusion of animal model to investigate the injury of peripheral nerve and the skeletal muscle. [ Method ] Thirty health 6-raonth-old New Zealand white rabbits( weighing 3. 5 ±0.3 kg, male or female) were choosen,the left hind limb in rabbits was circled with inflatable tourniquet release at different times, resulting in the left hind limb ischemia-reperfusion injury model. Animals were randomly divided into 3 groups of 10 each, group A; a control group B: ischemia for 2 hours, group C: ischemia for 4 hours. Except group A all the groups were circled with inflatable tourniquet. Each group were measured with indicators of limb eleutrophysiology reperfusion after 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours. The muscle of group A was observed by morphology after 6 hours. The muscle of group B and C were observed by morphology 6 hours after reperfusion. The walking function of left hind limb of every rabbits was evaluated 5 days after surgery. [Result] With the longing of ischemia-reperfusiun time, the incubation period of the peripheral nerves extended,amplitude lowered and conduction velocity decreased in groups B,C compered with group A. The incubation , amplitude and conduction velocity among three groups had statistically significant difference (P < 0.05). Skeletal muscle under microscopy (group B and C) showed stripes disorders, muscle fiber rupture, interstitial vascular dilatation and congestion , and a large number of neutrophils infiltration. [ Conclusion ] After the interaction of ischemia and reperfusion, the physical damage cound further increase the functionality, or even lead to irreversible lesions. The animal model making has less damage to animals, and is similar to clinical practice.%[目的]用充气止血带制作肢体缺血再灌注损伤的新型动物模型,研究其对周围神经和骨骼肌损伤的影响.[方法]选择健康新西兰大白兔6个月龄,30

  11. Hydrogen sulfide intervention in focal cerebral ischemia/reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Xin-juan Li

    2015-01-01

    Full Text Available The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X 7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X 7 receptors.

  12. Lateral intracerebroventricular injection of Apelin-13 inhibits apoptosis after cerebral ischemia/reperfusion injury

    Directory of Open Access Journals (Sweden)

    Xiao-ge Yan

    2015-01-01

    Full Text Available Apelin-13 inhibits neuronal apoptosis caused by hydrogen peroxide, yet apoptosis following cerebral ischemia-reperfusion injury has rarely been studied. In this study, Apelin-13 (0.1 µg/g was injected into the lateral ventricle of middle cerebral artery occlusion model rats. TTC, TUNEL, and immunohistochemical staining showed that compared with the cerebral ischemia/reperfusion group, infarct volume and apoptotic cell number at the ischemic penumbra region were decreased in the Apelin-13 treatment group. Additionally, Apelin-13 treatment increased Bcl-2 immunoreactivity and decreased caspase-3 immunoreactivity. Our findings suggest that Apelin-13 is neuroprotective against cerebral ischemia/reperfusion injury through inhibition of neuronal apoptosis.

  13. Hydrogen sulfide intervention in focal cerebral ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Li, Xin-Juan; Li, Chao-Kun; Wei, Lin-Yu; Lu, Na; Wang, Guo-Hong; Zhao, Hong-Gang; Li, Dong-Liang

    2015-06-01

    The present study aimed to explore the mechanism underlying the protective effects of hydrogen sulfide against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulfide donor compound sodium hydrosulfide. Immunofluorescence revealed that the immunoreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treatment of these rats with hydrogen sulfide significantly lowered mortality, the Longa neurological deficit scores, and infarct volume. These results indicate that hydrogen sulfide may be protective in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.

  14. Effect of morphine preconditioning on neuronal apoptosis following cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    He Dong; Xiangyu Ji; Dong Wang; Yueyi Ren; Shiduan Wang; Jianfang Song

    2010-01-01

    Apoptosis,a form of neuronal damage,takes place following cerebral ischemia/reperfusion injury,and caspase-3 plays an important role in apoptosis.Studies have shown that morphine preconditioning influences neuronal apoptosis and related protein expression following cerebral ischemia/reperfusion injury.In the present study,neuronal degeneration was attenuated,and the number of apoptotic cells and caspase-3 expression decreased following morphine preconditioning in a rat model of cerebral ischemia/reperfusion injury.Moreover,pathological changes were attenuated with increasing morphine doses,as well as the number of apoptotic cells and caspase-3 expression.Results from the present study revealed that morphine preconditioning reduced ischemic brain injury and improved cerebral ischemic tolerance in a dose-dependent manner.The anti-apoptotic mechanism of morphine is closely related to Caspase-3.

  15. Hydrogen sulifde intervention in focal cerebral ischemia/reperfusion injur y in rats

    Institute of Scientific and Technical Information of China (English)

    Xin-juan Li; Chao-kun Li; Lin-yu Wei; Na Lu; Guo-hong Wang; Hong-gang Zhao; Dong-liang Li

    2015-01-01

    The present study aimed to explore the mechanism underlying the protective effects of hydro-gen sulifde against neuronal damage caused by cerebral ischemia/reperfusion. We established the middle cerebral artery occlusion model in rats via the suture method. Ten minutes after middle cerebral artery occlusion, the animals were intraperitoneally injected with hydrogen sulifde donor compound sodium hydrosulifde. Immunolfuorescence revealed that the immu-noreactivity of P2X7 in the cerebral cortex and hippocampal CA1 region in rats with cerebral ischemia/reperfusion injury decreased with hydrogen sulfide treatment. Furthermore, treat-ment of these rats with hydrogen sulifde signiifcantly lowered mortality, the Longa neurological deifcit scores, and infarct volume. These results indicate that hydrogen sulifde may be protec-tive in rats with local cerebral ischemia/reperfusion injury by down-regulating the expression of P2X7 receptors.

  16. Lateral intracerebroventricular injection of Apelin-13 inhibits apoptosis after cerebral ischemia/reperfusion injur y

    Institute of Scientific and Technical Information of China (English)

    Xiao-ge Yan; Bao-hua Cheng; Xin Wang; Liang-cai Ding; Hai-qing Liu; Jing Chen; Bo Bai

    2015-01-01

    Apelin-13 inhibits neuronal apoptosis caused by hydrogen peroxide, yet apoptosis following cerebral ischemia-reperfusion injury has rarely been studied. In this study, Apelin-13 (0.1 μg/g) was injected into the lateral ventricle of middle cerebral artery occlusion model rats. TTC, TUNEL, and immuno-histochemical staining showed that compared with the cerebral ischemia/reperfusion group, infarct volume and apoptotic cell number at the ischemic penumbra region were decreased in the Apelin-13 treatment group. Additionally, Apelin-13 treatment increased Bcl-2 immunoreactivity and decreased caspase-3 immunoreactivity. Our ifndings suggest that Apelin-13 is neuroprotective against cerebral ischemia/reperfusion injury through inhibition of neuronal apoptosis.

  17. Exogenous surfactant application in a rat lung ischemia reperfusion injury model: effects on edema formation and alveolar type II cells

    Directory of Open Access Journals (Sweden)

    Richter Joachim

    2008-01-01

    Full Text Available Abstract Background Prophylactic exogenous surfactant therapy is a promising way to attenuate the ischemia and reperfusion (I/R injury associated with lung transplantation and thereby to decrease the clinical occurrence of acute lung injury and acute respiratory distress syndrome. However, there is little information on the mode by which exogenous surfactant attenuates I/R injury of the lung. We hypothesized that exogenous surfactant may act by limiting pulmonary edema formation and by enhancing alveolar type II cell and lamellar body preservation. Therefore, we investigated the effect of exogenous surfactant therapy on the formation of pulmonary edema in different lung compartments and on the ultrastructure of the surfactant producing alveolar epithelial type II cells. Methods Rats were randomly assigned to a control, Celsior (CE or Celsior + surfactant (CE+S group (n = 5 each. In both Celsior groups, the lungs were flush-perfused with Celsior and subsequently exposed to 4 h of extracorporeal ischemia at 4°C and 50 min of reperfusion at 37°C. The CE+S group received an intratracheal bolus of a modified natural bovine surfactant at a dosage of 50 mg/kg body weight before flush perfusion. After reperfusion (Celsior groups or immediately after sacrifice (Control, the lungs were fixed by vascular perfusion and processed for light and electron microscopy. Stereology was used to quantify edematous changes as well as alterations of the alveolar epithelial type II cells. Results Surfactant treatment decreased the intraalveolar edema formation (mean (coefficient of variation: CE: 160 mm3 (0.61 vs. CE+S: 4 mm3 (0.75; p 3 (0.90 vs. CE+S: 0 mm3; p 3 (0.39 vs. CE+S: 268 mm3 (0.43; p 3(0.10 and CE+S (481 μm3(0.10 compared with controls (323 μm3(0.07; p Conclusion Intratracheal surfactant application before I/R significantly reduces the intraalveolar edema formation and development of atelectases but leads to an increased development of

  18. Evaluation of the gender difference in the protective effects of ischemic postconditioning on ischemia-reperfusion-induced acute kidney injury in rats

    Directory of Open Access Journals (Sweden)

    Atefeh Mahmoudi

    2013-11-01

    Full Text Available Background: Several studies indicate that gender differences exist in tolerance of the kidney to ischemia reperfusion (IR injury. Recently, postconditioning (POC, induction of brief repetitive periods of IR, has been introduced to reduce the extent of the damage to the kidney. This method was shown to attenuate renal IR injury by modifying oxidative stress and reducing lipid peroxidation. Considering the gender effect on the results of several treatment methods, in this study, we investigated the impact of gender on the protective effect of POC on the rat kidney.Methods: In this study, after right nephrectomy, 48 male and female rats were randomly divided into 6 groups of 8 rats: In IR group, with the use of bulldog clamp, 45 minutes of left renal artery ischemia was induced followed by 24 hours of reperfusion. In the sham group, all of the above surgical procedures were applied except that IR was not induced. In the POC group, after the induction of 45 minutes ischemia, 4 cycles of 10 seconds of intermittent ischemia and reperfusion were applied before restoring of blood to the kidney. 24 hours later, serum and renal tissue samples were collected for renal functional monitoring and oxidative stress evaluation.Results: Postconditioning attenuated renal dysfunction considering the significant decrease in plasma creatinine and BUN compared with IR group only in male rats (P<0.05. Also, POC attenuated oxidative stress in male rats’ kidney tissues as demonstrated by a significantly reduced malondialdehyde (MDA level and increased superoxide dismutase (SOD activity (P<0.05. In female rats, there were no changes in functional markers and oxidative stress status in POC group compared to IR group. Conclusion: Considering gender difference, POC had protective effect against IR injury by attenuating functional and oxidative stress markers in male rat kidneys. This protective effect was not seen in female rats.

  19. Transcription factor changes following long term cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Hongbo Zhang; Weijuan Gao; Tao Qian; Jinglong Tang; Jun Li

    2013-01-01

    The present study established a rat model of cerebral ischemia/reperfusion injury using four-vessel occlusion and found that hippocampal CA1 neuronal morphology was damaged, and that there were reductions in hippocampal neuron number and DNA-binding activity of cAMP response element binding protein and CCAAT/enhancer binding protein, accompanied by decreased learning and memory ability. These findings indicate that decline of hippocampal cAMP response element binding protein and CCAAT/enhancer binding protein DNA-binding activities may contribute to neuronal injury and learning and memory ability reduction induced by cerebral ischemia/reperfusion injury.

  20. Lazaroid U-74389G Administration in Pancreatic Ischemia-Reperfusion Injury: A Swine Model Encompassing Ischemic Preconditioning

    Directory of Open Access Journals (Sweden)

    Dimosthenis T Chrysikos

    2015-05-01

    Full Text Available Context The potential of lazaroid U-74389G in attenuating injury after ischemia and reperfusion has been reported in various organs. Objective The present study focuses specifically on the pancreas and aims to examine any effects of U-74389G in a swine model of pancreatic ischemia and reperfusion, encompassing ischemic preconditioning. Methods Twelve pigs, weighing 28–35 kg, were randomized into two experimental groups. Group A (control group, n=6: Two periods of ischemic preconditioning (5 min each separated by a 5- min rest interval; then ischemia time 30 min and reperfusion for 120 min. Group B (n=6: the same as above, with U-74389G intravenous injection in the inferior vena cava immediately prior to the initiation of reperfusion. Blood sampling and pancreatic biopsies were conducted at 0, 30, 60, 90 and 120 min after reperfusion. Results Repeated-measures ANOVA was undertaken to evaluate differences between the two study groups. No statistically significant differences were noted concerning the histopathological parameters in the control and therapygroups (P=0.563 for edema, P=0.241 for hemorrhage, P=0.256 for leukocyte infiltration, P=0.231 for acinar necrosis and P=0.438 for vacuolization. In accordance with the above, serum metabolic data (glucose, creatinine, urea, total and direct bilirubin, total calcium, amylase, lipase, SGOT/AST, SGPT/ALT, ALP, GGT, LDH, CRP, insulin were not significantly different between the two groups; similarly, tumor necrosis factor-α values (P=0.705 and tissue malondialdehyde levels (P=0.628 did not differ between the two groups. Conclusion This swine model of pancreatic ischemia and reperfusion, encompassing preconditioning, indicates that U-74389G lazaroid does not seem to exert protective effects from pancreatic damage.

  1. The Effect of Nitric Oxide/Endothelins System on the Hepatic Ischemia/Reperfusion Injury

    Institute of Scientific and Technical Information of China (English)

    吕平; 陈道达; 田源; 张景辉; 吴毅华

    2002-01-01

    Summary: The relationship between the hepatic ischemia/reperfusion (I/R) injury and the balance of nitric oxide/endothelins (NO/ET) was studied. The changes of the ratio of NO/ET and the hepatic injury were observed in a rat hepatic I/R model pretreated with several tool drugs. In the acute phase of hepatic I/R injury, the ratio of plasma NO/ET was reduced from 1.58 ± 0. 20 to 0. 29 ± 0. 05 (P < 0. 01) and the hepatic damage deteriorated. NO donor L-Arg and ET receptor antagonist TAK-044 could alleviate the hepatic I/R injury to some degree, whereas NO synthase inhibitor L-NAME aggravated the damage. It was concluded that the hepatic I/R injury might be related with the disturbance of the NO/ET balance. Regulation of this balance might have an effect on the I/R injury.

  2. Cerebral Ischemia Reperfusion Exacerbates and Pueraria Flavonoids Attenuate Depressive Responses to Stress in Mice

    Institute of Scientific and Technical Information of China (English)

    LAN Jiaqi; YAN Bin; ZHAO Yu'nan; WANG Daoyi; HU Jun; XING Dongming; DU Lijun

    2008-01-01

    Previous studies have shown that mice experiencing cerebral ischemia reperfusion (CIR) and stress can serve as a model of post stroke depression (PSD).The present study verified the acute antide-pressant effects of radix puerariae extract (PE) on PSD mice through behavior and gene expression ex-periments.CIR was found to reduce the sucrose consumption and tyrosine hydroxylase (TH) gene expres-sion.PE administration after CIR surgery was observed to significantly enhance the mRNA expression of TH in the hippocampus compared with the PSD group on Day 0 and Day 3 postsurgery.These findings in-dicate that PE contributes to the amelioration of behavior response in PSD mice,which is closely related with the protective effects of catecholamine synthesize against CIR brain damage.

  3. Sodium Hypochlorite-Modified Hemosorbents in the Treatment of Limb Ischemia-Reperfusion Syndrome: Experimental Study

    Directory of Open Access Journals (Sweden)

    V. I. Sergiyenko

    2007-01-01

    Full Text Available Objective: to enhance the efficiency of treatment for limb ischemia-reperfusion syndrome in an experiment, by using the modified hemosorbents that have oxidative properties.Materials and methods. The investigation was conducted on 94 mongrel male dogs divided into 3 groups: 1 intact animals (n=20; 2 animals treated with hemocarboperfusion on the standard sorbent CKH-1K (n=36; 3 animals received hemocarboperfusion on sodium hypochloride-modified sorbent CKH-1K (n=38. A model of acute ischemia-reperfusion syndrome was created by the method of V. D. Pasechnikov et al. Partial oxygen tension (pO2 was determined by pin polarography. The levels of vasoactive eicosanoids were measured by enzyme immunoassay.Results. In the animals with leg ischemia syndrome, there is a significant pO2 reduction in the muscles of the hip and shin, which does not completely recover after reperfusion. Standard CKN-1K sorbent hemocarboperfusion reduces pO2 as compared with the reperfusion period while the use of modified CKH-1K hemosorbent increased pO2 in the study hind limb muscles to the level observed in intact animals. The development of ischemia and reperfusion is accompanied by the elevated levels of inflammatory mediators that have vasoconstrictive properties (thromboxane B2, endothelin-1, leukotrienes C4/D4/E4 and the lower concentration of the vasodilator prostacyclin. Standard CKN-1K sorbent hemocarboperfusion results in a further increase in the concentrations of thromboxane B2 and leukotrienes C4/D4/E4, a decrease in the concentration of endothelin-1, and an elevation of the levels of prostacyclin and prostaglandin E2. When sodium hypochlorite-modified CKN-1K sorbent hemocarboperfusion is employed, the concentrations of thromboxane B2, endothelin-1, and leukotrienes C4/D4/E4 decrease, and the level of prostacyclin increases.Conclusion. Hemocarboperfusion used in the treatment of leg ischemia-reperfusion syndrome leads to restoration of tissue oxygenation and

  4. Matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Lifang Lei; Xiaohong Zi; Qiuyun Tu

    2008-01-01

    BACKGROUND: The integrity of the blood brain barrier (BBB) plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 (MMP-9) is closely related to cerebral ischemia/reperfusion injuryOBJECTIVE: This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability.DESIGN, TIME AND SETTING: This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006.MATERIALS: Ninety healthy male SD rats, aged 3-4 months, weighing 200-280g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody (Boster, Wuhan, China) and Evans blue (Sigma, USA) were also used.METHODS: All rats were randomly divided into 9 groups with 10 rats in each group: normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3,6,12 hours, 1,2,4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled.MAIN OUTCOME MEASURES: BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method.RESULTS: All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter

  5. Renoprotective capacities of non-erythropoietic EPO derivative, ARA290, following renal ischemia/reperfusion injury

    NARCIS (Netherlands)

    van Rijt, Willem G; Nieuwenhuijs-Moeke, Gertrude J; van Goor, Harry; Ottens, Petra J; Ploeg, Rutger J; Leuvenink, Henri G D

    2013-01-01

    Background: ARA290 is a non-erythropoietic EPO derivative which only binds to the cytoprotective receptor complex (EPOR2-beta cR(2)) consisting of two EPO-receptors (EPOR) and two beta common receptors (beta cR). ARA290 is renoprotective in renal ischemia/reperfusion (I/R). In a renal I/R model we f

  6. Treatment of Tourniquet-Induced Ischemia Reperfusion Injury with Muscle Progenitor Cells

    Science.gov (United States)

    2011-09-01

    Weinstein AL, et al. Therapeutic met- abolic inhibition: Hydrogen sulfide significantly mitigates skele- tal muscle ischemia reperfusion injury in vitro...muscle function in animal models of muscular diseases, dener- vation, toxins , cryo-injuries, and volumetricmuscle loss [21–24], and have been used to

  7. Danhong injection A modulator for Golgi structural stability after cerebral ischemia-reperfusion injury*

    Institute of Scientific and Technical Information of China (English)

    Yan Wang; Zhiping Hu; Wei Lu

    2013-01-01

    The cerebral ischemia-reperfusion model was established using the suture occlusion method, and rats were intraperitoneal y given 8 mL/kg Danhong injection once a day prior to model establishment. Rat brain tissues were harvested at 6, 24, 48, 72 hours after reperfusion. Immunohistochemical staining showed that transforming growth factor-β1 expression increased, while Golgi matrix protein GM130 expression decreased after cerebral ischemia-reperfusion. Danhong injection was shown to significantly up-regulate the expression of transforming growth factor-β1 and GM130, and expres-sion levels peaked at 7 days after reperfusion. At 7 days after cerebral ischemia-reperfusion, Golgi morphology was damaged in untreated rats, while Golgi morphology breakage was not observed after intervention with Danhong injection. These experimental findings indicate that Danhong injec-tion can up-regulate the expression of transforming growth factor-β1 and GM130, and maintain Golgi stability, thus playing a neuroprotective role in rats after cerebral ischemia-reperfusion.

  8. Antioxidant effects of xanthohumol and functional impact on hepatic ischemia-reperfusion injury.

    Science.gov (United States)

    Hartkorn, Andreas; Hoffmann, Florian; Ajamieh, Hussam; Vogel, Susanne; Heilmann, Jörg; Gerbes, Alexander L; Vollmar, Angelika M; Zahler, Stefan

    2009-10-01

    Therapeutic effects of dietary flavonoids have been attributed mainly to their antioxidant capacity. Xanthohumol (1), a prominent flavonoid of the hop plant, Humulus lupulus, was investigated for its antioxidant potential and for its effect on NF-kappaB activation. To examine the biological relevance of 1, a hepatic ischemia/reperfusion model was chosen as a widely accepted model of oxidative stress generation. The impact of 1 on endogenous antioxidant systems, on the NF-kappaB signal transduction pathway as well as on apoptotic parameters, and on hepatic tissue damage was evaluated. Compound 1 markedly decreased the level of reactive oxygen species in vitro. Furthermore, levels of enzymatic and nonenzymatic antioxidants were restored after pretreatment in postischemic hepatic tissue, and lipid peroxidation was attenuated. NF-kappaB activity was reduced in vitro as well as in hepatic tissue after ischemia/reperfusion upon pretreatment with 1. In addition, the phosphorylation of Akt was markedly inhibited. Surprisingly, 1 decreased the expression of the antiapoptotic protein Bcl-X and increased caspase-3 like-activity, a proapoptotic parameter. Moreover, hepatic tissue damage as well as TNF-alpha levels increased in xanthohumol-pretreated liver tissue after ischemia/reperfusion. In summary, xanthohumol did not protect against ischemia/reperfusion injury in rat liver, despite its antioxidant and NF-kappaB inhibitory properties.

  9. Sesamin protects against renal ischemia reperfusion injury by promoting CD39-adenosine-A2AR signal pathway in mice.

    Science.gov (United States)

    Li, Ke; Gong, Xia; Kuang, Ge; Jiang, Rong; Wan, Jingyuan; Wang, Bin

    2016-01-01

    Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury with high morbidity and mortality due to limited therapy. Here, we examine whether sesamin attenuates renal IRI in an animal model and explore the underlying mechanisms. Male mice were subjected to right renal ischemia for 30 min followed by reperfusion for 24 h with sesamin (100 mg/kg) during which the left kidney was removed. Renal damage and function were assessed subsequently. The results showed that sesamin reduced kidney ischemia reperfusion injury, as assessed by decreased serum creatinine (Scr) and Blood urea nitrogen (BUN), alleviated tubular damage and apoptosis. In addition, sesamin inhibited neutrophils infiltration and pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β production in IR-preformed kidney. Notably, sesamin promoted the expression of CD39, A2A adenosine receptor (A2AAR), and A2BAR mRNA and protein as well as adenosine production. Furthermore, CD39 inhibitor or A2AR antagonist abolished partly the protection of sesamin in kidney IRI. In conclusion, sesamin could effectively protect kidney from IRI by inhibiting inflammatory responses, which might be associated with promoting the adenosine-CD39-A2AR signaling pathway.

  10. σ1-Receptor Agonism Protects against Renal Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Hosszu, Adam; Antal, Zsuzsanna; Lenart, Lilla; Hodrea, Judit; Koszegi, Sandor; Balogh, Dora B; Banki, Nora F; Wagner, Laszlo; Denes, Adam; Hamar, Peter; Degrell, Peter; Vannay, Adam; Szabo, Attila J; Fekete, Andrea

    2017-01-01

    Mechanisms of renal ischemia-reperfusion injury remain unresolved, and effective therapies are lacking. We previously showed that dehydroepiandrosterone protects against renal ischemia-reperfusion injury in male rats. Here, we investigated the potential role of σ1-receptor activation in mediating this protection. In rats, pretreatment with either dehydroepiandrosterone or fluvoxamine, a high-affinity σ1-receptor agonist, improved survival, renal function and structure, and the inflammatory response after sublethal renal ischemia-reperfusion injury. In human proximal tubular epithelial cells, stimulation by fluvoxamine or oxidative stress caused the σ1-receptor to translocate from the endoplasmic reticulum to the cytosol and nucleus. Fluvoxamine stimulation in these cells also activated nitric oxide production that was blocked by σ1-receptor knockdown or Akt inhibition. Similarly, in the postischemic rat kidney, σ1-receptor activation by fluvoxamine triggered the Akt-nitric oxide synthase signaling pathway, resulting in time- and isoform-specific endothelial and neuronal nitric oxide synthase activation and nitric oxide production. Concurrently, intravital two-photon imaging revealed prompt peritubular vasodilation after fluvoxamine treatment, which was blocked by the σ1-receptor antagonist or various nitric oxide synthase blockers. In conclusion, in this rat model of ischemia-reperfusion injury, σ1-receptor agonists improved postischemic survival and renal function via activation of Akt-mediated nitric oxide signaling in the kidney. Thus, σ1-receptor activation might provide a therapeutic option for renoprotective therapy.

  11. Pretreatment with scutellaria baicalensis stem-leaf total flavonoid prevents cerebral ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Shumin Zhao; Wei Kong; Shufeng Zhang; Meng Chen; Xiaoying Zheng; Xiangyu Kong

    2013-01-01

    Pretreatment with scutel aria baicalensis stem-leaf total flavonoid has protective effects against ischemia and attenuates myocardial ischemia-reperfusion injury. In this study, rats were given scu-tel aria baicalensis stem-leaf total flavonoid intragastrical y at 50, 100, and 200 mg/kg per day for 7 days before focal cerebral ischemia-reperfusion injury models were established using the suture method. We then determined the protective effects of scutel aria baicalensis stem-leaf total flavo-noid pretreatment on focal cerebral ischemia-reperfusion injury. Results showed that neurological deficit scores increased, infarct volumes enlarged, apoptosis increased and Bcl-2 and Bax protein expression were upregulated at 24 hours after reperfusion. Pretreatment with scutel aria baicalensis stem-leaf total flavonoid at any dose lowered the neurological deficit scores, reduced the infarct volume, prevented apoptosis in hippocampal cells, attenuated neuronal and blood-brain barrier damage and upregulated Bcl-2 protein expression but inhibited Bax protein expression. Doses of 100 and 200 mg/kg were the most efficacious. Our findings indicate that pretreatment with scutel a-ria baicalensis stem-leaf total flavonoid at 100 and 200 mg/kg can improve the neurological func-tions and have preventive and protective roles after focal cerebral ischemia-reperfusion injury.

  12. The effect of mitochondrial calcium uniporter on mitochondrial fission in hippocampus cells ischemia/reperfusion injury

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Lantao; Li, Shuhong; Wang, Shilei, E-mail: wshlei@aliyun.com; Yu, Ning; Liu, Jia

    2015-06-05

    The mitochondrial calcium uniporter (MCU) transports free Ca{sup 2+} into the mitochondrial matrix, maintaining Ca{sup 2+} homeostasis, thus regulates the mitochondrial morphology. Previous studies have indicated that there was closely crosstalk between MCU and mitochondrial fission during the process of ischemia/reperfusion injury. This study constructed a hypoxia reoxygenation model using primary hippocampus neurons to mimic the cerebral ischemia/reperfusion injury and aims to explore the exactly effect of MCU on the mitochondrial fission during the process of ischemia/reperfusion injury and so as the mechanisms. Our results found that the inhibitor of the MCU, Ru360, decreased mitochondrial Ca{sup 2+} concentration, suppressed the expression of mitochondrial fission protein Drp1, MIEF1 and Fis1, and thus improved mitochondrial morphology significantly. Whereas spermine, the agonist of the MCU, had no significant impact compared to the I/R group. This study demonstrated that the MCU regulates the process of mitochondrial fission by controlling the Ca{sup 2+} transport, directly upregulating mitochondrial fission proteins Drp1, Fis1 and indirectly reversing the MIEF1-induced mitochondrial fusion. It also provides new targets for brain protection during ischemia/reperfusion injury. - Highlights: • We study MCU with primary neuron culture. • MCU induces mitochondrial fission. • MCU reverses MIEF1 effect.

  13. The effect of mitochondrial calcium uniporter on mitochondrial fission in hippocampus cells ischemia/reperfusion injury.

    Science.gov (United States)

    Zhao, Lantao; Li, Shuhong; Wang, Shilei; Yu, Ning; Liu, Jia

    2015-06-01

    The mitochondrial calcium uniporter (MCU) transports free Ca(2+) into the mitochondrial matrix, maintaining Ca(2+) homeostasis, thus regulates the mitochondrial morphology. Previous studies have indicated that there was closely crosstalk between MCU and mitochondrial fission during the process of ischemia/reperfusion injury. This study constructed a hypoxia reoxygenation model using primary hippocampus neurons to mimic the cerebral ischemia/reperfusion injury and aims to explore the exactly effect of MCU on the mitochondrial fission during the process of ischemia/reperfusion injury and so as the mechanisms. Our results found that the inhibitor of the MCU, Ru360, decreased mitochondrial Ca(2+) concentration, suppressed the expression of mitochondrial fission protein Drp1, MIEF1 and Fis1, and thus improved mitochondrial morphology significantly. Whereas spermine, the agonist of the MCU, had no significant impact compared to the I/R group. This study demonstrated that the MCU regulates the process of mitochondrial fission by controlling the Ca(2+) transport, directly upregulating mitochondrial fission proteins Drp1, Fis1 and indirectly reversing the MIEF1-induced mitochondrial fusion. It also provides new targets for brain protection during ischemia/reperfusion injury.

  14. Ischemia reperfusion injury, ischemic conditioning and diabetes mellitus.

    Science.gov (United States)

    Lejay, Anne; Fang, Fei; John, Rohan; Van, Julie A D; Barr, Meredith; Thaveau, Fabien; Chakfe, Nabil; Geny, Bernard; Scholey, James W

    2016-02-01

    Ischemia/reperfusion, which is characterized by deficient oxygen supply and subsequent restoration of blood flow, can cause irreversible damages to tissue. Mechanisms contributing to the pathogenesis of ischemia reperfusion injury are complex, multifactorial and highly integrated. Extensive research has focused on increasing organ tolerance to ischemia reperfusion injury, especially through the use of ischemic conditioning strategies. Of morbidities that potentially compromise the protective mechanisms of the heart, diabetes mellitus appears primarily important to study. Diabetes mellitus increases myocardial susceptibility to ischemia reperfusion injury and also modifies myocardial responses to ischemic conditioning strategies by disruption of intracellular signaling responsible for enhancement of resistance to cell death. The purpose of this review is twofold: first, to summarize mechanisms underlying ischemia reperfusion injury and the signal transduction pathways underlying ischemic conditioning cardioprotection; and second, to focus on diabetes mellitus and mechanisms that may be responsible for the lack of effect of ischemic conditioning strategies in diabetes.

  15. 七氟醚预处理对大鼠急性肾缺血-再灌注损伤保护作用的实验研究%Sevoflurane preconditioning on the experimental study on the protective effects of acute renal ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    田德明; 叶虹; 冯微

    2014-01-01

    Objective To explore the protective effects of sevoflurane on renal function in acute renal ischemia-reperfusion injury.Methods 90 healthy SD rats were randomly divided into three groups:sham-operated group,control group,sevoflurane inhalated group.Acute renal ischemia reperfusion model were established by clamping the renal pedi-cle.Mean arterial pressure(MAP),partial pressure of carbon dioxide(PCO2 ),blood urea nitrogen(BUN),creatinine (Cr)and superoxide dismutas-e(SOD)levels were determined in each groups,the renal pathological changes were ob-served by HE staining.Results With the increase in the concentration ofsevoflurance,the mean arterial pressure of the rats decreased,But the usual clinical doses in the range of sevoflurane concentration in 2%-3%,MAP is 92.1 ± 6.0 mmHg.There is no significant difference of PCO2 concentration in each group before ischemia and after reperfusion.Af-ter renal ischemia reperfusion 12 h,24 h,the BUN and Cr levels of control group and sevoflurane inhalated group were significantly higher than that in sham-operated group (P <0.05),but the BUN,Cr levels of sevoflurane inhalated group were decreased significantly compared with B group (P <0.05).Compared with sham-operated group,the serum SOD activity of control group and sevoflurane inhalated group were significantly decreased (P <0.05),But the activity of SOD of sevoflurane inhalated group was higher than control group (P < 0.05).The renal pathological structure of sham-operated group was integrity,the damage of renal outer medullary tissue was severly in control group,but the sevoflurane inhalated group kidney tubular tissue damage were lightly.Conclusion Sevoflurane inhalation anesthesia can effectively reduce BUN,Cr level,protect SOD activity,and thus,has a protective effect on renal function on acute renal ischemia/reperfusion injury.%目的:探索七氟醚对急性肾缺血-再灌注损伤肾功能的保护作用。方法选择健康 SD 大鼠90只,随机分为三组:

  16. Silencing CHOP Gene gene Reduced reduced The the Acute acute Brain brain Injury injury in Cerebral cerebral Ischemia ischemia Reperfusion reperfusion in rRats%沉默CHOP基因减轻脑缺血再灌注大鼠的急性脑损伤

    Institute of Scientific and Technical Information of China (English)

    郑胜哲; 谷月; 何春珂; 王婷婷; 贾丽君

    2013-01-01

    目的 研究大鼠脑缺血再灌注后急性脑损伤中CHOP蛋白的作用.方法 将36只SD大鼠随机分为对照组、vector组和LV-shRNA组,经微型注射泵向control组左脑室中注射PBS,vector组注射入LV-CMV-control 质粒,向LV-shRNA组注射入LV-CMV-CHOP shRNA质粒.线栓法制作大鼠缺血再灌注模型后,TTC染色检测各组大鼠脑梗死体积,Western Blot检测所有大鼠脑内CHOP、Bcl-2和Caspase 3的表达,TUNEL染色检测梗死区细胞凋亡.结果 LV-shRNA组大鼠脑梗死体积明显小于对照组和vector组(P<0.01);Western Blot结果显示LV-shRNA组大鼠脑内CHOP和Caspase3含量明显低于对照组和vector组(P<0.01),而Bcl-2高于对照组和vector组(P>0.05);TUNEL染色显示LV-shRNA组大鼠脑梗死区域内凋亡细胞明显少于对照组和vector组(P<0.01).结论 CHOP在脑缺血后具有促进急性脑损伤的作用,沉默CHOP可通过减轻细胞凋亡反应发挥神经保护作用.%Objective ive To investigate the role of CHOP in the acute cerebral injury in rats with focal cerebral ischemia/reperfusion. Methods 36 rats were randomly divided into control group, vector group and LV-shRNA group. PBS was injected into the left ventricle of rats in control group via micro-injection pump,whereas LV-CMV-control plasmid and LV-CMV-CHOP shRNA plasmid were injected into the rats brain of vector group and LV-CMV-control group respectively. The animal model of the left MCA ischemia/reperfusion was established by suture method. Cerebral infarct volume was measured by TTC staining and the expression of CHOP, Bcl-2 and Caspase 3 in rats brain were detected by Western Blot-blot. In addition,TUNEL staining was utilized to examine cell apoptosis in infarct zone. Results The infarction volume of rats in LV-shRNA group was obviously less than control group and vector group (P 0.05). TUNEL staining showed that the apoptosis cells in LV-shRNA group rats' infarction area was markedly less than those in control

  17. The protecting effects and mechanism of betaine hydrochloride on hepatic ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    XIN Xiao-ming; MA Lian-long; GAO Yong-feng; WANG Hao; WANG Xiao-dan; ZHU Yu-yun; GAO Yun-sheng

    2008-01-01

    Objective To study the protecting effects and mechanism of betaine hydrochloride on hepatic ischemia-reperfusion injury in rats. Methods Fourty SD rats were randomly divided into 5 groups (8 animals in each group) : sham-operated control group (A), hepatic ischemia-reperfusion group (B), 200 mg·kg-1 400 mg·kg-1 800 mg·kg-1 betaine hydrochloride + hepatic ischemia-reperfusion group (C、D、E). betaine hydrochloride was administered to animals byoral route in group C、D、E for 7 days before ischemia. A、B group was administered with NS. Made the animal model of part hepatic ischemia-reperfusion. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels in the blood and themalondialdehyde (MDA), superoxide dismutase (SOD), protein content in hepatic tissue were determined after the liver had been reperfused for 24 hours; the hepatic tissue was examined under lightmieroscope and the cell apoptosis was demonstrated with flow cytometry. Results ALT, AST, MDA increased and SOD decreased significantly in B group when compared those in the A group (P<0.05), Hepatic apoptosis was significantly increased; ALT, AST, MDA decreased and SOD increased significantly in betaine hydrochloride 200 mg·kg-1(C) group when compared those in the B group(P<0.05). Hepatic apoptosis was significantly lower, The histologic changes of the liver tissue under lightmicroscope in the C group was more easer than in the I/R group (B). Conclusions Betaine hydrochloride has the ability to scavenge oxygen free radical (OFR), reduce lipid peroxidation and inhibition of apoptosis. So it can protect the rats liver damaged by ischemia-reperfusion.

  18. Anti-inflammatory and Antioxidant Effects of Flavonoid-Rich Fraction of Bergamot Juice (BJe) in a Mouse Model of Intestinal Ischemia/Reperfusion Injury.

    Science.gov (United States)

    Impellizzeri, Daniela; Cordaro, Marika; Campolo, Michela; Gugliandolo, Enrico; Esposito, Emanuela; Benedetto, Filippo; Cuzzocrea, Salvatore; Navarra, Michele

    2016-01-01

    The flavonoid-rich fraction of bergamot juice (BJe) has demonstrated anti-inflammatory and antioxidant activities. The aim of work was to test the beneficial effects of BJe on the modulation of the ileum inflammation caused by intestinal ischemia/reperfusion (I/R) injury in mice. To understand the cellular mechanisms by which BJe may decrease the development of intestinal I/R injury, we have evaluated the activation of signaling transduction pathways that can be induced by reactive oxygen species production. Superior mesenteric artery and celiac trunk were occluded for 30 min and reperfused for 1 h. The animals were sacrificed after 1 h of reperfusion, for both histological and molecular examinations of the ileum tissue. The experimental results demonstrated that BJe was able to reduce histological damage, cytokines production, adhesion molecules expression, neutrophil infiltration and oxidative stress by a mechanism involved both NF-κB and MAP kinases pathways. This study indicates that BJe could represent a new treatment against inflammatory events of intestinal I/R injury.

  19. Anti-inflammatory and antioxidant effects of flavonoid-rich fraction of bergamot juice (BJe in a mouse model of intestinal ischemia/reperfusion injury

    Directory of Open Access Journals (Sweden)

    Daniela Impellizzeri

    2016-07-01

    Full Text Available The flavonoid-rich fraction of bergamot juice (BJe has demonstrated anti-inflammatory and antioxidant activities. The aim of work was to test the beneficial effects of BJe on the modulation of the ileum inflammation caused by intestinal ischemia/reperfusion (I/R injury in mice. To understand the cellular mechanisms by which BJe may decrease the development of intestinal I/R injury, we have evaluated the activation of signaling transduction pathways that can be induced by reactive oxygen species (ROS production. Superior mesenteric artery and celiac trunk were occluded for 30 min and reperfused for 1 h. The animals were sacrificed after 1 h of reperfusion, for both histological and molecular examinations of the ileum tissue. The experimental results demonstrated that BJe was able to reduce histological damage, cytokines production, adhesion molecules expression, neutrophil infiltration and oxidative stress by a mechanism involved both NF-κB and MAP kinases pathways. This study indicates that BJe could represent a new treatment against inflammatory events of intestinal I/R injury.

  20. The Effect of Statins and Other Cardiovascular Medication on Ischemia-Reperfusion Damage in a Human DIEP Flap Model: Theoretical and Epidemiological Considerations

    Directory of Open Access Journals (Sweden)

    M. G. W. van den Heuvel

    2012-01-01

    Full Text Available Background. Statins and other cardiovascular medication possess antioxidant capacity. It was examined whether chronic use of these medications protects from the development of ischemia-reperfusion (I/R related complications after DIEP (Deep Inferior Epigastric Perforator Free Flap surgery. This paper contains a literature study on the antioxidant working mechanisms of these drugs. Methods. Medical information of 134 DIEP patients (173 flaps was studied from their medical files. Patient and operative characteristics were registered, as well as I/R related complications. Results. Of the group that didnot use statins, 16.3% developed complications versus 30.8% amongst patients that did use these drugs (P=0.29. Amongst patients that chronically use other cardiovascular medication, 26.8% developed I/R related complications versus 14.4% of the patients without medication (P=0.10. Conclusions. Chronic use of statins or other cardiovascular medication didnot decrease the occurrence of I/R related complications after DIEP surgery. Therefore, research should be aimed at evaluating short-term pre-treatment with statins.

  1. Memory deficits and oxidative stress in cerebral ischemia-reperfusion: neuroprotective role of physical exercise and green tea supplementation.

    Science.gov (United States)

    Schimidt, Helen L; Vieira, Aline; Altermann, Caroline; Martins, Alexandre; Sosa, Priscila; Santos, Francielli W; Mello-Carpes, Pâmela B; Izquierdo, Ivan; Carpes, Felipe P

    2014-10-01

    Ischemic stroke is a major cause of morbidity and mortality all over the world. Among impairments observed in survivors there is a significant cognitive learning and memory deficit. Neuroprotective strategies are being investigated to minimize such deficits after an ischemia event. Here we investigated the neuroprotective potential of physical exercise and green tea in an animal model of ischemia-reperfusion. Eighty male rats were divided in 8 groups and submitted to either transient brain ischemia-reperfusion or a sham surgery after 8 weeks of physical exercise and/or green tea supplementation. Ischemia-reperfusion was performed by bilateral occlusion of the common carotid arteries during 30 min. Later, their memory was evaluated in an aversive and in a non-aversive task, and hippocampus and prefrontal cortex were removed for biochemical analyses of possible oxidative stress effects. Ischemia-reperfusion impaired learning and memory. Reactive oxygen species were increased in the hippocampus and prefrontal cortex. Eight weeks of physical exercise and/or green tea supplementation before the ischemia-reperfusion event showed a neuroprotective effect; both treatments in separate or together reduced the cognitive deficits and were able to maintain the functional levels of antioxidant enzymes and glutathione.

  2. Total flavonoid of Litsea coreana leve exerts anti-oxidative effects and alleviates focal cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Shuying Dong; Xuhui Tong; Jun Li; Cheng Huang; Chengmu Hu; Hao Jiao; Yuchen Gu

    2013-01-01

    In this study, we hypothesized that total flavonoid of Litsea coreana leve (TFLC) protects against focal cerebral ischemia/reperfusion injury. TFLC (25, 50, 100 mg/kg) was administered oral y to a rat model of focal ischemia/reperfusion injury, while the free radical scavenging agent, edaravone, was used as a positive control drug. Results of neurological deficit scoring, 2,3,5-triphenyl tetrazolium chloride staining, hematoxylin-eosin staining and biochemical tests showed that TFLC at different doses significantly al eviated cerebral ischemia-induced neurological deficits and histopathological changes, and reduced infarct volume. Moreover, it suppressed the increase in the levels of nitrates plus nitrites, malondialdehyde and lactate dehydrogenase, and it diminished the reduction in gluta-thione, superoxide dismutase and catalase activities induced by cerebral ischemia/reperfusion in-jury. Compared with edaravone, the protective effects of TFLC at low and medium doses (25, 50 mg/kg) against cerebral ischemia/reperfusion injury were weaker, while the protective effects at high dose (100 mg/kg) were similar. Our experimental findings suggest that TFLC exerts neuroprotective effects against focal cerebral ischemia/reperfusion injury in rats, and that the effects may be asso-ciated with its antioxidant activities.

  3. Effects of ischemia postconditioning in reducing ischemia reperfusion injury in acute limp ischemia%缺血后适应减轻急性下肢缺血再灌注损伤的实验研究

    Institute of Scientific and Technical Information of China (English)

    李韶南; 黄慧芳; 李广镰; 刘震; 陈平安

    2012-01-01

    目的 观察缺血后适应(IPC)减轻急性下肢缺血(AU)再灌注损伤的疗效并探讨其机制.方法 将45只新西兰大白兔采用高脂饮食与动脉内膜球囊损伤结合的方式建立下肢动脉粥样硬化狭窄动物模型,随机分为对照组、缺血再灌注组(IR组)、缺血后适应组(IPC组),每组各15只.检测三组大白兔阻断股动脉前、持续再灌注2h后血液中肌酸激酶(CK)、丙二醛(MDA)、超氧化物岐化酶(SOD)水平,观察再灌注后下肢骨骼肌组织学改变,并采用原位末端标记法(TUNEL)分析三组大白兔下肢再灌注后骨骼肌细胞凋亡情况.结果 与IR组比较,IPC组兔血浆CK、MDA明显降低[(7.49±0.84) U/L与(8.19±1.06) U/L,P<0.05],[(3.67±0.36) nmol/L与(4.06±0.55) nmol/L,P<0.05],而SOD则显著升高[(420.40±30.94)μmol/L与(384.73±44.12) μmol/L,P<0.05],骨骼肌细胞凋亡指数降低[(12.27±2.11)%与(16.62±1.44)%,P<0.01],差异有统计学意义,并且组织形态学观察IPC组兔骨骼肌损伤、坏死程度较IR组减轻.结论 急性下肢缺血应用IPC能显著减轻下肢缺血再灌注损伤,其机制与减少自由基生成、增强抗氧化及减轻缺血再灌注诱导的骨骼肌细胞凋亡有关.%Objective To study the effects of ischemia postconditioning(IPC) in reducing ischemia-reperfusion injury(IRI) in acute limp ischemia(ALI) and investigate the mechanism.Methods 45 New Zealand rabbits were treated with the method that combined high lipid diets and femoral intima injury by balloon inflation to build up limp atherosclerotic stenosis model,then they were randomly divided into three groups( each group 15 rabbits):control group;IR group and IPC group.Serum creatine phosphate kinase(CK),malondialehyde(MDA),superoxide dismutase (SOD) in three groups were measured before occlusion and 2 hours after sustaining reperfusion.The histological changes of limp skeletal muscle of experimental rabbits were analyzed and TUNEL method was used to

  4. Determination of Urinary Cystatin C in Rats of Ischemia/Reperfusion Acute Kidney Injury%胱抑素C在缺血/再灌注急性肾损伤大鼠尿液中的变化及意义

    Institute of Scientific and Technical Information of China (English)

    戎殳; 李程程; 胡惠民; 蔡彦; 叶朝阳; 梅长林

    2009-01-01

    目的:检测肾缺血/再灌注大鼠尿液胱抑素C含量,探讨其在缺血/再灌注急性肾损伤早期评估中的作用.方法:选取雄性SD大鼠,随机分为4组,建立缺血/再灌注急性肾损伤动物模型,缺血时间4组分别为0、10、20、30 min,测定各组大鼠术前及再灌注24 h后尿液胱抑素C,血清肌酐(Scr)、尿素氮(BUN)浓度,计算24 h肌酐清除率(Ccr),取各组再灌注24 h后肾组织作组织学检查,行肾小管坏死半定量评分.结果:各组大鼠基线肾功能差异无统计学意义,再灌注24 h后与基线值相比,肾缺血0 min组及10 min组BUN、Scr及Ccr无显著改变;肾缺血20 min组BUN、Scr无显著改变,但Ccr显著降低;肾缺血30 min组BUN[(45.3±14.6)vs(13.8±1.6)mmol/L]、Scr[(160.8±22.2)vs(36.9±7.9)μmol/L]显著升高,Ccr显著降低[(1.87±0.3)vs(0.56±0.1)ml/min].20 min组及30 min组肾小管坏死评分与0 rain组相比显著升高.再灌注24 h后与基线值相比,肾缺血0 min组尿液胱抑素C水平无显著改变,肾缺血10 min[(0.79±0.11)、vs(0.25±0.02)μg/L]、20 min[(1.23±0.35)vs,(0.30±0.05)μg/L]及30 min组[(1.33±0.51)vs(0.28±0.03)μg/L]尿液胱抑素C水平显著升高.结论:尿液胱抑素C测定可望成为缺血佴灌注急性肾损伤的早期诊断标记物.%Objective: To determine the urinary cystatin C in rats of ischemia/reperfusion(I/R) acute kidney injury,and to estimate their effects on early diagnosis. Methods: Male SD rats were selected and divided into 4 groups for I/R injury model estab-lishment. The time for bilateral renal artery occlusion were 0,10,20 and 30 rain respectively. The urine cystatin C,serum creatinine (Scr) and BUN of baseline and 24 h after reperfusion were detected.The kidney histological examination 24 h after reperfusion was performed. Results:The basline values of renal function in 4 groups were not different statistically. Compared with those at baseline,at 24 h after reperfusion, BUN, Scr and Ccr did not change

  5. 一种新型实用的大鼠肾缺血再灌注损伤模型的建立%Model construction of renal ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    余晓东; 程树林; 廖波; 邓显忠; 姜果; 朱平宇; 鲁栋梁; 唐铁龙; 杨雪松; 陈双全

    2011-01-01

    Objective To construct a simple and practical model of renal ischemia-reperfusion injury in rats.Methods 48 male Sprague-Dawley rats were randomly divided into two groups : control group(C group) and ischemiareperfusion group(IK group) ,the four phases (6,12,24 , 72 h) in each group.At 45 min after the left renal artery occlusion on the basis of the right renal resection,we restored perfusion in modeling of ischemia-reperfusion injury.To determine serum creatinine ( Scr) and to observe renal histological and ultrastructural changes.Results After ischemiareperfusion, the level of serum creatinine (Scr) was increased significantly,the morphology and ultrastructure of renal tissue were damaged significantly, which indicating that the construction of animal model was successful.Conclusion Using the technique to construct renal ischemiareperfusion rat model is simple and practical.%目的 建立一种简单实用的大鼠肾缺血再灌注损伤模型.方法 48只雄性SD大鼠随机分成2组:对照组(C组)、缺血再灌注组(Ir组),每组各4个时相(6、12、24、72 h).采用切除右肾,夹闭左肾动脉45 min后恢复灌流建立缺血再灌注损伤模型.检测血清肌酐(Scr)水平,观察肾组织病理学改变及超微结构变化.结果 缺血再灌注后,Scr水平显著升高,肾组织形态学和超微结构出现明显的损伤和破坏,表明动物模型建立成功.结论 该方法 建立大鼠肾缺血再灌注损伤模型简单实用.

  6. Exogenous alpha-1-acid glycoprotein protects against renal ischemia-reperfusion injury by inhibition of inflammation and apoptosis

    NARCIS (Netherlands)

    de Vries, B; Walter, SJ; Wolfs, TGAM; Hochepied, T; Rabina, J; Heeringa, P; Parkkinen, J; Libert, C; Buurman, WA

    2004-01-01

    Background. Although ischemia-reperfusion (I/R) injury represents a major problem in posttransplant organ failure, effective treatment is not available. The acute phase protein a-l-acid glycoprotein (AGP) has been shown to be protective against experimental I/R injury. The effects of AGP are thought

  7. Oxidative Stress and Lung Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Renata Salatti Ferrari

    2015-01-01

    Full Text Available Ischemia-reperfusion (IR injury is directly related to the formation of reactive oxygen species (ROS, endothelial cell injury, increased vascular permeability, and the activation of neutrophils and platelets, cytokines, and the complement system. Several studies have confirmed the destructiveness of the toxic oxygen metabolites produced and their role in the pathophysiology of different processes, such as oxygen poisoning, inflammation, and ischemic injury. Due to the different degrees of tissue damage resulting from the process of ischemia and subsequent reperfusion, several studies in animal models have focused on the prevention of IR injury and methods of lung protection. Lung IR injury has clinical relevance in the setting of lung transplantation and cardiopulmonary bypass, for which the consequences of IR injury may be devastating in critically ill patients.

  8. Effect of anisodine on acute forebrain ischemia-reperfusion damage in rats%樟柳碱对大鼠脑缺血再灌注损伤的影响

    Institute of Scientific and Technical Information of China (English)

    徐伟; 邓亦峰

    1996-01-01

    To study the protective effect of anisodine (Ani) on acute forebrain ischemia-reperfusion injury in rats. METHODS: Both vertebral arteries were occluded by electrocautery. Severe, but transient bilateral cerebral ischemia was produced by clamping both common carotid arteries in rats. Atomic absorption spectrophotometric and spectrophotometric methods were used to determine the contents of calcium and extravasated Evans blue (EB), respectively, remained in forebrain at 60-min recirculation after 30-min ischemia. RESULTS: At 60-min recirculation, the brain calcium contents were increased from 112 ± 6 μg/g brain dry weight in control (sham operation) group to 165 ± 7μg/g brain dry weight with marked increase of EB extravasation.and extravasated EB contents. CONCLUSION:Ani prevented the brain from ischemia insults through reducing intracellular calcium accumulation resulted from ischemia and reperfusion.%研究樟柳碱对大鼠急性脑缺血及再灌注损伤的影响.方法:电灼闭塞锥动脉并夹闭颈动脉,使大鼠前脑缺血30 min,放开双侧颈总动脉重灌60 min,并在重灌40 min时iv 2%伊文思蓝0.2 mL.分别用原子吸收分光光度法,分光光度法测定前脑钙含量和伊文思蓝含量.结果:缺血重灌后,大鼠脑钙含量由对照的112±6μg/g干重脑增加至165±7μg/g干重脑,伊文思蓝含量由对照的3.3±0.3μg/g湿重脑增加至6.7±0.5μg/g湿重脑,樟柳碱,东莨菪碱可使异常增高的脑钙含量以及伊文思蓝含量明显降低.结论:樟柳碱和东莨菪碱通过降低缺血及重灌引起的脑积累,减轻脑损伤改善脑功能.

  9. Effect of IL-13 on expression of IL-6 in acute renal ischemia/reperfusion injury in rats%IL-13对大鼠急性肾缺血再灌注时IL-6表达的影响

    Institute of Scientific and Technical Information of China (English)

    冯振伟; 江黎明; 陈孝文; 杨展; 吴平; 赵家明; 何惠娟

    2012-01-01

    Objective It is to observe the effects of IL - 13 on expression of IL -6 in acute renal ischemia/reperfusion injury in rats. Methods Thirty-seven male Wistar rats were randomly divided into 5 groups: sham group, I/R group, C group, T - S group and T - L group. Models of acute renal ischemic/reperfusion injury were established by blocking up kidneys blood flow in both side for 45 min and reperfusion for 24h in the rats. Rm - IL - 13 was injected into the renal arteries through the abdominal aorta in T - S group and T - L group( T - S 0. 5 μg/kg body weight, T - L 1. 5 μg/kg body weight ),normal saline instead of rm - IL -13 was injected into the renal arteries through the abdominal aorta in control group. The serum level of IL -6 and the renal expression of IL - 6 were determined in each group at 24 h post-ischemia. In addition, BUN, Cr and renal histology were also measured. Results The serum level of IL - 6 gene expression and protein production of IL - 6 in kidney decreased markedly in T - L group. Renal function and histology were significantly improved in T - L group, renal injury scores decreased significantly too. A positive correlation was found between the serum level of IL - 6, gene expression IL - 6 in kidney and BUN, SCr. Conclusion IL - 13 can inhibit the expression of IL - 6 and improve function and histology of kidney in rats with acute renal ischemia/reperfusion injury.%目的 观察白细胞介素13(IL-13)对急性缺血再灌注肾损伤大鼠IL-6表达的影响.方法 将Wistar雄性大鼠37只随机分为假手术组、I/R组、C组、T-S组和T-L组.阻断大鼠双侧肾脏血流45min,再灌注24h建立急性肾缺血再灌注模型;T-S组和T-L组于阻断血流后分别从双侧肾动脉开口注射入鼠重组白细胞介素13 0.5μg/kg和1.5μg/kg;C组以生理盐水代替.检测各组大鼠IL-6血清水平和肾脏表达情况以及肾功能和肾脏病理变化.结果 T-L组肾脏IL-6基因和蛋白表达明显减少,IL-6血清水平也

  10. Protective effects of icariin on neurons injured by cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    LI Li; ZHOU Qi-xin; SHI Jing-shan

    2005-01-01

    Background It is very important to search for novel anti-ischemia/reperfusion neuroprotective drugs for prevention or treatment of cerebrovascular diseases. Icariin, the major active component of traditional Chinese herb Yinyanghuo, may have a beneficial role for neurons in cerebral ischemia/reperfusion caused by accident. However, it was not clear yet. In this study, we observed the protective effects of icariin on neurons injured by ischemia/reperfusion in vitro and in vivo and investigated its protective mechanism.Methods Cerebral cortical neurons of Wistar rats in primary culture were studied during the different periods of oxygen-glucose deprivation and reperfusion with oxygen and glucose. Cell viability was determined by methyl thiazoleterazolium (MTT) assay. The activity of lactate dehydrogenase (LDH) leaked from neurons, cell apoptosis and the concentration of intracellular free calcium were measured respectively. On the other hand, the mice model of transient cerebral ischemia/reperfusion was made by bilateral occlusion of common carotid arteries and ischemic hypotension/reperfusion. The mice were divided into several groups at random: sham operated group, model group and icariin preventive treatment group. The changes of mice behavioral, activities of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were measured, respectively. Results Treatment with icariin (final concentration 0.25, 0.5, and 1 mg/L) during ischemia/reperfusion-mimetic incubation in vitro concentration-dependently attenuated neuronal damage with characteristics of increasing injured neuronal absorbance of MTT, decreasing LDH release, decreasing cell apoptosis, and blunting elevation of intracellular calcium concentration. And in vivo the learning and memory abilities significantly decreased,activities of SOD were diminished and MDA level increased obviously in model group,compared with that in sham operated group. But pre-treatment of model mice with icariin (10, 30

  11. Carnosic acid nanoparticles suppress liver ischemia/reperfusion injury by inhibition of ROS, Caspases and NF-κB signaling pathway in mice.

    Science.gov (United States)

    Li, Hui; Sun, Jian-Jun; Chen, Guo-Yong; Wang, Wei-Wei; Xie, Zhan-Tao; Tang, Gao-Feng; Wei, Si-Dong

    2016-08-01

    Living donor liver transplantation (LDLT) requires ischemia/reperfusion (I/R), which can lead to early graft injury. However, the detailed molecular mechanism of I/R injury remains unclear. Carnosic acid, as a phenolic diterpene with function of anti-inflammation, anti-cancer, anti-bacterial, anti-diabetic, as well as neuroprotective properties, is produced by many species from Lamiaceae family. Nanoparticulate drug delivery systems have been known to better the bioavailability of drugs on intranasal administration compared with only drug solutions. Administration of carnosic acid nanoparticles was thought to be sufficient to lead to considerable inhibition of liver injury progression induced by ischemia/reperfusion. In our study, liver ischemia/reperfusion injury was established successfully with C57BL/6 animal model. 10 and 20mg/kg carnosic acid nanoparticles were injected to mice for five days prior to ischemia. After liver ischemia/reperfusion, the levels of serum AST, ALT and APL were increased, which was attenuated by pre-treatment with carnosic acid nanoparticles. In addition, carnosic acid nanoparticles inhibited ROS production via its related signals regulation. And carnosic acid nanoparticles also suppressed the ischemia/reperfusion-induced up-regulation in the pro-apoptotic protein and mRNA levels of Bax, Cyto-c, Apaf-1 and Caspase-9/3 while increased ischemia/reperfusion-induced decrease of anti-apoptotic factor of Bcl-2. Further, ischemia/reperfusion-induced inflammation was also inhibited for carnosic acid nanoparticles administration via inactivating NF-κB signaling pathway, leading to down-regulation of pro-inflammatory cytokines releasing. In conclusion, our study suggested that carnosic acid nanoparticles protected against liver ischemia/reperfusion injury via its role of anti-oxidative, anti-apoptotic and anti-inflammatory bioactivity.

  12. The Effects of Two Anesthetics, Propofol and Sevoflurane, on Liver Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Zhijie Xu

    2016-04-01

    Full Text Available Background: Propofol and sevoflurane are widely used in clinical anesthesia, and both have been reported to exert a protective effect in organ ischemia/reperfusion (IR. This study aims to investigate and compare the effects of propofol and sevoflurane on liver ischemia/reperfusion and the precise molecular mechanism. Methods and Materials: Rats were randomized into four groups: the sham group, I/R group, propofol treatment group (infused with 1% propofol at 500 µg· kg-1· min-1, and sevoflurane treatment group (infused with 3% (2 L/min sevoflurane. The liver ischemia/reperfusion model was used to evaluate the hepatoprotective effect on ischemic injury. Liver enzyme leakage, liver cytokines and histopathological examination were used to evaluate the extent of hepatic ischemia/reperfusion injury. Oxidative stress was investigated by evaluating the levels of Malondialdehyde(MDA, Superoxide Dismutase(SOD and NO. The terminal dexynucleotidyl transferase(TdT-mediated dUTP nick end labeling (TUNEL assay and western blot were applied to detect apoptosis in the ischemic liver tissue and its mechanism. Results: Both propofol and sevoflurane attenuated the extent of hepatic ischemia/reperfusion injury which is evident from the hisopathological studies and alterations in liver enzymes such as AST and LDH by inhibiting Nuclear factor kappa B (NFκB activation and subsequent alterations in inflammatory cytokines interleukin-1(IL-1, interleukin-6(IL-6, tumor necrosis factor-alpha (TNF-a and increased IL10 release. Propofol exhibited a similar protective effect and a lower IL-1 release, while sevoflurane decreased TNF-a leakage more significantly. Meanwhile, oxidative stress was attenuated by reduced MDA and NO and elevated SOD release. The expression of antiapoptotic protein Bcl-2 and Bcl-xl were enhanced while that of apoptotic protein Bax and Bak were reduced by both propofol and sevoflurane to regulate hepatic apoptosis. In addition, propofol

  13. Extracellular BCL2 proteins are danger-associated molecular patterns that reduce tissue damage in murine models of ischemia-reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Akiko Iwata

    Full Text Available BACKGROUND: Ischemia-reperfusion (I/R injury contributes to organ dysfunction in a variety of clinical disorders, including myocardial infarction, stroke, organ transplantation, and hemorrhagic shock. Recent investigations have demonstrated that apoptosis as an important mechanism of cell death leading to organ dysfunction following I/R. Intracellular danger-associated molecular patterns (DAMPs released during cell death can activate cytoprotective responses by engaging receptors of the innate immune system. METHODOLOGY/PRINCIPAL FINDINGS: Ischemia was induced in the mouse hind limb by tourniquet or in the heart by coronary artery ligation. Reperfusion injury of skeletal or cardiac muscle was markedly reduced by intraperitoneal or subcutaneous injection of recombinant human (rhBCL2 protein or rhBCL2-related protein A1 (BCL2A1 (50 ng/g given prior to ischemia or at the time of reperfusion. The cytoprotective activity of extracellular rhBCL2 or rhBCL2A1 protein was mapped to the BH4 domain, as treatment with a mutant BCL2 protein lacking the BH4 domain was not protective, whereas peptides derived from the BH4 domain of BCL2 or the BH4-like domain of BCL2A1 were. Protection by extracellular rhBCL2 or rhBCL2A1 was associated with a reduction in apoptosis in skeletal and cardiac muscle following I/R, concomitant with increased expression of endogenous mouse BCL2 (mBCL2 protein. Notably, treatment with rhBCL2A1 protein did not protect mice deficient in toll-like receptor-2 (TLR2 or the adaptor protein, myeloid differentiation factor-88 (MyD88. CONCLUSIONS/SIGNIFICANCE: Treatment with cytokine-like doses of rhBCL2 or rhBCL2A1 protein or BH4-domain peptides reduces apoptosis and tissue injury following I/R by a TLR2-MyD88-dependent mechanism. These findings establish a novel extracellular cytoprotective activity of BCL2 BH4-domain proteins as potent cytoprotective DAMPs.

  14. Myocardial ischemia/reperfusion impairs neurogenesis and hippocampal-dependent learning and memory.

    Science.gov (United States)

    Evonuk, Kirsten S; Prabhu, Sumanth D; Young, Martin E; DeSilva, Tara M

    2017-03-01

    The incidence of cognitive impairment in cardiovascular disease (CVD) patients has increased, adversely impacting quality of life and imposing a significant economic burden. Brain imaging of CVD patients has detected changes in the hippocampus, a brain region critical for normal learning and memory. However, it is not clear whether adverse cardiac events or other associated co-morbidities impair cognition. Here, using a murine model of acute myocardial ischemia/reperfusion (I/R), where the coronary artery was occluded for 30min followed by reperfusion, we tested the hypothesis that acute myocardial infarction triggers impairment in cognitive function. Two months following cardiac I/R, behavioral assessments specific for hippocampal cognitive function were performed. Mice subjected to cardiac I/R performed worse in the fear-conditioning paradigm as well as the object location memory behavioral test compared to sham-operated mice. Reactive gliosis was apparent in the hippocampal subregions CA1, CA3, and dentate gyrus 72h post-cardiac I/R as compared with sham, which was sustained two months post-cardiac I/R. Consistent with the inflammatory response, the abundance of doublecortin positive newborn neurons was decreased in the dentate gyrus 72h and 2months post-cardiac I/R as compared with sham. Therefore, we conclude that following acute myocardial infarction, rapid inflammatory responses negatively affect neurogenesis, which may underlie long-term changes in learning and memory.

  15. The Impact of Prophylactic Fasciotomy Following Porcine (Sus scrofa) Hind Limb Ischemia/Reperfusion Injury

    Science.gov (United States)

    2012-03-23

    ANSI Std. Z39.18 The Impact of Prophylactic Fasciotomy Following Porcine (Sus scrofa ) Hind Limb Ischemia/reperfusion Injury CAPT Thomas J...porcine model of hind limb ischemia. Method: Swine (Sus Scrofa ; 76 +/-6kg) were randomly assigned to no fasciotomy or prophylactic fasciotomy after...of ischemic intervals on neuromuscular recovery in a porcine (Sus scrofa ) survival model of extremity vascular injury. J Vasc Surg. 2011 Jan;53(1):165

  16. Mechanism of Total Polyphenols Extracted from Toona sinensis Roem on Acute Inflammation during Myocardial Ischemia-reperfusion in Rats%基于炎症反应的香椿子总多酚抗大鼠心肌缺血再灌注损伤的机制研究

    Institute of Scientific and Technical Information of China (English)

    李红月; 陈超

    2012-01-01

    目的:观察香椿子总多酚对大鼠心肌缺血再灌注急性炎症的影响.方法:50只SD大鼠随机分成假手术组(冠脉下穿线不结扎+0.5%羧甲基纤维素钠)、模型组(冠脉结扎+0.5%羧甲基纤维素钠)、香椿子总多酚低剂量(XD,50 mg· kg-1+冠脉结扎)、中剂量(XZ,100 mg·kg-1+冠脉结扎)、高剂量(XG,200 mg· kg-1+冠脉结扎)组,各组均ig给药.采用左冠状动脉前降支结扎30 min再灌120 min的方法复制大鼠心肌缺血再灌注损伤模型.以ST抬高作为结扎成功的标志,以ST段逐渐回落、梗死性Q波出现作为再灌注成功的标志.再灌结束后行腹主动脉取血,分离血清,测定血清中白介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)含量.取左心室缺血区组织10 mg用RT-PCR测定核因子kB (NF-kB)p65 mRNA的表达水平,其余心肌组织做病理切片,并在光镜下观察左心室心肌组织的形态学变化.结果:模型组大鼠血清IL-6含量为(638.88±188.94) ng·L-1,XD,XZ,XG组与模型组相比,血清IL-6含量显著下降,分别为(491.58±142.59),(306.85±80.60),(246.11 ±71.64) ng·L-1.模型组大鼠血清TNF-α含量为(216.23 ±58.67) ng·L-1,XD,XZ,XG组大鼠血清TNF-α水平与之相比显著降低,分别为(148.24 -±36.30),(157.62 ±52.06),(144.10 ±36.64) ng·L-1.模型组大鼠心肌组织中NF-kBp65/β-actin为0.61 ±0.05,香椿子总多酚给药组大鼠NF-kB p65/β-actin与之相比显著降低,分别为0.53 ±0.08,0.45 ±0.13,0.38 ±0.11.香椿子总多酚组与模型组相比,大鼠心肌细胞的形态学损伤较轻.结论:香椿子总多酚能够减轻大鼠心肌缺血再灌注急性炎症,对其产生一定的保护作用.%Objective: To investigate effects of total polyphenols extracted from Toona sinensis Roem on acute inflammation in injury induced by myocardial ischemia-reperfusion in rats. Method: Fifty SD rats were randomly divided into 5 groups: sham operation group, model group and total polyphenols extracted from T

  17. Propofol inhibits inflammation and lipid peroxidation following cerebral ischemia/ reperfusion in rabbits

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Wei; Xing Wan; Bo Zhao; Jiabao Hou; Min Liu; Bangchang Cheng

    2012-01-01

    The present study established a rabbit model of global cerebral ischemia using the ‘six-vessel' method, which was reperfused after 30 minutes of ischemia. Rabbits received intravenous injection of propofol at 5 mg/kg prior to ischemia and 20 mg/kg per hour after ischemia until samples were prepared. Results revealed that propofol inhibited serum interleukin-8, endothelin-1 and malondialdehyde increases and promoted plasma superoxide dismutase activity after cerebral ischemia/reperfusion. In addition, cerebral cortex edema was attenuated with little neuronal nuclear degeneration and pyknosis with propofol treatment. The cross-sectional area of neuronal nuclei was, however, increased following propofol treatment. These findings suggested that propofol could improve anti-oxidant activity and inhibit synthesis of inflammatory factors to exert a protective effect on cerebral ischemia/reperfusion injury.

  18. Protection of Puerarin on Oxidative Stress Induced by Acute Myocardial Ischemia-Reperfusion Injury in Rats in Cardiopulmonary Bypass%葛根素对大鼠体外循环后心肌缺血再灌注损伤的保护作用及抗氧化应激机制的探讨

    Institute of Scientific and Technical Information of China (English)

    巩红岩; 秦元旭; 王更富; 王庆志

    2012-01-01

    目的:探讨葛根素对大鼠体外循环后心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MIRI)的保护作用及抗氧化应激机制.方法:取健康雄性SD大鼠75只,随机分为5组:即假手术组(给予等体积的生理盐水)、MIRI模型组(给予等体积的生理盐水)、葛根素低、中、高剂量组(2,5,10 mg·kg-13个剂量).于再灌注开始时在储血槽内加入稀释葛根素10mL.在全麻手术下制造大鼠体外循环模型后,随即阻断大鼠升主动脉造成心肌缺血30 min然后开放升主动脉后再灌注180 min造成大鼠心肌缺血再灌注损伤模型(灌注24 h,用于测定心肌梗死面积).实验组和对照组分别给予葛根素和生理盐水.实验完成后留取大鼠心脏标本,观察大鼠心肌缺血区的心肌细胞凋亡情况;收集血清测定其抗氧化应激的指标:超氧化物歧化酶(SOD),丙二醛(MDA),谷胱甘肽(GSH),谷胱甘肽过氧化物酶(GSH-Px).结果:与模型组相比,葛根素的应用减少了MIRI大鼠的心肌细胞凋亡、心梗面积和血清中丙二醛的含量,增加了血清中超氧化物歧化酶、谷胱甘肽过氧化物酶的活性和谷胱甘肽的含量,并且随着剂量的增加保护效果尤为明显.结论:葛根素对MIRI大鼠具有抗氧化应激的作用,它能够剂量依赖性的减少心肌细胞凋亡,最终减少心肌梗死面积.%Objective: To investigate the protective mechanism of puerarin on acute myocardial ischemia -reperfusion injury( MIRI) in rats, and to explain the antioxidative mechanism involved. Method: Rat MIRI model was induced by ischemia for 30 min and reperfusion for 180 min. At the end of the 3 h reperfusion period (or 24 h for infarct. Size ), myocardial infarct size, myocardial apoptosis and the activity of antioxidative enzymes were measured. Result: Puerarin reduced infarct size, myocardial apoptosisand the serum level of malondialdehyde, increased the activity of superoxide dismutase and glutathione

  19. Dose-dependent effects of procyanidin on nerve growth factor expression following cerebral ischemia/ reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Feng Li; Hai Xie; Ying Gao; Tongxia Zhan

    2008-01-01

    BACKGROUND: Recently, grape seed procyanidin (GSP) has been shown to be exhibit antioxidant effects, effectively reducing ischemia/reperfusion injury and inhibiting brain cell apoptosis.OBJECTIVE: To study the effects of GSP on nerve growth factor (NGF) expression and neurological function following cerebral ischemia/reperfusion injury in rats.DESIGN: Randomized controlled study based on SD rats.SETTING: Weifang Municipal People's Hospital. MATERIALS: Forty-eight healthy adult SD rats weighing 280-330 g and irrespective of gender were provided by the Experimental Animal Center of Shandong University. GSP derived from grape seed was a new high-effective antioxidant provided by Tianjin Jianfeng Natural Product Researching Company (batch number: 20060107). Rabbit-anti-rat NGF monoclonal antibody was provided by Beijing Zhongshan Biotechnology Co., Ltd., and SABC immunohistochemical staining kit by Wuhan Boster Bioengineering Co., Ltd. METHODS: The present study was performed in the Functional Laboratory of Weifang Medical College from April 2006 to January 2007. Forty-eight SD rats were randomly divided into the sham operation group, ischemia/reperfusion group, high-dose GSP (40 mg/kg) group, or low-dose GSP (10 mg/kg) group (n = 12 per group). Ischemia/reperfusion injury was established using the threading embolism method of the middle cerebral artery. Rats in the ischemia/reperfusion model group were given saline injection (2 mL/kg i.p.) once daily for seven days pre-ischemia/reperfusion, and once more at 15 minutes before reperfusion. Rats in the high-dose and low-dose GSP groups were injected with GSP (20 or 5 mg/mL i.p., respectively, 2 mL/kg) with the same regime as the ischemia/reperfusion model group. The surgical procedures in the sham operation group were as the same as those in the ischemia/reperfusion model group, but the thread was approximately 10 mm long, thus, the middle cerebral artery was not blocked. MAIN OUTCOME MEASURES: NGF expression in the

  20. The protective effect of diosmin on hepatic ischemia reperfusion injury: an experimental study

    Science.gov (United States)

    Tanrikulu, Yusuf; Şahin, Mefaret; Kismet, Kemal; Kilicoglu, Sibel Serin; Devrim, Erdinc; Tanrikulu, Ceren Sen; Erdemli, Esra; Erel, Serap; Bayraktar, Kenan; Akkus, Mehmet Ali

    2013-01-01

    Liver ischemia reperfusion injury (IRI) is an important pathologic process leading to bodily systemic effects and liver injury. Our study aimed to investigate the protective effects of diosmin, a phlebotrophic drug with antioxidant and anti-inflammatory effects, in a liver IRI model. Forty rats were divided into 4 groups. Sham group, control group (ischemia-reperfusion), intraoperative treatment group, and preoperative treatment group. Ischemia reperfusion model was formed by clamping hepatic pedicle for a 60 minute of ischemia followed by liver reperfusion for another 90 minutes. Superoxide dismutase (SOD) and catalase (CAT) were measured as antioaxidant enzymes in the liver tissues, and malondialdehyde (MDA) as oxidative stress marker, xanthine oxidase (XO) as an oxidant enzyme and glutathione peroxidase (GSH-Px) as antioaxidant enzyme were measured in the liver tissues and the plasma samples. Hepatic function tests were lower in treatment groups than control group (p<0.001 for ALT and AST). Plasma XO and MDA levels were lower in treatment groups than control group, but plasma GSH-Px levels were higher (p<0.05 for all). Tissue MDA levels were lower in treatment groups than control group, but tissue GSH-Px, SOD, CAT and XO levels were higher (p<0.05 for MDA and p<0.001 for others). Samples in control group histopathologically showed morphologic abnormalities specific to ischemia reperfusion. It has been found that both preoperative and intraoperative diosmin treatment decreases cellular damage and protects cells from toxic effects in liver IRI. As a conclusion, diosmin may be used as a protective agent against IRI in elective and emergent liver surgical operations. PMID:24289756

  1. Effect and mechanism of salvianolic acid B on the myocardial ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Ling Xue; Zhen Wu; Xiao-Ping Ji; Xia-Qing Gao; Yan-Hua Guo

    2014-01-01

    Objective: To investigate the effect of salvianolic acid B on rats with myocardial ischemia-reperfusion injury. Methods: SD rats were randomly divided into five groups (n=10 in each group): A sham operation group, B ischemic reperfusion group model group, C low dose salvianolic acid B group, D median dose salvianolic acid B group, E high dose salvianolic acid B group. One hour after establishment of the myocardial ischemia-reperfusion model, the concentration and the apoptotic index of the plasma level of myocardial enzymes (CTnⅠ, CK-MB), SOD, MDA, NO, ET were measured. Heart tissues were obtained and micro-structural changes were observed. Results: Compared the model group, the plasma CTnⅠ, CK-MB, MDA and ET contents were significantly increased, NO, T-SOD contents were decreased in the treatment group (group C, D, and E) (P<0.05); compared with group E, the plasma CTnⅠ, CK-MB, MDA and ET levels were increased, the NO, T-SOD levels were decreased in groups C and D (P<0.05). Infarct size was significantly reduced, and the myocardial ultrastructural changes were improved significantly in treatment group. Conclusions: Salvianolic acid B has a significant protective effect on myocardial ischemia-reperfusion injury. It can alleviate oxidative stress, reduce calcium overload, improve endothelial function and so on.

  2. Role of Mitochondria in Neuron Apoptosis during Ischemia-Reperfusion Injury

    Institute of Scientific and Technical Information of China (English)

    段秋红; 王西明; 王忠强; 卢涛; 韩义香; 何善述

    2004-01-01

    To investigate the role of mitochondria in neuronal apoptosis, ischemia-reperfusion mediated neuronal cell injury model was established by depriving of glucose, serum and oxygen in media.DNA fragmentation, cell viability, cytochrome C releasing, caspase3 activity and mitochondrial transmembrane potential were observed after N2a cells suffered the insults. The results showed that N2a cells in ischemic territory exhibited survival damage, classical cell apoptosis change, DNA ladder and activation of caspase3. Apoptosis-related alterations in mitochondrial functions, including release of cytochrome C and depression of mitochondrial transmembrane potential (△ψm)were testified in N2a cells after mimic ischemia-reperfusion. Moreover, activation of caspase3 occurred following the release of cytochrome C. However, the inhibitor of caspase3, Ac-DEVDinhibitor of mitochondria permeability transition pore only partly inhibited caspase3 activity and reduced DNA damage. Interestingly, treatment of Z-IETD-FMK, an inhibitor of caspase8 could comthat there were caspase3 dependent and independent cellular apoptosis pathways in N2a cells suffering ischemia-reperfusion insults. Mitochondria dysfunction may early trigger apoptosis and amplify apoptosis signal.

  3. Noscapine protects OLN-93 oligodendrocytes from ischemia-reperfusion damage: Calcium and nitric oxide involvement.

    Science.gov (United States)

    Nadjafi, S; Ebrahimi, S-A; Rahbar-Roshandel, N

    2015-12-01

    This study was carried out to evaluate the effects of noscapine, a benzylisoquinoline alkaloid from opium poppy, on oligodendrocyte during ischemia/reperfusion-induced excitotoxic injury. Changes in intracellular calcium levels due to chemical ischemia and nitric oxide (NO) production during ischemia/reperfusion were evaluated as the hallmarks of ischemia-derived excitotoxic event. OLN-93 cell line (a permanent immature rat oligodendrocyte) was used as a model of oligodendrocyte. 30- or 60-minute-oxygen-glucose deprivation/24 hours reperfusion were used to induce excitotoxicity. MTT (3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay was used to evaluate cell viability. Ratiometric fluorescence microscopy using Ca(2+)-sensitive indicator Fura-2/AM was utilized to assess intracellular calcium levels. NO production was evaluated by Griess method. Noscapine (4 μM) significantly attenuated intracellular Ca(2+) elevation (P noscapine significantly decreased NO production during a 30-minute oxygen-glucose deprivation/reperfusion (P noscapine (4 μM) on intracellular Ca(2+) was greater than ionotropic glutamate receptors antagonists. Noscapine is protective against ischemia/reperfusion-induced excitotoxic injury in OLN-93 oligodendrocyte. This protective effect seems to be related to attenuation of intracellular Ca(2+) overload and NO production.

  4. Rapamycin alleviates brain edema after focal cerebral ischemia reperfusion in rats.

    Science.gov (United States)

    Guo, Wei; Feng, Guoying; Miao, Yanying; Liu, Guixiang; Xu, Chunsheng

    2014-06-01

    Brain edema is a major consequence of cerebral ischemia reperfusion. However, few effective therapeutic options are available for retarding the brain edema progression after cerebral ischemia. Recently, rapamycin has been shown to produce neuroprotective effects in rats after cerebral ischemia reperfusion. Whether rapamycin could alleviate this brain edema injury is still unclear. In this study, the rat stroke model was induced by a 1-h left transient middle cerebral artery occlusion using an intraluminal filament, followed by 48 h of reperfusion. The effects of rapamycin (250 μg/kg body weight, intraperitoneal; i.p.) on brain edema progression were evaluated. The results showed that rapamycin treatment significantly reduced the infarct volume, the water content of the brain tissue and the Evans blue extravasation through the blood-brain barrier (BBB). Rapamycin treatment could improve histological appearance of the brain tissue, increased the capillary lumen space and maintain the integrity of BBB. Rapamycin also inhibited matrix metalloproteinase 9 (MMP9) and aquaporin 4 (AQP4) expression. These data imply that rapamycin could improve brain edema progression after reperfusion injury through maintaining BBB integrity and inhibiting MMP9 and AQP4 expression. The data of this study provide a new possible approach for improving brain edema after cerebral ischemia reperfusion by administration of rapamycin.

  5. Neuroprotective Effect of Ulinastatin on Spinal Cord Ischemia-Reperfusion Injury in Rabbits

    Directory of Open Access Journals (Sweden)

    Bingbing Liu

    2015-01-01

    Full Text Available Ulinastatin (UTI, a trypsin inhibitor, is isolated and purified from human urine and has been shown to exert protective effect on myocardial ischemia reperfusion injury in patients. The present study was aimed at investigating the effect of ulinastatin on neurologic functions after spinal cord ischemia reperfusion injury and the underlying mechanism. The spinal cord IR model was achieved by occluding the aorta just caudal to the left renal artery with a bulldog clamp. The drugs were administered immediately after the clamp was removed. The animals were terminated 48 hours after reperfusion. Neuronal function was evaluated with the Tarlov Scoring System. Spinal cord segments between L2 and L5 were harvested for pathological and biochemical analysis. Ulinastatin administration significantly improved postischemic neurologic function with concomitant reduction of apoptotic cell death. In addition, ulinastatin treatment increased SOD activity and decreased MDA content in the spinal cord tissue. Also, ulinastatin treatment suppressed the protein expressions of Bax and caspase-3 but enhanced Bcl-2 protein expression. These results suggest that ulinastatin significantly attenuates spinal cord ischemia-reperfusion injury and improves postischemic neuronal function and that this protection might be attributable to its antioxidant and antiapoptotic properties.

  6. Myeloid PTEN deficiency protects livers from ischemia reperfusion injury by facilitating M2 macrophage differentiation.

    Science.gov (United States)

    Yue, Shi; Rao, Jianhua; Zhu, Jianjun; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W; Lu, Ling; Wang, Xuehao; Zhai, Yuan

    2014-06-01

    Although the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in regulating cell proliferation is well established, its function in immune responses remains to be fully appreciated. In the current study, we analyzed myeloid-specific PTEN function in regulating tissue inflammatory immune response in a murine liver partial warm ischemia model. Myeloid-specific PTEN knockout (KO) resulted in liver protection from ischemia reperfusion injury (IRI) by deviating the local innate immune response against ischemia reperfusion toward the regulatory type: expression of proinflammatory genes was selectively decreased and anti-inflammatory IL-10 was simultaneously increased in ischemia reperfusion livers of PTEN KO mice compared with those of wild-type (WT) mice. PI3K inhibitor and IL-10-neutralizing Abs, but not exogenous LPS, recreated liver IRI in these KO mice. At the cellular level, Kupffer cells and peritoneal macrophages isolated from KO mice expressed higher levels of M2 markers and produced lower TNF-α and higher IL-10 in response to TLR ligands than did their WT counterparts. They had enhanced Stat3- and Stat6-signaling pathway activation, but diminished Stat1-signaling pathway activation, in response to TLR4 stimulation. Inactivation of Kupffer cells by gadolinium chloride enhanced proinflammatory immune activation and increased IRI in livers of myeloid PTEN KO mice. Thus, myeloid PTEN deficiency protects livers from IRI by facilitating M2 macrophage differentiation.

  7. Warm ischemia time-dependent variation in liver damage, inflammation, and function in hepatic ischemia/reperfusion injury

    NARCIS (Netherlands)

    Olthof, Pim B.; Golen, van Rowan F.; Meijer, Ben; Beek, van Adriaan A.; Bennink, Roelof J.; Verheij, Joanne; Gulik, van Thomas M.; Heger, Michal

    2017-01-01

    Background

    Hepatic ischemia/reperfusion (I/R) injury is characterized by hepatocellular damage, sterile inflammation, and compromised postoperative liver function. Generally used mouse I/R models are too severe and poorly reflect the clinical injury profile. The aim was to establish a mouse

  8. The study of protective effects and mechanisms of rofecoxib on focal cerebral ischemia- reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    YUJuan; ZHOUYu; QIULi-Ying; CHENBai-Ling; CHENChong-Hong

    2004-01-01

    AIM : To study the protective effects and the mechanisms of rofecoxib as a specific type 2 cyclooxygenase (COX- 2 inhibitor on focal cerebral ischemia reperfusion injury ( CIRI in rats. METHODS : The model of focal CIRI was induced by reversible middle cerebral artery occlusion ( MCAO with inserting a thread through internal carotid artery, 2 h occlusion followed

  9. Pretreatment with Danhong injection protects the brain against ischemia-reperfusion injury.

    Science.gov (United States)

    Wang, Shaoxia; Guo, Hong; Wang, Xumei; Chai, Lijuan; Hu, Limin; Zhao, Tao; Zhao, Buchang; Tan, Xiaoxu; Jia, Feifei

    2014-08-01

    Danhong injection (DHI), a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is widely used in China for treating acute ischemic stroke. In the present study, we explored the neuroprotective efficacy of DHI in a rat model of temporary middle cerebral artery occlusion, and evaluated the potential mechanisms underlying its effects. Pretreatment with DHI (0.9 and 1.8 mL/kg) resulted in a significantly smaller infarct volume and better neurological scores than pretreatment with saline. Furthermore, DHI significantly reduced the permeability of the blood-brain barrier, increased occludin protein expression and decreased neutrophil infiltration, as well as profoundly suppressing the upregulation of matrix metallopeptidase-9 expression seen in rats that had received vehicle. Matrix metallopeptidase-2 expression was not affected by ischemia or DHI. Moreover, DHI (1.8 mL/kg) administered 3 hours after the onset of ischemia also improved neurological scores and reduced infarct size. Our results indicate that the neuroprotective efficacy of DHI in a rat model of cerebral ischemia-reperfusion injury is mediated by a protective effect on the blood-brain barrier and the reversal of neutrophil infiltration.

  10. Propofol Prevents Renal Ischemia-Reperfusion Injury via Inhibiting the Oxidative Stress Pathways

    Directory of Open Access Journals (Sweden)

    Yingjie Li

    2015-08-01

    Full Text Available Background/Aims: Renal ischemia/reperfusion injury (IRI is a risk for acute renal failure and delayed graft function in renal transplantation and cardiac surgery. The purpose of this study is to determine whether propofol could attenuate renal IRI and explore related mechanism. Methods: Male rat right kidney was removed, left kidney was subjected to IRI. Propofol was intravenously injected into rats before ischemia. The kidney morphology and renal function were analyzed. The expression of Bax, Bcl-2, caspase-3, cl-caspase-3, GRP78, CHOP and caspase-12 were detected by Western blot analysis. Results: IR rats with propofol pretreatment had better renal function and less tubular apoptosis than untreated IR rats. Propofol pretreated IR rats had lower Bax/Bcl-2 ratio and less cleaved caspase-3. The protein expression levels of GRP78, CHOP and caspase-12 decreased significantly in propofol pretreated IR rats. In vitro cell model showed that propofol significantly increased the viability of NRK-52E cells that were subjected to hypoxia/reoxygenation (H/R in a dose-dependent manner. The effect of propofol on the expression regulation of Bax, Bcl-2, caspase-3, GRP78, CHOP was consistent in both in vitro and in vivo models. Conclusion: Experimental results suggest that propofol prevents renal IRI via inhibiting oxidative stress.

  11. Role of Nitric Oxide and Nitric Oxide Synthases in Ischemia-reperfusion Injury in Rat Organotypic Hippocampus Slice

    Institute of Scientific and Technical Information of China (English)

    MENG Xianfang; SHI Jing; LIU Xiaochun; ZHANG Jing; SUN Ning

    2005-01-01

    To investigate the effects of ischemia-reperfusion on the levels of nitric oxide and nitric oxide synthase isoforms (nNOS and iNOS), rat organotypic hippocampus slice were cultured in vitro and subjected to ischemia by oxygen glucose deprivation (OGD) for 30 min and then placed in the normal culture condition. The ischemia-reperfusion produced a time-dependent increase in nitrite levels in the culture medium. Reverse transcriptional-polymerase chain reaction showed augmented levels of mRNA for both nNOS and iNOS when compared with control at 12 h and remained increase at 36 h after OGD (P<0.05). The protein levels of both nitric oxide synthase isoforms increased significantly as determined by Western Blot. OGD also caused neurotoxicity in this model as revealed by the elevated lactate dehydrogenase (LDH) efflux into the incubation solution. The results suggest that organotypic hippocampus slice is a useful model in studying ischemia-reperfusion brain injury. NO and NOS may play a critical role in the ischemia-reperfusion brain damage in vitro.

  12. Establishment of a rat model of general ischemia-reperfusion injury%大鼠全身性缺血-再灌注损伤模型的建立

    Institute of Scientific and Technical Information of China (English)

    樊凤艳; 王洪波; 周菁; 魏少平

    2011-01-01

    Objective: To establish a rat model of general ischemia-reperfusion injury. Methords: Thirty Wistar rats achieved ischemia by hemorrhage and achieved reperfusion iniury by infusion of the bled blood. 1 hour after hemorrhage the total bled blood was reinfused into the animals and the rats were killed 3 houes later. Mean arterial pressure(MAP), heart rates, anus temperature and electrocardiogram (ECG) were monitored all the time. Blood samples were taken before hemorrhage and after 3 hours of inspection were analyzed for serum aspartate aminotransferase ( AST), alanin aminotransferase ( ALT), lactate dehydrogenase (LDH). Heart, kidney, brain and lung samples were taken for histopathological analysis. Results: The results showed that data of MAP, heart rates,anus temperature were normal distribution. Compared with those before hemorrhage the AST, ALT, LDH increased significantly after 3 hours of reperfusion iniury. The changes of ECG after ischemia and reperfusion accorded with ischemia and reperfusion injury. Histopathological changes of heart, kidney, brain and lung after 3 hours of reperfusion accorded with reperfusion injury. Conclusion: A rat model of general ischemia-reperfusion injury was successfully established.%目的:建立大鼠全身性缺血-再灌注损伤模型.方法:30只大鼠快速放血至平均动脉压(MAP)40 mmHg,慢速放血维持20 min,室温放置1 h,全部失血回输.3 h后将大鼠处死,期间监测大鼠MAP、心率、肛温、心电图,并检测大鼠放血前及再灌注后3 h血浆天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、乳酸脱氢酶(LDH)值.取心、肾、脑、肺标本作组织病理检测.结果:放血结束时及再灌注前MAP、心率、肛温符合正态分布.再灌注后3 h血浆AST、ALT、LDH活性均显著高于放血前(P<0.01).大鼠失血后心电图发生缺血样改变.再灌注后3 h心电图显示损伤加重.心、肾、脑、肺组织均显示明显再灌注损伤样病理学改变.结论:成

  13. 大鼠心肌缺血-再灌注模型的心电图变化%Electrocardiogram changes on myocardial ischemia-reperfusion model in rats

    Institute of Scientific and Technical Information of China (English)

    温剑艺; 谭宁; 杨大浩

    2011-01-01

    Objectives To explore the electrocardiogram changes of myocardial ischemia and reperfusion in rats. Methods Twenty three male rats were randomly divided into two groups: ischemia-reperfusion injury group (I/R group) and sham group. Surgery of left coronary artery ligation was carried on in I/R group, while only left coronary artery anatomy was performed in sham group. Post ligation for 35 min, reperfusion for 120 min were performed in I/R group. Heart infarct area was examined with tetrazolium chloride (TTC) staining. Changes of P wave,QRS complex,T wave, ST-segment, heart rates and the occurrence of arrhythmia were observed in electrocardiogram of lead Ⅱ. Results Three rats in I/R group died. There was no infarct area in sham group, while I/R group's infarct area was 45.31%±11.55%. Compared with sham group, R waves, P waves, T waves and ST-segment of I/R group rose during the occlusion of the left coronary artery. T waves and ST-segment descended when reperfused for 15 min, which was about 50%. Heart rates of I/R group declined during occlusion and resumed when reperfused. Ventricular arrhythmia appeared in I/R group, which occurred mainly after 5-10 min of the coronary artery occlusion and early reperfusion. Ventricular arrhythmia were mainly premature ventricular contractions, ventricular tachycardia, while occasional ventricular fibrillation and ventricular flutter were extremely seen. Conclusions ST-segment elevates, T wave amplitude increases within 15 min of myocardial ischemia, both of which could be considered as the sign of rat coronary artery ligation exactly. Within 15 min of reperfusion, ST-segment and T wave drops more than 50% rapidly. Besides, heart rate declines after the ligation of coronary artery.%目的 研究大鼠心肌缺血再灌注模型的心电图变化.方法 将23只雄性大鼠按电脑随机数字表法分为假手术组及缺血再灌注损伤组.缺血再灌注损伤组结扎左前降支35 min,再灌注120 min;而假手术组

  14. DAP12 expression in lung macrophages mediates ischemia/reperfusion injury by promoting neutrophil extravasation.

    Science.gov (United States)

    Spahn, Jessica H; Li, Wenjun; Bribriesco, Alejandro C; Liu, Jie; Shen, Hua; Ibricevic, Aida; Pan, Jie-Hong; Zinselmeyer, Bernd H; Brody, Steven L; Goldstein, Daniel R; Krupnick, Alexander S; Gelman, Andrew E; Miller, Mark J; Kreisel, Daniel

    2015-04-15

    Neutrophils are critical mediators of innate immune responses and contribute to tissue injury. However, immune pathways that regulate neutrophil recruitment to injured tissues during noninfectious inflammation remain poorly understood. DAP12 is a cell membrane-associated protein that is expressed in myeloid cells and can either augment or dampen innate inflammatory responses during infections. To elucidate the role of DAP12 in pulmonary ischemia/reperfusion injury (IRI), we took advantage of a clinically relevant mouse model of transplant-mediated lung IRI. This technique allowed us to dissect the importance of DAP12 in tissue-resident cells and those that infiltrate injured tissue from the periphery during noninfectious inflammation. Macrophages in both mouse and human lungs that have been subjected to cold ischemic storage express DAP12. We found that donor, but not recipient, deficiency in DAP12 protected against pulmonary IRI. Analysis of the immune response showed that DAP12 promotes the survival of tissue-resident alveolar macrophages and contributes to local production of neutrophil chemoattractants. Intravital imaging demonstrated a transendothelial migration defect into DAP12-deficient lungs, which can be rescued by local administration of the neutrophil chemokine CXCL2. We have uncovered a previously unrecognized role for DAP12 expression in tissue-resident alveolar macrophages in mediating acute noninfectious tissue injury through regulation of neutrophil trafficking.

  15. The anti-coagulants asis or apc do not protect against renal ischemia/ reperfusion injury

    Directory of Open Access Journals (Sweden)

    Sarah T.B.G. Loubele

    2014-06-01

    Full Text Available Renal ischemia/reperfusion (I/R injury is the main cause of acute renal failure. The severity of injury is determined by endothelial damage as well as inflammatory and apoptotic processes. The anticoagulants active site inhibited factor VIIa (ASIS and activated protein C (APC are besides their anticoagulant function also known for their cytoprotective properties. In this study the effect of ASIS and APC was assessed on renal I/R injury and this in relation to inflammation and apoptosis. Our results showed no effect of ASIS or APC on renal injury as determined by histopathological scoring as well as by blood urea nitrogen (BUN and creatinine levels. Furthermore, no effect on fibrin staining was detected but ASIS did reduce tissue factor activity levels after a 2-hr reperfusion period. Neither ASIS nor APC administration influenced overall inflammation markers, although some inflammatory effects of ASIS on interleukin (IL-1β and tumor necrosis factor (TNF-α were detectable after 2 hr of reperfusion. Finally, neither APC nor ASIS had an influence on cell signaling pathways or on the number of apoptotic cells within the kidneys. From this study we can conclude that the anticoagulants ASIS and APC do not have protective effects in renal I/R injury in the experimental setup as used in this study which is in contrast to the protective effects of these anticoagulants in other models of I/R.

  16. Protective effects of erdosteine and vitamins C and E combination on ischemia-reperfusion-induced lung oxidative stress and plasma copper and zinc levels in a rat hind limb model.

    Science.gov (United States)

    Sirmali, Mehmet; Uz, Efkan; Sirmali, Rana; Kilbaş, Aynur; Yilmaz, H Ramazan; Altuntaş, Irfan; Naziroğlu, Mustafa; Delibaş, Namik; Vural, Hüseyin

    2007-07-01

    The aim of this study was to investigate the protective effects of erdosteine and vitamins C and E (VCE) on the lungs after performing hind limb ischemia-reperfusion (I/R) by assessing oxidative stress, plasma copper (Cu), and zinc (Zn) analysis. The animals were divided randomly into four groups as nine rats each as follows: control, I/R, I/R plus erdosteine, and I/R plus VCE combination. I/R period for 60 min was performed on the both hind limbs of all the rats in the groups of I/R, erdosteine with I/R, VCE with I/R allowing 120 min of reperfusion. The animals received orally erdosteine one time in a day and 3 days before I/R in the erdosteine group. In the VCE group, the animals VCE combination received one time in a day and 3 days before I/R, although placebo was given to control and I/R group animals. Lung lipid peroxidation (malondialdehyde [MDA]) level, superoxide dismutase (SOD), and catalase activities were increased, although lung glutathione (GSH) and plasma Zn levels decreased in I/R group in lung tissue compared with the control group. Serum MDA level, creatine kinase, and lactate dehydrogenase activities were increased in I/R group compared with the control. Lung MDA and plasma Zn levels and lung SOD activity were decreased by erdosteine administration, whereas lung GSH levels after I/R increased. The plasma Zn levels and lung SOD activity were decreased by VCE administration, although the plasma Cu and lung GSH levels increased after I/R. In conclusion, erdosteine has an antioxidant role on the values in the rat model, and it has more protective affect than in VCE in attenuating I/R-induced lung injury in rats.

  17. MRI Dynamically Evaluates the Therapeutic Effect of Recombinant Human MANF on Ischemia/Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Xian-Yun Wang

    2016-09-01

    Full Text Available As an endoplasmic reticulum (ER stress-inducible protein, mesencephalic astrocyte-derived neurotrophic factor (MANF has been proven to protect dopaminergic neurons and nondopaminergic cells. Our previous studies had shown that MANF protected against ischemia/reperfusion injury. Here, we developed a magnetic resonance imaging (MRI technology to dynamically evaluate the therapeutic effects of MANF on ischemia/reperfusion injury. We established a rat focal ischemic model by using middle cerebral artery occlusion (MCAO. MRI was performed to investigate the dynamics of lesion formation. MANF protein was injected into the right lateral ventricle at 3 h after reperfusion following MCAO for 90 min, when the obvious lesion firstly appeared according to MRI investigation. T2-weighted imaging for evaluating the therapeutic effects of MANF protein was performed in ischemia/reperfusion injury rats on Days 1, 2, 3, 5, and 7 post-reperfusion combined with histology methods. The results indicated that the administration of MANF protein at the early stage after ischemia/reperfusion injury decreased the mortality, improved the neurological function, reduced the cerebral infarct volume, and alleviated the brain tissue injury. The findings collected from MRI are consistent with the morphological and pathological changes, which suggest that MRI is a useful technology for evaluating the therapeutic effects of drugs.

  18. Mechanistic overview of reactive species-induced degradation of the endothelial glycocalyx during hepatic ischemia/reperfusion injury.

    Science.gov (United States)

    van Golen, Rowan F; van Gulik, Thomas M; Heger, Michal

    2012-04-15

    Endothelial cells are covered by a delicate meshwork of glycoproteins known as the glycocalyx. Under normophysiological conditions the glycocalyx plays an active role in maintaining vascular homeostasis by deterring primary and secondary hemostasis and leukocyte adhesion and by regulating vascular permeability and tone. During (micro)vascular oxidative and nitrosative stress, which prevails in numerous metabolic (diabetes), vascular (atherosclerosis, hypertension), and surgical (ischemia/reperfusion injury, trauma) disease states, the glycocalyx is oxidatively and nitrosatively modified and degraded, which culminates in an exacerbation of the underlying pathology. Consequently, glycocalyx degradation due to oxidative/nitrosative stress has far-reaching clinical implications. In this review the molecular mechanisms of reactive oxygen and nitrogen species-induced destruction of the endothelial glycocalyx are addressed in the context of hepatic ischemia/reperfusion injury as a model disease state. Specifically, the review focuses on (i) the mechanisms of glycocalyx degradation during hepatic ischemia/reperfusion, (ii) the molecular and cellular players involved in the degradation process, and (iii) its implications for hepatic pathophysiology. These topics are projected against a background of liver anatomy, glycocalyx function and structure, and the biology/biochemistry and the sources/targets of reactive oxygen and nitrogen species. The majority of the glycocalyx-related mechanisms elucidated for hepatic ischemia/reperfusion are extrapolatable to the other aforementioned disease states.

  19. The Effects and Innovation of Rabbit Heart Ischemia-reperfusion Model in Vitro%家兔离体心脏缺血再灌注模型制作方法的改进及其效果

    Institute of Scientific and Technical Information of China (English)

    王伟; 王天仕; 谷艳芳; 韩栓; 何世斌; 张大乐

    2013-01-01

    目的:通过对家兔离体心脏缺血再灌注模型制作方法的改进,延长家兔离体心脏存活时间并提高其存活状态,为研究离体心脏缺血再灌注提供更为稳定的模型.方法:健康新西兰家兔20只随机分为对照组与实验组,每组10只;通过改进实验方法与优化剖取家兔心脏术式操作,记录两组离体心脏复跳和从复跳到稳定跳动时间、比较两组离体心脏的存活时间及状态.结果:改进组优化手术操作完全暴露家兔心脏、减少了心肌机械性损伤,用改进台氏液冲洗离体心脏,缩短了从心脏取出到主动脉挂于灌流装置上该过程的时间,从而缩短了心脏从离体到再灌注此段的缺血时间;灌流液的温度从30℃缓慢升至37℃,此过程避免了离体心脏从4℃环境直升为37℃的初期供氧与灌流液温度条件变化而带来的心肌内环境紊乱,加之在灌流装置中增加了心脏保温罩、不断更换以95 %O2+5%CO2氧饱和气化的新鲜台氏液,以共同维持离体心肌的正常生理功能.结果两组对比,改进组家兔离体心脏复跳时间和从复跳到稳定跳动时间比对照组缩短、明显显示其稳定有节律跳动时间延长(P<0.01).结论:本改进法可使家兔离体心脏复苏快、且能持续有节律稳定跳动7h左右,达到延长家兔离体心脏存活时间的目的,该模型可适用于专业实验教学和科学研究.%Objective: To establish a method to prolong the survival time of rabbit heart ischemia-reperfusion model in vitro. Methods: 20 New Zealand rabbits were evenly and randomly divided into control group and tested group. The control groups were performed with classic surgery method with 4℃ Tyrode's buffer perfusion. While tested group was operated with the improved rabbit cardiac surgery, which included the uncovered cardiac surgery, elevating the temperature of Tyrode's cardiac perfusion buffer from 4℃ to 30℃ and consistently renewing

  20. Mild Hypothermia Combined with Hydrogen Sulfide Treatment During Resuscitation Reduces Hippocampal Neuron Apoptosis Via NR2A, NR2B, and PI3K-Akt Signaling in a Rat Model of Cerebral Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Dai, Hai-Bin; Xu, Miao-Miao; Lv, Jia; Ji, Xiang-Jun; Zhu, Si-Hai; Ma, Ru-Meng; Miao, Xiao-Lei; Duan, Man-Lin

    2016-09-01

    We investigated whether mild hypothermia combined with sodium hydrosulfide treatment during resuscitation improves neuron survival following cerebral ischemia-reperfusion injury beyond that observed for the individual treatments. Male Sprague-Dawley rats were divided into seven groups (n = 20 for each group). All rats underwent Pulsinelli 4-vessel occlusion. Ischemia was induced for 15 min using ligatures around the common carotid arteries, except for the sham group. Immediately after initiating reperfusion, the mild hypothermia (MH), sodium hydrosulfide (NaHS), hydroxylamine (HA), MH + NaHS, MH + HA, and ischemia-reperfusion (I/R) control groups received an intraperitoneal injection of saline, sodium hydrosulfide, hydroxylamine, sodium hydrosulfide, hydroxylamine, and saline, respectively, and mild hypothermia (32 to 33 °C) was induced in the MH, MH + NaHS, and MH + HA groups for 6 h. The levels of NR2A, NR2B, p-Akt, and p-Gsk-3β in the hippocampus of the MH, NaHS, and MH + NaHS groups were higher than those in the I/R control group, with the highest levels observed in the MH + NaHS group (P sodium hydrosulfide treatment for resuscitation following ischemia-reperfusion injury was more beneficial for reducing hippocampal apoptosis and pathology than that of mild hypothermia or hydrogen sulfide treatment alone.

  1. SPECT imaging of myocardial infarction using {sup 99m}Tc-labeled C2A domain of synaptotagmin I in a porcine ischemia-reperfusion model

    Energy Technology Data Exchange (ETDEWEB)

    Fang Wei [Department of Nuclear Medicine, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Beijing 100037 (China); Wang Feng [Nuclear Medicine Department, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006 (China); Ji Shundong [Jiangsu Institute of Hematology, 1st Hospital of Suzhou University, Suzhou 215006 (China); Zhu Xiaoguang [Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, WI 53226 (United States); Meier, Heidi T. [Clinical Veterinarian and Radiology Research, Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin, WI 53295 (United States); Hellman, Robert S. [Department of Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, WI 53226 (United States); Brindle, Kevin M. [MRC Laboratory of Molecular Biology, Cambridge CB2 2QH (United Kingdom); Davletov, Bazbek [Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA (United Kingdom); Zhao Ming [Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, WI 53226 (United States)], E-mail: mzhao@mcw.edu

    2007-11-15

    Introduction: The C2A domain of synaptotagmin I recognizes necrotic and apoptotic cells by binding to exposed anionic phospholipids. The goal is to explore the potential imaging utility of {sup 99m}Tc-labeled C2A in the detection of acute cardiac cell death in a porcine model that resembles human cardiovascular physiology. Methods: Ischemia (20-25 min) was induced in pigs (M/F, 20-25 kg) using balloon angioplasty. {sup 99m}Tc-C2A-GST (n=7) or {sup 99m}Tc-BSA (n=2) was injected intravenously 1-2 h after reperfusion. Noninfarct animals were injected with {sup 99m}Tc-C2A-GST (n=4). SPECT images were acquired at 3 and 6 h postinjection. Cardiac tissues were analyzed to confirm the presence of cell death. Results: Focal uptake was detected in five out of seven subjects at 3 h and in all infarct subjects at 6 h postinjection but not in infarct animals injected with {sup 99m}Tc-BSA or in noninfarct animals with {sup 99m}Tc-C2A-GST. Gamma counting of infarct versus normal myocardium yielded a 10.2{+-}5.7-fold elevation in absolute radioactivity, with histologically confirmed infarction. Conclusions: We present data on imaging myocardial cell death in the acute phase of infarction in pigs. C2A holds promise and warrants further development as an infarct-avid molecular probe.

  2. Emergent role of gasotransmitters in ischemia-reperfusion injury.

    Science.gov (United States)

    Moody, Bridgette F; Calvert, John W

    2011-04-27

    Nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) are lipid-soluble, endogenously produced gaseous messenger molecules collectively known as gasotransmitters. Over the last several decades, gasotransmitters have emerged as potent cytoprotective mediators in various models of tissue and cellular injury. Specifically, when used at physiological levels, the exogenous and endogenous manipulation of these three gases has been shown to modulate ischemia/reperfusion injury by inducing a number of cytoprotective mechanisms including: induction of vasodilatation, inhibition of apoptosis, modulation of mitochondrial respiration, induction of antioxidants, and inhibition of inflammation. However, while the actions are similar, there are some differences in the mechanisms by which these gasotransmitters induce these effects and the regulatory actions of the enzyme systems can vary depending upon the gas being investigated. Furthermore, there does appear to be some crosstalk between the gases, which can provide synergistic effects and additional regulatory effects. This review article will discuss several models and mechanisms of gas-mediated cytoprotection, as well as provide a brief discussion on the complex interactions between the gasotransmitter systems.

  3. Emergent role of gasotransmitters in ischemia-reperfusion injury

    Directory of Open Access Journals (Sweden)

    Moody Bridgette F

    2011-04-01

    Full Text Available Abstract Nitric oxide (NO, carbon monoxide (CO and hydrogen sulfide (H2S are lipid-soluble, endogenously produced gaseous messenger molecules collectively known as gasotransmitters. Over the last several decades, gasotransmitters have emerged as potent cytoprotective mediators in various models of tissue and cellular injury. Specifically, when used at physiological levels, the exogenous and endogenous manipulation of these three gases has been shown to modulate ischemia/reperfusion injury by inducing a number of cytoprotective mechanisms including: induction of vasodilatation, inhibition of apoptosis, modulation of mitochondrial respiration, induction of antioxidants, and inhibition of inflammation. However, while the actions are similar, there are some differences in the mechanisms by which these gasotransmitters induce these effects and the regulatory actions of the enzyme systems can vary depending upon the gas being investigated. Furthermore, there does appear to be some crosstalk between the gases, which can provide synergistic effects and additional regulatory effects. This review article will discuss several models and mechanisms of gas-mediated cytoprotection, as well as provide a brief discussion on the complex interactions between the gasotransmitter systems.

  4. Tadalafil significantly reduces ischemia reperfusion injury in skin island flaps

    Directory of Open Access Journals (Sweden)

    Oguz Kayiran

    2013-01-01

    Full Text Available Introduction: Numerous pharmacological agents have been used to enhance the viability of flaps. Ischemia reperfusion (I/R injury is an unwanted, sometimes devastating complication in reconstructive microsurgery. Tadalafil, a specific inhibitor of phosphodiesterase type 5 is mainly used for erectile dysfunction, and acts on vascular smooth muscles, platelets and leukocytes. Herein, the protective and therapeutical effect of tadalafil in I/R injury in rat skin flap model is evaluated. Materials and Methods: Sixty epigastric island flaps were used to create I/R model in 60 Wistar rats (non-ischemic group, ischemic group, medication group. Biochemical markers including total nitrite, malondialdehyde (MDA and myeloperoxidase (MPO were analysed. Necrosis rates were calculated and histopathologic evaluation was carried out. Results: MDA, MPO and total nitrite values were found elevated in the ischemic group, however there was an evident drop in the medication group. Histological results revealed that early inflammatory findings (oedema, neutrophil infiltration, necrosis rate were observed lower with tadalafil administration. Moreover, statistical significance (P < 0.05 was recorded. Conclusions: We conclude that tadalafil has beneficial effects on epigastric island flaps against I/R injury.

  5. Humanized cobra venom factor decreases myocardial ischemia-reperfusion injury.

    Science.gov (United States)

    Gorsuch, W Brian; Guikema, Benjamin J; Fritzinger, David C; Vogel, Carl-Wilhelm; Stahl, Gregory L

    2009-12-01

    Cobra venom factor (CVF) is a complement activating protein in cobra venom, which functionally resembles C3b, and has been used for decades for decomplementation of serum to investigate the role of complement in many model systems of disease. The use of CVF for clinical practice is considered impractical because of immunogenicity issues. Humanization of CVF was recently demonstrated to yield a potent CVF-like molecule. In the present study, we demonstrate that mice treated with recombinant humanized CVF (HC3-1496) are protected from myocardial ischemia-reperfusion (MI/R) injuries with resultant preservation of cardiac function. Also, C3 deposition in the myocardium following MI/R was not observed following treatment with HC3-1496. HC3-1496 led to complement activation and depletion of C3, but preserved C5 titers. These data suggest, unlike CVF, HC3-1496 does not form a C5 convertase in the mouse, similar to recent studies in human sera/plasma. These results suggest that humanized CVF (HC3-1496) protects the ischemic myocardium from reperfusion injuries induced by complement activation and represents a novel anti-complement therapy for potential clinical use.

  6. Regulation of Expression of Renal Organic Anion Transporters OAT1 and OAT3 in a Model of Ischemia/Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Christina Preising

    2015-08-01

    Full Text Available Background: Recently, we gained evidence that impairment of rOat1 and rOat3 expression induced by ischemic acute kidney injury (AKI is mediated by COX metabolites and this suppression might be critically involved in renal damage. Methods: (i Basolateral organic anion uptake into proximal tubular cells after model ischemia and reperfusion (I/R was investigated by fluorescein uptake. The putative promoter sequences from hOAT1 (SLC22A6 and hOAT3 (SCL22A8 were cloned into a reporter plasmid, transfected into HEK cells and (ii transcriptional activity was determined after model ischemia and reperfusion as a SEAP reporter gen assay. Inhibitors or antagonists were applied with the beginning of reperfusion. Results: By using inhibitors of PKA (H89 and PLC (U73122, antagonists of E prostanoid receptor type 2 (AH6809 and type 4 (L161,982, we gained evidence that I/R induced down regulation of organic anion transport is mediated by COX1 metabolites via E prostanoid receptor type 4. The latter signaling was confirmed by application of butaprost (EP2 agonist or TCS2510 (EP4 agonist to control cells. In brief, the latter signaling was verified for the transcriptional activity in the reporter gen assay established. Therein, selective inhibitors for COX1 (SC58125 and COX2 (SC560 were also applied. Conclusion: Our data show (a that COX1 metabolites are involved in the regulation of renal organic anion transport(ers after I/R via the EP4 receptor and (b that this is due to transcriptional regulation of the respective transporters. As the promoter sequences cloned were of human origin and expressed in a human renal epithelial cell line we (c hypothesize that the regulatory mechanisms described after I/R is meaningful for humans as well.

  7. Glycine preconditioning to ameliorate pulmonary ischemia reperfusion injury in rats

    NARCIS (Netherlands)

    Sommer, Sebastian-Patrick; Sommer, Stefanie; Sinha, Bhanu; Leyh, Rainer G.

    2012-01-01

    This study examines the impact of glycine (Gly) preconditioning on ischemia reperfusion (IR)-induced pulmonary mitochondrial injury to research the previously, in pig lungs, demonstrated Gly-dependent amelioration of pulmonary IR injury. IR injury was induced in rat lungs by 30 min pulmonary hilum c

  8. The neuroprotection of Aspirin on Cerebral Ischemia-Reperfusion rats

    Institute of Scientific and Technical Information of China (English)

    QiuLi-ying; YuJuan; ChenChong-hong; ZhouYu

    2004-01-01

    AIM: Aspirin (aeetylsalicylic acid, ASA as a nonsteroidal anti-inflammatory drug not only has well-established efficacy in anti-thromboxane, but also has direct neuroprotective effect. In this study, we design to investigate its neuroprotective effect on focal cerebral ischemia-reperfusion injury (CIRI rats, and its effect on ATP level from occluded brain tis-

  9. Release of Tissue-specific Proteins into Coronary Perfusate as a Model for Biomarker Discovery in Myocardial Ischemia/Reperfusion Injury

    DEFF Research Database (Denmark)

    Cordwell, Stuart; Edwards, Alistair; Liddy, Kiersten

    2012-01-01

    Diagnosis of acute coronary syndromes is based on protein biomarkers, such as the cardiac troponins (cTnI/cTnT) and creatine kinase (CK-MB) that are released into the circulation. Biomarker discovery is focused on identifying very low abundance tissue-derived analytes from within albumin-rich pla......Diagnosis of acute coronary syndromes is based on protein biomarkers, such as the cardiac troponins (cTnI/cTnT) and creatine kinase (CK-MB) that are released into the circulation. Biomarker discovery is focused on identifying very low abundance tissue-derived analytes from within albumin...

  10. Tempol protects the gallbladder against ischemia/reperfusion.

    Science.gov (United States)

    Gomez-Pinilla, Pedro J; Camello, Pedro J; Tresguerres, Jesus A F; Pozo, María José

    2010-06-01

    Impairment in gallbladder emptying, increase in residual volume, and reduced smooth muscle contractility are hallmarks of acute acalculous cholecystitis and seem to be related to ischemia/reperfusion (I/R). This study was designed to determine the effects of tempol, a general antioxidant, on I/R-induced changes in gallbladder contractile capacity, the mechanisms involved in the contractile process, and the level of inflammatory mediators. Experimental gallbladder I/R was induced in male guinea pigs by common bile duct ligation for 2 days, then a deligation of the duct was performed and after 2 days the animals were sacrificed. A group of animals was treated with tempol, administered in the drinking water at 1 mmol/l for 10 days prior the bile duct ligation and until animal sacrifice. Isometric tension recordings showed that KCl and cholecystokinin-induced contractions were impaired by I/R, which correlated with decreased F-actin content and detrimental effects on Ca(2+) influx. In addition, I/R depolarized mitochondrial membrane potential, as indicated by the reduction of the heterogeneity of the rhodamine123 fluorescence signal, and increased the expression of NF-kappaB, COX-2, and iNOS. Tempol treatment improved contractility via normalization of Ca(2+) handling and improvement of F-actin content. Moreover, the antioxidant ameliorated mitochondrial polarity and normalized the expression levels of the inflammatory mediators. These results show that antioxidant treatment protects the gallbladder from I/R, indicating the potential therapeutic benefits of tempol in I/R injury.

  11. KR-31761, a novel K+(ATP)-channel opener, exerts cardioprotective effects by opening both mitochondrial K+(ATP) and Sarcolemmal K+(ATP) channels in rat models of ischemia/reperfusion-induced heart injury.

    Science.gov (United States)

    Yang, Min-Kyu; Lee, Sung-Hun; Seo, Ho-Won; Yi, Kyu-Yang; Yoo, Sung-Eun; Lee, Byung-Ho; Chung, Hun-Jong; Won, Hyung-Sik; Lee, Chang-Soo; Kwon, Suk-Hyung; Choi, Wahn-Soo; Shin, Hwa-Sup

    2009-02-01

    The cardioprotective effects of KR-31761, a newly synthesized K+(ATP) opener, were evaluated in rat models of ischemia/reperfusion (I/R) heart injury. In isolated rat hearts subjected to 30-min global ischemia/30-min reperfusion, KR-31761 perfused prior to ischemia significantly increased both the left ventricular developed pressure (% of predrug LVDP: 17.8, 45.1, 54.2, and 62.6 for the control, 1 microM, 3 microM, and 10 microM, respectively) and double product (DP: heart rate x LVDP; % of predrug DP: 17.5, 44.9, 56.2, and 64.5 for the control, 1 microM, 3 microM, and 10 microM, respectively) at 30-min reperfusion while decreasing the left ventricular end-diastolic pressure (LVEDP). KR-31761 (10 microM) significantly increased the time to contracture during the ischemic period, whereas it concentration-dependently decreased the lactate dehydrogenase release during reperfusion. All these parameters were significantly reversed by 5-hydroxydecanoate (5-HD, 100 microM) and glyburide (1 microM), selective and nonselective blockers of the mitochondrial K+(ATP) (mitoK+(ATP)) channel and K+(ATP) channel, respectively. In anesthetized rats subjected to 30-min occlusion of left anterior descending coronary artery/2.5-h reperfusion, KR-31761 administered 15 min before the onset of ischemia significantly decreased the infarct size (72.2%, 55.1%, and 47.1% for the control, 0.3 mg/kg, i.v., and 1.0 mg/kg, i.v., respectively); and these effects were completely and almost completely abolished by 5-HD (10 mg/kg, i.v.) and HMR-1098, a selective blocker of sarcolemmal K+(ATP) (sarcK+(ATP)) channel (6 mg/kg, i.v.) administered 5 min prior to KR-31761 (72.3% and 67.9%, respectively). KR-31761 only slightly relaxed methoxamine-precontracted rat aorta (IC50: > 30.0 microM). These results suggest that KR-31761 exerts potent cardioprotective effects through the opening of both mitoK+(ATP) and sarcK+(ATP) channels in rat hearts with a minimal vasorelaxant effect.

  12. Poly-IC preconditioning protects against cerebral and renal ischemia-reperfusion injury.

    Science.gov (United States)

    Packard, Amy E B; Hedges, Jason C; Bahjat, Frances R; Stevens, Susan L; Conlin, Michael J; Salazar, Andres M; Stenzel-Poore, Mary P

    2012-02-01

    Preconditioning induces ischemic tolerance, which confers robust protection against ischemic damage. We show marked protection with polyinosinic polycytidylic acid (poly-IC) preconditioning in three models of murine ischemia-reperfusion injury. Poly-IC preconditioning induced protection against ischemia modeled in vitro in brain cortical cells and in vivo in models of brain ischemia and renal ischemia. Further, unlike other Toll-like receptor (TLR) ligands, which generally induce significant inflammatory responses, poly-IC elicits only modest systemic inflammation. Results show that poly-IC is a new powerful prophylactic treatment that offers promise as a clinical therapeutic strategy to minimize damage in patient populations at risk of ischemic injury.

  13. Kidney Injury Molecule-1 Protects against Gα12 Activation and Tissue Damage in Renal Ischemia-Reperfusion Injury

    Science.gov (United States)

    Ismail, Ola Z.; Zhang, Xizhong; Wei, Junjun; Haig, Aaron; Denker, Bradley M.; Suri, Rita S.; Sener, Alp; Gunaratnam, Lakshman

    2016-01-01

    Ischemic acute kidney injury is a serious untreatable condition. Activation of the G protein α12 (Gα12) subunit by reactive oxygen species is a major cause of tissue damage during renal ischemia-reperfusion injury. Kidney injury molecule-1 (KIM-1) is a transmembrane glycoprotein that is highly up-regulated during acute kidney injury, but the physiologic significance of this up-regulation is unclear. Here, we report for the first time that Kim-1 inhibits Gα12 activation and protects mice against renal ischemia-reperfusion injury. We reveal that Kim-1 physically interacts with and inhibits cellular Gα12 activation after inflammatory stimuli, including reactive oxygen species, by blocking GTP binding to Gα12. Compared with Kim-1+/+ mice, Kim-1−/− mice exhibited greater Gα12 and downstream Src activation both in primary tubular epithelial cells after in vitro stimulation with H2O2 and in whole kidneys after unilateral renal artery clamping. Finally, we show that Kim-1–deficient mice had more severe kidney dysfunction and tissue damage after bilateral renal artery clamping, compared with wild-type mice. Our results suggest that KIM-1 is an endogenous protective mechanism against renal ischemia-reperfusion injury through inhibition of Gα12. PMID:25759266

  14. TLR9 Mediates Remote Liver Injury following Severe Renal Ischemia Reperfusion.

    Directory of Open Access Journals (Sweden)

    Pieter J Bakker

    Full Text Available Ischemia reperfusion injury is a common cause of acute kidney injury and is characterized by tubular damage. Mitochondrial DNA is released upon severe tissue injury and can act as a damage-associated molecular pattern via the innate immune receptor TLR9. Here, we investigated the role of TLR9 in the context of moderate or severe renal ischemia reperfusion injury using wild-type C57BL/6 mice or TLR9KO mice. Moderate renal ischemia induced renal dysfunction but did not decrease animal well-being and was not regulated by TLR9. In contrast, severe renal ischemia decreased animal well-being and survival in wild-type mice after respectively one or five days of reperfusion. TLR9 deficiency improved animal well-being and survival. TLR9 deficiency did not reduce renal inflammation or tubular necrosis. Rather, severe renal ischemia induced hepatic injury as seen by increased plasma ALAT and ASAT levels and focal hepatic necrosis which was prevented by TLR9 deficiency and correlated with reduced circulating mitochondrial DNA levels and plasma LDH. We conclude that TLR9 does not mediate renal dysfunction following either moderate or severe renal ischemia. In contrast, our data indicates that TLR9 is an important mediator of hepatic injury secondary to ischemic acute kidney injury.

  15. Attenuation of Brain Inflammatory Response after Focal Cerebral Ischemia/Reperfusion with Xuesaitong Injection(血塞通注射液) in Rats

    Institute of Scientific and Technical Information of China (English)

    HE Wei; XU Xiao-jun

    2006-01-01

    Objective: To investigate the neuro-protective effect of Xuesaitong Injection ( 血塞通注射液 ,XST) on brain inflammatory response after transient focal cerebral ischemia/reperfusion in rats. Methods:Focal cerebral ischemia/reperfusion models of male rats were induced by transient occlusion for 2 h of middle cerebral artery (MCA) which was followed by 24 h reperfusion. XST was administered through intraperitoneal injection of 25 mg/kg or 50 mg/kg at 4 h after the onset of ischemia. After reperfusion for 24 h, the neurological function score was evaluated, the brain edema was detected with dry-wet weight method, the myeloperoxidase (MPO) activity and the expression of intercellular adhesion molecule-1 (ICAM-1) of ischemic cerebral cortex and caudate putamen was determined by spectrophotometry and immunohistochemistry respectively. Results: XST not only lowered neurological function score at the dose of 50 mg/kg, but reduced brain edema and inhibited MPO activity and ICAM-1 expression as compared with the ischemia/reperfusion model group ( P<0.01 ). Conclusion: XST has a definite effect on inhibiting the expression of ICAM-1 and neutrophil infiltration in rats with cerebral ischemia/reperfusion when treatment started at 4 h after ischemia onset, and also attenuates inflammation in the infarcted cerebral area.neutrophil, intercellular adhesion molecule-1 of ischemic cerebral cortex and caudate putamen was determined by spectrophotometry and immunohistochemistry respectively. Results: XST not only lowered neurological function score at the dose of 50 mg/kg, but reduced brain edema and inhibited MPO activity and ICAM-1 expression as compared with the ischemia/reperfusion model group ( P<0.01 ). Conclusion: XST has a definite effect on inhibiting the expression of ICAM-1 and neutrophil infiltration in rats with cerebral ischemia/reperfusion when treatment started at 4 h after ischemia onset, and also attenuates inflammation in the infarcted cerebral area.

  16. Riluzole improves outcome following ischemia-reperfusion injury to the spinal cord by preventing delayed paraplegia.

    Science.gov (United States)

    Wu, Y; Satkunendrarajah, K; Fehlings, M G

    2014-04-18

    The spinal cord is vulnerable to ischemic injury due to trauma, vascular malformations and correction of thoracic aortic lesions. Riluzole, a sodium channel blocker and anti-glutamate drug has been shown to be neuroprotective in a model of ischemic spinal cord injury, although the effects in clinically relevant ischemia/reperfusion models are unknown. Here, we examine the effect of riluzole following ischemia-reperfusion injury to the spinal cord. Female rats underwent high thoracic aortic balloon occlusion to produce an ischemia/reperfusion injury. Tolerance to ischemia was evaluated by varying the duration of occlusion. Riluzole (8mg/kg) was injected intraperitoneally 4h after injury. Locomotor function (Basso, Beattie and Bresnahan (BBB) scale) was assessed at 4h, 1day, and 5days post-ischemia. Spinal cords were extracted and evaluated for neuronal loss using immunohistology (choline acetyltransferase (ChAT) and neuronal nuclei (NeuN)), inflammation (CD11b), astrogliosis (glial fibrillary acidic protein - GFAP) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Ischemic injury lasting between 5.5 and 6.75min resulted in delayed paraplegia, whereas longer ischemia induced immediate paraplegia. When riluzole was administered to rats that underwent 6min of occlusion, delayed paraplegia was prevented. The BBB score of riluzole-treated rats was 11.14±4.85 compared with 1.86±1.07 in control animals. Riluzole also reduced neuronal loss, infiltration of microglia/macrophages and astrogliosis in the ventral horn and intermediate zone of the gray matter. In addition, riluzole reduced apoptosis of neurons in the dorsal horn of the gray matter. Riluzole has a neuroprotective effect in a rat model of spinal cord injury/reperfusion when administered up to 4h post-injury, a clinically relevant therapeutic time window.

  17. Research of MCP-1 expression in rat's retina injured by ischemia-reperfusion%MCP-1在大鼠视网膜缺血再灌注损伤中的表达及意义研究

    Institute of Scientific and Technical Information of China (English)

    游志鹏; 姜德咏; 李国栋; 赵宏伟

    2003-01-01

    目的了解MCP-1在大鼠视网膜缺血再灌注损伤中的表达及意义.方法建立大鼠视网膜缺北血再灌注模型,以SABC法检测MCP-1在视网膜中的表达,统计学分析.结果MCP-1在视网膜缺血再灌注6 h开始表达,第24小时达到最高峰,48 h开始表达减弱.结论MCP-1在视网膜缺血再灌注损伤中起重要作用.%Objective:The retina ischemia- reperfusion injury is caused by many factors. A lot of cell factors take part in it. Many researches suggest MCP - 1 has special effect on leukocyte and lymphocyte. The research try to study the effect of MCP - 1 in rat's retina ischemia- reperfusion injury. Methods: To employ the rat's retina ischemia- reperfusion model and use SABC method to test the expression of MCP- 1 on retina. Results: There was no MCP - 1 expressed in retina after ischemia- reperfusion injury for one hour. MCP- 1 began to express in retina after ischemia- reperfusion injury for six hours, and expressed at most after ischemia- reperfusion injury for 24 hours. Then it began to decrease in 48 hours after ischemia - repeffusion injury, but it still expressed in retina in seventy- two hours after ischemia- reperfusion injury. Conclusions: MCP- 1 plays an important role in rat's retina ischemia- reperfusion injury.

  18. Low molecular weight fucoidan against renal ischemia-reperfusion injury via inhibition of the MAPK signaling pathway.

    Directory of Open Access Journals (Sweden)

    Jihui Chen

    Full Text Available BACKGROUND: Ischemia reperfusion injury (IRI is a leading cause of acute kidney injury (AKI in both native and transplanted kidneys. The objective of the present study was to evaluate whether low-molecular-weight fucoidan (LMWF could attenuate renal IRI in an animal model and in vitro cell models and study the mechanisms in which LMWF protected from IRI. METHODOLOGY/PRINCIPAL FINDINGS: Male mice were subjected to right renal ischemia for 30 min and reperfusion for 24 h, or to a sham operation with left kidney removed. Kidneys undergone IR showed characteristic morphological changes, such as tubular dilatation, and brush border loss. However, LMWF significantly corrected the renal dysfunction and the abnormal levels of MPO, MDA and SOD induced by IR. LMWF also inhibited the activation of MAPK pathways, which consequently resulted in a significant decrease in the release of cytochrome c from mitochondria, ratios of Bax/Bcl-2 and cleaved caspase-3/caspase-3, and phosphorylation of p53. LMWF alleviated hypoxia-reoxygenation or CoCl(2 induced cell viability loss and ΔΨm dissipation in HK2 renal tubular epithelial cells, which indicates LMWF may result in an inhibition of the apoptosis pathway through reducing activity of MAPK pathways in a dose-dependent manner. CONCLUSIONS/SIGNIFICANCE: Our in vivo and in vitro studies show that LMWF ameliorates acute renal IRI via inhibiting MAPK signaling pathways. The data provide evidence that LMWF may serve as a potential therapeutic agent for acute renal IRI.

  19. Beneficial effects of n-acetyl cysteine on pancreas and kidney following experimental pancreatic ischemia-reperfusion in rats

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    Roberto Ferreira Meirelles Junior

    2010-01-01

    Full Text Available OBJECTIVE: To evaluate the protective effects of N-acetyl cysteine on the pancreas and kidney after pancreatic ischemia reperfusion injury in a rat model. METHODS AND MATERIALS: Pancreatic ischemia reperfusion was performed in Wistar rats for 1 hour. Revascularization was achieved followed by 4 h of reperfusion. A total of 24 animals were divided into four groups: Group 1: sham; Group 2: pancreatic ischemia reperfusion without treatment; Group 3: pancreatic ischemia reperfusion plus N-acetyl cysteine intravenously; and Group 4: pancreatic ischemia reperfusion plus N-acetyl cysteine per os. Blood and tissue samples were collected after reperfusion. RESULTS: There were significant differences in amylase levels between Group 1 (6.11±0.55 and Group 2 (10.30±0.50 [p=0.0002] as well as between Group 2 (10.30±0.50 and Group 4 (7.82±0.38 [p=0.003]; creatinine levels between Group 1 (0.52 ± 0.07 and Group 2 (0.77±0.18 [p=0.035] as well as between Group 2 (0.77±0.18 and Group 3 (0.48±0.13 [p=0.012]; and pancreatic tissue thiobarbituric acid reactive substance levels between Group 1 (1.27±0.96 and Group 2 (2.60±3.01 [p=0.026] as well as between Group 2 (2.60±3.01 and Group 4 (0.52±0.56 [p=0.002]. A decrease in pancreatic tissue GST-α3 gene expression was observed in Group 2 in comparison to Group 1 (p =0.006, and an increase was observed in Groups 3 and 4 when compared to Group 2 (p= 0.025 and p=0.010, respectively. CONCLUSION: This study provides evidence that N-acetyl cysteine has a beneficial effect on pancreatic ischemia reperfusion injury and renal function in a rat model.

  20. 无创远程肢体缺血联合处理对大鼠肾脏急性缺血再灌注损伤的保护作用%The protective effect of noninvasive remote ischemic limb perconditioning and postconditioning combined on acute renal ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    江海波; 陈仁富; 朱海涛; 薛松; 孙晓磊; 孙晓青

    2015-01-01

    Objectives To investigate the noninvasive remote ischemic limb perconditioning and postconditioning combined on acute renal ischemia-reperfusion injury and its mechanism in rats.Results 30 healthy male SD rats were randomly divided into three groups (n =10):A is sham operation group (Sham group),B is ischemia -reperfusion group (IR),C is noninvasive remote ischemic limb perconditioning and postconditioning combined treatment group (RIperC + RIpostC group).After 24h reperfusion,serum creatinine (Cr) and urea nitrogen (BUN) levels,kidney tissue myeloperoxidase (MPO) activity,malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured and the light microscopy observed renal histological changes.Methods These indicators in group B Cr(429.52 ±29.08) μmol/L、BUN(39.05 ±2.23) mmol/L、MPO(7.31 ± 1.48) U/g、MDA (3.94± 0.48) nmol/mgprot were higher than group A Cr(103.91 ± 21.45) μ mol/L (P < 0.001)、BUN (12.20 ± 1.86) mmol/L(p <0.001)、MPO(2.25 ±0.89) U/g(P =0.009)、MDA(1.95 ±0.29) nmol/mgprot (p =0.003) while SOD(4.03 ±0.38) U/mgprut lower in group A SOD(6.819 ±0.68) U/mgprot(P =0.003) ; group C Cr(244.85 ± 40.30) μmol/L(p =0.002) 、BUN(23.48 ± 1.80) mmol/L(p <0.001) 、MPO(3.65 ±0.73) U/g(P =0.045)、MDA(2.19 ±0.31) nmol/mgprot(p =0.006) were lower than group B(P <0.05),while SOD SOD(5.71 ±0.30) U/mgprot(P =0.003) higher than in group B.Group A is normal morphology,group C is more significantly reduced than group B in morphological changes.Conclusions The noninvasive remote ischemic limb perconditioning and postconditioning combined on acute renal ischemia-reperfusion injury have significant protective effect.Through its protective effect may be transient limb ischemia-reperfusion stimulate e-ndogenous antioxidant capacity,so as to alleviate acute renal ischemia-reperfusion injury.%目的 探讨无创远程肢体缺血联合处理对大鼠肾脏急性缺血再灌注损伤的保护及作用机制.方法 30只健

  1. Efeito renoprotetor da estatina: modelo animal de isquemia-reperfusão Renoprotective effect of statin: a ischemia-reperfusion animal model

    Directory of Open Access Journals (Sweden)

    Claudia Akemi Shibuya Teshima

    2010-09-01

    Full Text Available OBJETIVO: A lesão renal aguda isquêmica, de causa multifatorial, apresenta morbidade e mortalidade alarmantes. A estatina, inibidor de HMG-CoA redutase, tem demonstrado papel renoprotetor, com componente antioxidante, antiinflamatório e vascular. A atividade de heme oxigenase-1 pode ser mediadora desses efeitos pleitrópicos da estatina sobre o rim, ou seja, independente da ação de redução de lipídio. Esse estudo visou avaliar se o efeito renoprotetor da estatina pode ter mecanismo heme de proteção em ratos. MÉTODOS: O modelo isquêmico foi obtido por meio do clampeamento dos pedículos renais bilaterais por 30 minutos, seguido de reperfusão. Foram utilizados ratos Wistar, machos, pesando entre 250-300g, distribuídos nos seguintes grupos: SHAM (controle, sem clampeamento renal; Isquemia; Iquemia+Estatina (sinvastatina 0,5 mg/kg, via oral por 3 dias; Isquemia+Hemin (indutor de HO-1, 1 mg/100g, intraperitoneal 24h antes da cirurgia; Isquemia+SnPP (inibidor de HO-1, 2μmol/kg intraperitoneal 24h antes da cirurgia; Isquemia+Estatina+Hemin e Isquemia+Estatina+SnPP. Foram avaliados a função renal (clearance de creatinina, Jaffé, osmolalidade urinária, peróxidos urinários e a imunohistoquímica para ED-1. RESULTADOS: Os resultados mostraram que a estatina melhorou a função renal, a osmolalidade urinária, reduziu a excreção de peróxidos urinários e a infiltração de macrófagos em rins de animais submetidos à isquemia renal. O indutor da heme oxigenase-1 e a sua associação com sinvastatina reproduziram o padrão de melhora determinado pela sinvastatina. CONCLUSÃO: O estudo confirmou o efeito renoprotetor da estatina, com ação antioxidante e antiinflamatória, e sugere que esse efeito tenha interface com o sistema heme de proteção renal.OBJECTIVE: Ischemic acute kidney injury (iLRA, with multifatorial cause, presents alarming morbidity and mortality. Statin, HMG-CoA inhibition reductase has shown a renoprotective effect

  2. FTY720 impairs necrosis development after ischemia-reperfusion injury.

    Science.gov (United States)

    Oliveira, C M S; Borra, R C; Franco, M; Schor, N; Silva, H T; Pestana, J O M; Bueno, V

    2004-05-01

    Ischemia-reperfusion (IR) injury is a common early feature that contributes to graft damage by impairing resident cell function. Our previous results showed that IR injury impaired renal function, by causing extensive tubular necrosis and increasing MHC class II and ICAM-1 molecule expression by mesangial cells (MC). MCs are likely candidates to come into close contact with immune cells such as monocytes or lymphocytes. It has been suggested that under inflammatory circumstances, there is increased MC expression of MHC class II, of adhesion molecules (such as ICAM-1), of cytokines receptors, and of molecules associated with cellular death (apoptosis). The immunosuppressive properties of FTY720 have been shown in clinical and experimental situations. It has also been shown to be protective against IR injury in rats. We sought to evaluate the role of FTY720 in a murine IR model by measuring renal function, tubular necrosis, and surface molecule expression by cultured mesangial cells. Intravenous administration of FTY720 (1 mg/kg) immediately before IR induction did not improve the short-term (24 hours) outcome of renal function or reduced MHC class II and ICAM-1 surface molecule expression. However, there was a decreased percentage of tubular necrosis in mice treated with FTY720 (51.3% +/- 1.6%) compared with vehicle-treated mice (66% +/- 5.5%). These results suggest a protective role of FTY720 in an IR injury model. More studies are required to identify the mechanisms involved in the protective activity of FTY720 in the IR injury model.

  3. Granulocyte colony-stimulating factor regulates JNK pathway to alleviate damage after cerebral ischemia reperfusion

    Institute of Scientific and Technical Information of China (English)

    LI Ya-guo; LIU Xiao-li; ZHENG Chao-bo

    2013-01-01

    Background Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent hematopoietic growth factor that both enhances the survival and drives the differentiation and proliferation of myeloid lineage cells.Recent studies have suggested that GM-CSF has a neuroprotective effect against cerebral ischemia injury,but the molecular mechanisms have been unclear.This study aimed to investigate the influences of a short-acting (half-life 3.5 hours) G-CSF and a long-acting (half-life 40 hours) pegylated G-CSF on the JNK signaling pathway after cerebral ischemia reperfusion.Methods A total of 52 Sprague-Dawley rats were randomly divided into four groups:a sham group (n=4),a vehicle with saline (n=16),a short-acting G-CSF treatment group (n=16) and a long-acting G-CSF treatment group (n=16).The cerebral ischemia reperfusion model was established for the sham group and G-CSF treatment groups by middle cerebral artery occlusion (MCAO).Five days post reperfusion,rats were sacrificed and the brains were removed.Changes in neurological function after cerebral ischemia reperfusion was evaluated according to Neurological Severity Score (NSS) and the lesion volume and infarct size were measured by 2,3,5-triphenyltetrazolium chloride staining.The numbers of apoptotic neurons in these ischemic areas:left cerebral cortex,striatum and hippocampus were calculated by TUNEL assay,and expression of JNK/P-JNK,c-jun/P-c-jun in these areas was detected by Western blotting.Results Compared with the saline vehicle group ((249.68±23.36) mm3,(19.27±3.37)%),G-CSF-treated rats revealed a significant reduction in lesion volume (long-acting:(10.89±1.90)%,P <0.01; short-acting G-CSF:(11.69±1.41)%,P <0.01)and infarct size (long-acting:(170.53±18.47) mm3,P <0.01; short-acting G-CSF:(180.74±16.93) mm3,P <0.01) as well as less neuron functional damage (P <0.01) and a smaller number of apoptotic neurons in ischemic areas (P <0.01).The activity of P-JNK and P-c-jun in the

  4. Insulin Reduces Cerebral Ischemia/Reperfusion Injury in the Hippocampus of Diabetic Rats

    OpenAIRE

    Collino, Massimo; Aragno, Manuela; Castiglia, Sara; Tomasinelli, Chiara; Thiemermann, Christoph; Boccuzzi, Giuseppe; Fantozzi, Roberto

    2009-01-01

    OBJECTIVE—There is evidence that insulin reduces brain injury evoked by ischemia/reperfusion (I/R). However, the molecular mechanisms underlying the protective effects of insulin remain unknown. Insulin is a well-known inhibitor of glycogen synthase kinase-3β (GSK-3β). Here, we investigate the role of GSK-3β inhibition on I/R-induced cerebral injury in a rat model of insulinopenic diabetes. RESEARCH DESIGN AND METHODS—Rats with streptozotocin-induced diabetes were subjected to 30-min occlusio...

  5. Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf2-ARE pathway

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate the effect of sulforaphane (SFN) on regulation of NF-E2-related factor-2 (Nrf2)-antiox-idant response element (ARE) pathway in liver injury induced by intestinal ischemia/reperfusion (I/R). METHODS: Rats were divided randomly into four ex-perimental groups: control, SFN control, intestinal I/R and SFN pretreatment groups (n = 8 in each group). The intestinal I/R model was established by clamping the superior mesenteric artery for 1 h and 2 h reperfu-sion. In the SFN pretreatment group, s...

  6. 高迁移率族蛋白B1对心肌缺血再灌注损伤保护作用的初步临床研究%Cardioprotective effect of high mobility group protein B1 against myocardial ischemia-reperfusion injury in acute myocardial infarction patients

    Institute of Scientific and Technical Information of China (English)

    刘宇; 曹清心; 张燕; 赵仙先

    2012-01-01

    ( AMI ) and wide application of the reper-fusion therapy, extensive attention has been drawn to ischemia-reperfusion injury ( IRI ), but no effective method ever found for its treatment. Recent studies based on animal models show that high mobility group protein BI ( HMGBI ) may' play a critical role in IRI. Our aim is to determine whether HMGBI is involved in IRI in AMI patients undergoing percutaneous coronary intervention ( PCI ), and to evaluate the myocardial protective effect of HMGBI and its possible mechanisms. Methods We used ELISA to detect the levels of plasma HMGBI and vascular endothelial growth factor ( VEGF ) in 17 health)' volunteers with normal coronary arteriography ( control group ) and 41 AMI patients undergoing emergency PCI ( AMI operation group ) immediately, 24 hours and 48 hours after surgery. We also recorded the infarction related arteries ( IRA ), the types of reperfusion arrhythmia at the time of IRA opening, the level of brain natriuretic peptide, adverse cardiac events during hospital stay and other basic clinical data. Results Reperfusion arrhythmia was found in all the AMI patients at the time of IRA opening. The HMGB1 level was significantly higher in the AMI group at 24 than at 48 hours after operation ( P < 0. 05 ), with a positive correlation with that of VEGF at different time points ( P < 0. 05 ), but it was remarkably lower in those with adverse cardiac events during hospital stay than in those without at different time points ( P <0.05 ). Conclusion HMGB1 is involved in myocardial ischemia-reperfusion injury in AMI patients undergoing percutaneous coronary intervention, and its level has a predictive value in the long-term prognosis of AMI. It may' participate in the process of myocardial repair by its secretomotor pathway for VEGF, and thereby play a role in improving cardiac function and protecting cardialcytes.

  7. Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

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    Ozkan Onal

    2015-01-01

    Full Text Available Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF intraperitoneally (ip for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD, catalase (CAT, glutathioneperoxidase (GSH-Px, malondyaldehide (MDA, and protein carbonyl (PCO were analyzed in tissue samples. Total oxidant status (TOS, and total antioxidant capacity (TAC were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy

  8. Combination Anti-Apoptotic Effect of Erythropoietin and Melatonin on Ischemia Reperfusion-Induced Renal Injury in Rats

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    Shokofeh Banaei

    2016-11-01

    Full Text Available Renal ischemia-reperfusion (IR contributes to the development of acute renal failure (ARF. Oxygen free radicals are considered to be principal components involved in the pathophysiological tissue alterations observed during renal IR. The purpose of this study was to investigate the combination effect of melatonin (MEL and erythropoietin (EPO, which are a potent antioxidant and anti-apoptotic agents, in IR-induced renal injury in rats. Wistar Albino rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. MEL (10 mg/kg, i.p and EPO (5000 U/kg, i.p were administered prior to ischemia. After 24 h reperfusion, following decapitation, blood samples were collected for the determination of superoxide dismutase (SOD, glutathione peroxidase (GPx, and malondialdehyde (MDA levels. Also, renal samples were taken for histological evaluation and apoptosis assay. Ischemia-reperfusion increased SOD, GPx, MDA levels, and TUNEL positive cells. Histopathological findings of the IR group confirmed that there was renal impairment in the tubular epithelium. Treatment with EPO and MEL decreased SOD, GPx, and MDA levels, histopathological changes, and TUNEL positive cells. These results indicated that the combination of MEL and EPO could not exert more nephroprotective and anti-apoptotic effects than MEL treatment in renal ischemia-reperfusion injury.

  9. Pretreatment with erythropoietin reduces hepatic ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Yu-Hong Luo; Zheng-Dong Li; Li-Xin Liu; Gao-Hong Dong

    2009-01-01

    BACKGROUND: During hepatectomy, a period of ischemia and restoration of the blood supply can result in hepatic ischemia-reperfusion injury (IRI). Current research indicates that erythropoietin (EPO) has a protective effect in animal models of cerebral ischemia, myocardial infarction, and renal IRI. However there is lack of research into the role of EPO in hepatic IRI. This study aimed to explore the role of EPO in hepatic IRI and its possible mechanism of action. METHODS: Thirty male Sprague-Dawley rats were divided into three groups: (1) ten rats in the experimental group were given 1000 IU/kg EPO one day before the operation; (2) ten rats in a control group were given normal saline preoperatively as a placebo; and (3) ten rats served as a sham-operated group. Hepatic IRI was induced by occluding the hepatic arteries of the three cephalad hepatic segments and the portal vein for about 45 minutes, while in the sham-operated group only laparotomy was performed. The levels of ALT and AST were tested 24 hours pre- and post-operation. All rats were sacriifced 24 hours after the operation to assess the pathologic changes in the liver and measure the expression of heme oxygenase-1 (HO-1) through Western blotting and RT-PCR. RESULTS: Hepatic IRI was markedly mitigated in the experimental group as compared with the control group. Moreover, the expression of HO-1 at the level of both transcription and protein increased prominently (P<0.05) in the experimental group. CONCLUSION: These results demonstrate that EPO can up-regulate HO-1 in liver tissues and accordingly decrease hepatic injury through its anti-inlfammatory property.

  10. Diabetic Inhibition of Preconditioning- and Postconditioning-Mediated Myocardial Protection against Ischemia/Reperfusion Injury

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    Xia Yin

    2012-01-01

    Full Text Available Ischemic preconditioning (IPC or postconditioning (Ipost is proved to efficiently prevent ischemia/reperfusion injuries. Mortality of diabetic patients with acute myocardial infarction was found to be 2–6 folds higher than that of non-diabetic patients with same myocardial infarction, which may be in part due to diabetic inhibition of IPC- and Ipost-mediated protective mechanisms. Both IPC- and Ipost-mediated myocardial protection is predominantly mediated by stimulating PI3K/Akt and associated GSK-3β pathway while diabetes-mediated pathogenic effects are found to be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. Therefore, this review briefly introduced the general features of IPC- and Ipost-mediated myocardial protection and the general pathogenic effects of diabetes on the myocardium. We have collected experimental evidence that indicates the diabetic inhibition of IPC- and Ipost-mediated myocardial protection. Increasing evidence implies that diabetic inhibition of IPC- and Ipost-mediated myocardial protection may be mediated by inhibiting PI3K/Akt and associated GSK-3β pathway. Therefore any strategy to activate PI3K/Akt and associated GSK-3β pathway to release the diabetic inhibition of both IPC and Ipost-mediated myocardial protection may provide the protective effect against ischemia/reperfusion injuries.

  11. Caffeine Mitigates Lung Inflammation Induced by Ischemia-Reperfusion of Lower Limbs in Rats

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    Wei-Chi Chou

    2015-01-01

    Full Text Available Reperfusion of ischemic limbs can induce inflammation and subsequently cause acute lung injury. Caffeine, a widely used psychostimulant, possesses potent anti-inflammatory capacity. We elucidated whether caffeine can mitigate lung inflammation caused by ischemia-reperfusion (IR of the lower limbs. Adult male Sprague-Dawley rats were randomly allocated to receive IR, IR plus caffeine (IR + Caf group, sham-operation (Sham, or sham plus caffeine (n=12 in each group. To induce IR, lower limbs were bilaterally tied by rubber bands high around each thigh for 3 hours followed by reperfusion for 3 hours. Caffeine (50 mg/kg, intraperitoneal injection was administered immediately after reperfusion. Our histological assay data revealed characteristics of severe lung inflammation in the IR group and mild to moderate characteristic of lung inflammation in the IR + Caf group. Total cells number and protein concentration in bronchoalveolar lavage fluid of the IR group were significantly higher than those of the IR + Caf group (P<0.001 and P=0.008, resp.. Similarly, pulmonary concentrations of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, and macrophage inflammatory protein-2 and pulmonary myeloperoxidase activity of the IR group were significantly higher than those of the IR + Caf group (all P<0.05. These data clearly demonstrate that caffeine could mitigate lung inflammation induced by ischemia-reperfusion of the lower limbs.

  12. The Hepatoprotective Effect of Sodium Nitrite on Cold Ischemia-Reperfusion Injury

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    Wei Li

    2012-01-01

    Full Text Available Liver ischemia-reperfusion injury is a major cause of primary graft non-function or initial function failure post-transplantation. In this study, we examined the effects of sodium nitrite supplementation on liver IRI in either Lactated Ringer's (LR solution or University of Wisconsin (UW solution. The syngeneic recipients of liver grafts were also treated with or without nitrite by intra-peritoneal injection. Liver AST and LDH release were significantly reduced in both nitrite-supplemented LR and UW preservation solutions compared to their controls. The protective effect of nitrite was more efficacious with longer cold preservation times. Liver histological examination demonstrated better preserved morphology and architecture with nitrite treatment. Hepatocellular apoptosis was significantly reduced in the nitrite-treated livers compared their controls. Moreover, liver grafts with extended cold preservation time of 12 to 24 hours demonstrated improved liver tissue histology and function post-reperfusion with either the nitrite-supplemented preservation solution or in nitrite-treated recipients. Interestingly, combined treatment of both the liver graft and recipient did not confer protection. Thus, nitrite treatment affords significant protection from cold ischemic and reperfusion injury to donor livers and improves liver graft acute function post-transplantation. The results from this study further support the potential for nitrite therapy to mitigate ischemia-reperfusion injury in solid organ transplantation.

  13. Protective effects of apocynin and allopurinol on ischemia/reperfusion-induced liver injury in mice

    Institute of Scientific and Technical Information of China (English)

    Ping-Guo Liu; Song-Qing He; Yan-Hong Zhang; Jian Wu

    2008-01-01

    AIM: To determine the effects of allopurinol, an inhibitor of xanthine oxidase, and apocynin, an inhibitor of NADPH oxidase, on oxidant stress and liver injury caused by hepatic ischemia/reperfusion (I/R) procedure in mice. METHODS: Nice were pretreated with a xanthine oxidase inhibitor, allopurinol, or NADPH oxidase (NOX)inhibitor, apocynin before the hepatic I/R procedure. Then treated or untreated mice underwent the hepatic I/R procedure. The effects on hepatic injury and superoxide anions were determined after starting reperfusion. RESULTS: A standard warm hepatic I/R procedure led to a marked increase in superoxide anion production as indicated by a superoxide anion tracer, MCLA. At the same time, the procedure caused profound acute liver injury, as indicated by elevated serum alanine aminotransferase and tumor necrosis factor-αlevels, reduced liver glutathione levels and elevated malondialdehyde contents, as well as a high apoptotic cell count. All these changes were reversed by the use of apocynin or allopurinol prior to the hepatic I/R procedure. CONCLUSION: AIIopurinol and apocynin exerted protective effects on hepatic ischemia/reperfusion injury. The protection is associated with blocking the generation of superoxide anions during the hepatic I/R procedure by inhibiting xanthine oxidase and NADPH oxidase activity.

  14. Ultra Low Dose Delta 9-Tetrahydrocannabinol Protects Mouse Liver from Ischemia Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Edith Hochhauser

    2015-07-01

    Full Text Available Background/Aims: Ischemia/reperfusion (I/R injury is the main cause of both primary graft dysfunction and primary non-function of liver allografts. Cannabinoids has been reported to attenuate myocardial, cerebral and hepatic I/R oxidative injury. Delta-9-tetrahydrocannabinol (THC, a cannabinoid agonist, is the active components of marijuana. In this study we examined the role of ultralow dose THC (0.002mg/kg in the protection of livers from I/R injury. This extremely low dose of THC was previously found by us to protect the mice brain and heart from a variety of insults. Methods: C57Bl Mice were studied in in vivo model of hepatic segmental (70% ischemia for 60min followed by reperfusion for 6 hours. Results: THC administration 2h prior to the induction of hepatic I/R was associated with significant attenuated elevations of: serum liver transaminases ALT and AST, the hepatic oxidative stress (activation of the intracellular signaling CREB pathway, the acute proinflammatory response (TNF-α, IL-1α, IL-10 and c-FOS hepatic mRNA levels, and ERK signaling pathway activation. This was followed by cell death (the cleavage of the pro-apoptotic caspase 3, DNA fragmentation and TUNEL after 6 hours of reperfusion. Significantly less hepatic injury was detected in the THC treated I/R mice and fewer apoptotic hepatocytes cells were identified by morphological criteria compared with untreated mice. Conclusion: A single ultralow dose THC can reduce the apoptotic, oxidative and inflammatory injury induced by hepatic I/R injury. THC may serve as a potential target for therapeutic intervention in hepatic I/R injury during liver transplantation, liver resection and trauma.

  15. Polyethylene glycol reduces early and long-term cold ischemia-reperfusion and renal medulla injury.

    Science.gov (United States)

    Faure, Jean Pierre; Hauet, Thierry; Han, Zeqiu; Goujon, Jean Michel; Petit, Isabelle; Mauco, Gerard; Eugene, Michel; Carretier, Michel; Papadopoulos, Vassilios

    2002-09-01

    Ischemia-reperfusion injury (IRI) after transplantation is a major cause of delayed graft function, which has a negative impact on early and late graft function and improve acute rejection. We have previously shown that polyethylene glycol (PEG) and particularly PEG 20M has a protective effect against cold ischemia and reperfusion injury in an isolated perfused pig and rat kidney model. We extended those observations to investigate the role of PEG using different doses (30g or 50g/l) added (ICPEG30 or ICPEG50) or not (IC) to a simplified preservation solution to reduce IRI after prolonged cold storage (48-h) of pig kidneys when compared with Euro-Collins and University of Wisconsin solutions. The study of renal function and medulla injury was performed with biochemical methods and proton NMR spectroscopy. Histological and inflammatory cell studies were performed after reperfusion (30-40 min) and on days 7 and 14 and weeks 4, 8, and 12. Peripheral-type benzodiazepine receptor (PBR), a mitochondrial protein involved in cholesterol homeostasis, was also studied. The results demonstrated that ICPEG30 improved renal function and reduced medulla injury. ICPEG30 also improved tubular function and strongly protect mitochondrial integrity. Post-IRI inflammation was strongly reduced in this group, particularly lymphocytes TCD4(+), PBR expression was influenced by IRI in the early period and during the development of chronic dysfunction. This study clearly shows that PEG has a beneficial effect in renal preservation and suggests a role of PBR as a marker IRI and repair processes.

  16. Hypoxia-inducible factor plays a gut-injurious role in intestinal ischemia reperfusion injury.

    Science.gov (United States)

    Kannan, Kolenkode B; Colorado, Iriana; Reino, Diego; Palange, David; Lu, Qi; Qin, Xiaofa; Abungu, Billy; Watkins, Anthony; Caputo, Francis J; Xu, Da-Zhong; Semenza, Gregg L; Deitch, Edwin A; Feinman, Rena

    2011-05-01

    Gut injury and loss of normal intestinal barrier function are key elements in the paradigm of gut-origin systemic inflammatory response syndrome, acute lung injury, and multiple organ dysfunction syndrome (MODS). As hypoxia-inducible factor (HIF-1) is a critical determinant of the physiological and pathophysiological response to hypoxia and ischemia, we asked whether HIF-1 plays a proximal role in the induction of gut injury and subsequent lung injury. Using partially HIF-1α-deficient mice in an isolated superior mesenteric artery occlusion (SMAO) intestinal ischemia reperfusion (I/R) injury model (45 min SMAO followed by 3 h of reperfusion), we showed a direct relationship between HIF-1 activation and intestinal I/R injury. Specifically, partial HIF-1α deficiency attenuated SMAO-induced increases in intestinal permeability, lipid peroxidation, mucosal caspase-3 activity, and IL-1β mRNA levels. Furthermore, partial HIF-1α deficiency prevented the induction of ileal mucosal inducible nitric oxide synthase (iNOS) protein levels after SMAO and iNOS deficiency ameliorated SMAO-induced villus injury. Resistance to SMAO-induced gut injury was also associated with resistance to lung injury, as reflected by decreased levels of myeloperoxidase, IL-6 and IL-10 in the lungs of HIF-1α(+/-) mice. In contrast, a short duration of SMAO (15 min) followed by 3 h of reperfusion neither induced mucosal HIF-1α protein levels nor caused significant gut and lung injury in wild-type or HIF-1α(+/-) mice. This study indicates that intestinal HIF-1 activation is a proximal regulator of I/R-induced gut mucosal injury and gut-induced lung injury. However, the duration and severity of the gut I/R insult dictate whether HIF-1 plays a gut-protective or deleterious role.

  17. HIF-1 mediates pathogenic inflammatory responses to intestinal ischemia-reperfusion injury.

    Science.gov (United States)

    Feinman, Rena; Deitch, Edwin A; Watkins, Anthony C; Abungu, Billy; Colorado, Iriana; Kannan, Kolenkode B; Sheth, Sharvil U; Caputo, Francis J; Lu, Qi; Ramanathan, Madhuri; Attan, Shirhan; Badami, Chirag D; Doucet, Danielle; Barlos, Dimitrios; Bosch-Marce, Marta; Semenza, Gregg L; Xu, Da-Zhong

    2010-10-01

    Acute lung injury (ALI) and the development of the multiple organ dysfunction syndrome (MODS) are major causes of death in trauma patients. Gut inflammation and loss of gut barrier function as a consequence of splanchnic ischemia-reperfusion (I/R) have been implicated as the initial triggering events that contribute to the development of the systemic inflammatory response, ALI, and MODS. Since hypoxia-inducible factor (HIF-1) is a key regulator of the physiological and pathophysiological response to hypoxia, we asked whether HIF-1 plays a proximal role in the induction of gut injury and subsequent lung injury. Utilizing partially HIF-1α-deficient mice in a global trauma hemorrhagic shock (T/HS) model, we found that HIF-1 activation was necessary for the development of gut injury and that the prevention of gut injury was associated with an abrogation of lung injury. Specifically, in vivo studies demonstrated that partial HIF-1α deficiency ameliorated T/HS-induced increases in intestinal permeability, bacterial translocation, and caspase-3 activation. Lastly, partial HIF-1α deficiency reduced TNF-α, IL-1β, cyclooxygenase-2, and inducible nitric oxide synthase levels in the ileal mucosa after T/HS whereas IL-1β mRNA levels were reduced in the lung after T/HS. This study indicates that prolonged intestinal HIF-1 activation is a proximal regulator of I/R-induced gut mucosal injury and gut-induced lung injury. Consequently, these results provide unique information on the initiating events in trauma-hemorrhagic shock-induced ALI and MODS as well as potential therapeutic insights.

  18. Xanthohumol suppresses inflammatory response to warm ischemia-reperfusion induced liver injury.

    Science.gov (United States)

    Dorn, Christoph; Massinger, Sabine; Wuzik, Andreas; Heilmann, Jörg; Hellerbrand, Claus

    2013-02-01

    Liver ischemia/reperfusion (I/R) leads to formation of reactive oxygen species (ROS), which cause hepatic injury and initiate an inflammatory response, which is a critical problem after liver surgery and transplantation. Xanthohumol, the major prenylated chalcone found in hops, has been discussed for its anti-inflammatory and ROS-scavenging properties, and thus, we aimed to investigate the effect of xanthohumol in a model of warm I/R liver injury. Xanthohumol was applied to BALB/c mice orally at a dose of 1 mg/g body weight for 5 days before I/R-injury was induced by clamping the vascular blood supply to the median and left lateral liver lobe for 1 h followed by a 6 h period of reperfusion. At this time, HPLC analysis revealed hepatic xanthohumol levels of approximately 2 μM, a concentration which has been shown to inhibit inflammatory effects in vitro. Assessment of hepatic HMOX1 expression, hepatic glutathione content and immunohistochemical analysis for proteins conjugated with the reactive aldehyde 4-hydroxynonenal indicated that I/R-induced oxidative stress was significantly inhibited in xanthohumol-fed compared to control mice. Histological analysis, TUNEL staining and determination of transaminase serum levels revealed no significant effects of xanthohumol on acute hepatocellular injury. However, at the same time point, pretreatment with xanthohumol almost completely blunted the I/R-induced AKT and NFκB activation and the expression of the proinflammatory genes IL-1alpha, IL-6, MCP-1 and ICAM-1, which are known to play a crucial role in the subacute phase of I/R-induced liver damage. In conclusion, these data indicate the potential of xanthohumol application to prevent adverse inflammatory responses to I/R-induced liver damage such as after surgical liver resection or transplantation.

  19. The Therapeutic Effect of Vitamin C in an Animal Model of Complex Regional Pain Syndrome Produced by Prolonged Hindpaw Ischemia-Reperfusion in Rats

    Science.gov (United States)

    Kim, Jae Hun; Kim, Yong Chul; Nahm, Francis Sahngun; Lee, Pyung Bok

    2017-01-01

    Objectives: It is known that increased free radicals from oxidative stress are one of the major causes of complex regional pain syndrome (CRPS). In this study, we tested the hypothesis that vitamin C has a dose-related treatment effect in a chronic post-ischemic pain (CPIP) model. Methods: A total of 49 male rats weighing 250 to 350 g were used. The 4 treatment groups were control (no medication), group 1.0 (administration of 1 mg/day for vitamin C for 5 days), group 2.5 (administration of 2.5 mg/day vitamin C for 5 days), and group 7.5 (administration of 7.5 mg/day vitamin C for 5 days). The 50% mechanical withdrawal threshold and total blood antioxidant status (TAS) were measured before and after administration of vitamin C. Results: Twenty-eight CPIP model rats were generated from 49 rats. Seven rats were randomly allocated to each group. The 50% mechanical withdrawal threshold of group 2.5 (after the administration of vitamin C) was higher than that of the control group and group 1.0 (P < 0.05). At 1 day of the administration of vitamin C, the 50% mechanical withdrawal threshold of group 1.0 was higher than that of the control group and the blood levels of TAS in groups 2.5 and 7.5 were higher than that in control group (P < 0.05). Twelve days after the administration of vitamin C, the blood levels of TAS in groups 2.5 and 7.5 were lower than that of the control group (P < 0.05). Discussion: The administration of a proper dose of vitamin C can reduce oxidative stress, increase antioxidants, and recover the threshold for mechanical allodynia in the CPIP model.

  20. Protective effects of curcumin supplementation on intestinal ischemia reperfusion injury.

    Science.gov (United States)

    Okudan, N; Belviranlı, M; Gökbel, H; Oz, M; Kumak, A

    2013-07-15

    The aim of this study was to investigate the effects curcumin on inflammation and oxidative stress markers in the intestinal ischemia reperfusion (IIR) injury induced rats. Rats were divided into four groups: sham (S), intestinal IR (IIR), curcumin plus sham (CS), and curcumin plus intestinal IR (CIIR). Curcumin was given 200 mg kg⁻¹ for 20 days. IIR was produced by 45 min of intestinal ischemia followed by a 120 min of reperfusion. Although interleukin-6 levels tended to increase in IIR group tumor necrosis factor-α levels were not different. Intestinal myeloperoxidase activity in CS group was lower than IIR group. In intestine and heart tissues, malondialdehyde levels in CS and CIIR groups were lower than S and IIR groups. Superoxide dismutase activity in CIIR group was higher than IIR group in intestine and lung tissues. Curcumin has a protective role against ischemia reperfusion injury.

  1. The complement system in ischemia-reperfusion injuries.

    Science.gov (United States)

    Gorsuch, William B; Chrysanthou, Elvina; Schwaeble, Wilhelm J; Stahl, Gregory L

    2012-11-01

    Tissue injury and inflammation following ischemia and reperfusion of various organs have been recognized for many years. Many reviews have been written over the last several decades outlining the role of complement in ischemia/reperfusion injury. This short review provides a current state of the art knowledge on the complement pathways activated, complement components involved and a review of the clinical biologics/inhibitors used in the clinical setting of ischemia/reperfusion. This is not a complete review of the complement system in ischemia and reperfusion injury but will give the reader an updated view point of the field, potential clinical use of complement inhibitors, and the future studies needed to advance the field.

  2. Puerarin protects brain tissue against cerebral ischemia/reperfusion injur y by inhibiting the inlfammator y response

    Institute of Scientific and Technical Information of China (English)

    Feng Zhou; Liang Wang; Panpan Liu; Weiwei Hu; Xiangdong Zhu; Hong Shen; Yuanyuan Yao

    2014-01-01

    Puerarin, a traditional Chinese medicine, exerts a powerful neuroprotective effect in cerebral isch-emia/reperfusion injury, but its mechanism is unknown. Here, we established rat models of middle cerebral artery ischemia/reperfusion injury using the suture method. Puerarin (100 mg/kg) was administered intraperitoneally 30 minutes before middle cerebral artery occlusion and 8 hours after reperfusion. Twenty-four hours after reperfusion, we found that puerarin signiifcantly im-proved neurological deifcit, reduced infarct size and brain water content, and notably diminished the expression of Toll-like receptor-4, myeloid differentiation factor 88, nuclear factor kappa B and tumor necrosis factor-αin the ischemic region. These data indicate that puerarin exerts an anti-inlfammatory protective effect on brain tissue with ischemia/reperfusion damage by down-regulating the expression of multiple inlfammatory factors.

  3. Establishment of a new ischemia reperfusion injury model of pancreas in rats%一种大鼠胰腺缺血再灌注模型的建立

    Institute of Scientific and Technical Information of China (English)

    卢冰; 刘红山; 胡伟明; 田伯乐; 张肇达

    2011-01-01

    Objective To build a convenient model of pancreas ischemia reperfusion injury (IRI)in rats for investigating its negative impact on pancreas. Methods Wistar rats were randomized into 4groups:(1)sham-operated animals with dissociation of the pancreatic tail-segment ( sham, n=20 ); ( 2 )control animals with dissociation of the pancrea-tic tail-segment, 30 seconds of ischemia by bcloking the abdominal aorta and flushing(control, n=20);(3) Group New model animals experienced with dissociation of the pancreatic tail-segment, flushing, 120 mins of ischemia and reperfusion (IR, n=20). The level of serum amylase and lipase, wet to weight ratio of pancreas and pathological changes of pancreas were observed at0, 2, 4, 6 hours after reperfusion. Results The level of serum amylase[2 h (3127.80±150.85) U/L, 4 h (3122.80±131.52) U/L, 6 h (2585.20±161.06) U/L]and lipase[2 h (446.00±181.54) U/L, 4 h (517.40±165.22) U/L, 6 h (475.20 ± 170.37) U/L]in Group New model were increased significantly after perfusion accordingly, The tissue damage of pancreas become more serious after perfusion. Conclusion The model shows a typical IRl on pancreas of rats. It's a ideal and clinically relevant animal model for the study of pancreas IRI after transplantation.%目的 建立一种简便实用的大鼠经腹主动脉胰腺缺血再灌注模型.方法 将60只Wistar大鼠随机分为:新模型组、对照组和假手术组,每组20只.采用显微外科技术游离胰腺,胰腺灌注后阻断血流2 h,恢复再灌注后0、2、4、6 h,切取胰腺体尾部组织,检测湿/干重比、行组织病理学分析及血清淀粉酶和脂肪酶检测.结果 再灌注后,新模型组血清淀粉酶2 h(3127.80±150.85)U/L、4 h(3122.80±131.52)U/L、6 h(2585.20±161.06)U/L;血清脂肪酶2 h(446.00±181.54)U/L、4 h(517.40±165.22)U/L、6 h(475.20±170.37)U/L;均随再灌注时间延长有明显升高趋势(P<0.05),胰腺组织病理切片呈现逐渐加重的炎细胞浸润及组织水肿(P<0

  4. Effect of intestinal ischemia-reperfusion injury on protein levels of leptin and orexin-A in peripheral blood and central secretory tissues

    Institute of Scientific and Technical Information of China (English)

    Ji Lin; Guang-Tao Yan; Xiu-Hua Hao; Lu-Huan Wang; Kai Zhang; Hui Xue

    2005-01-01

    AIM: To explore the effect of intestinal ischemia-reperfusion injury on protein levels of leptin and orexin-A in peripheral blood and their central secretory tissues and to find out the role leptin and orexin-A play in acute inflammatory responses.METHODS: An intestinal ischemia-reperfusion (I/R)injury model of rats was established and rats were divided randomly into six groups: sham-operation group, 60 min ischemia/30 min reperfusion group (I60'R30'), I60'R90',I60'R150', I60'R240' and I60'R360', 9 rats each group.Two highly-sensitive radioimmunoassays for leptin and orexin-A were established and used to check the change of their concentrations in peripheral blood and central secretory tissues before and after intestinal I/R injury.RESULTS: Compared with the serum leptin level before injury, it decreased significantly in I60'R30' group and increased significantly in I60'R360' group; compared to sham-operation group after injury, serum leptin level increased significantly in I60'R360' group; compared to sham-operation group after injury, adipose leptin levels decreased significantly in I60'R30' and I60'R90' groups,while increased significantly in I60'R360' group. There was no significant difference between the expression levels of orexin-A before and after I/R injury.CONCLUSION: Leptin has a time-dependent response and orexin-A has a delayed response to acute inflammatory stimuli such as intestinal I/R injury and they may participate in metabolic disorders in injury as inflammatory cytokines.

  5. Rosiglitazone-enriched diet did not protect liver ischemia-reperfusion injury in a rat model Dieta enriquecida com rosiglitazona não protege a lesão de isquemia e reperfusão hepática em modelo experimental no rato

    Directory of Open Access Journals (Sweden)

    Antonio Roberto Franchi Teixeira

    2008-08-01

    Full Text Available PURPOSE: To determine whether rosiglitazone-enriched diet offer protection in a classical model of liver ischemia-reperfusion injury in rats. METHODS: Two days before the experiment, rats were divided into 2 groups: Control Group (n=13 rats fed with standard diet; Rosi Group (n=13: rats fed with a powdered standard diet supplemented with rosiglitazone. The animals were submitted to liver ischemia-reperfusion by clamping the pedicle of median and left anterolateral lobes. After 1 hour of partial hepatic ischemia, the clamp was removed for reperfusion. After 2 or 24 hours (Control and Rosi Groups, blood was collected for enzymes and cytokines analysis. Ischemic and non-ischemic liver were collected for malondialdehyde analysis and histological assessment. Lungs were removed for tissue myeloperoxidase quantification. RESULTS: There were no statistical differences between groups for all analysed parameters. CONCLUSION: In this model, rosiglitazone-enriched diet did not protect liver against ischemia-reperfusion injury.OBJETIVO: Determinar se a dieta enriquecida com rosiglitazona oferece proteção em um modelo clássico de lesão de isquemia e reperfusão hepática em ratos. MÉTODOS: Dois dias antes do experimento, os ratos foram divididos em 2 grupos: Grupo Controle (n=13: ratos alimentados com dieta padrão; Grupo Rosi (n=13: ratos alimentados com dieta em pó padrão enriquecida com rosiglitazona. Os animais foram submetidos à isquemia e reperfusão hepática por clampeamento do pedículo dos lobos médio e anterolateral esquerdo. Após 1 hora de isquemia, o clampe foi removido para a reperfusão. Após 2 ou 24 horas (Grupos Controle e Rosi, o sangue foi coletado para análise de enzimas e citocinas. Os fígados isquêmico e não isquêmico foram coletados para análise de malondialdeído e avaliação histológica. Pulmões foram removidos para quantificação da mieloperoxidase tecidual. RESULTADOS: Não houve diferenças estatísticas entre

  6. Cardiac-specific expression of the tetracycline transactivator confers increased heart function and survival following ischemia reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Laila Elsherif

    Full Text Available Mice expressing the tetracycline transactivator (tTA transcription factor driven by the rat α-myosin heavy chain promoter (α-MHC-tTA are widely used to dissect the molecular mechanisms involved in cardiac development and disease. However, these α-MHC-tTA mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury in both in vitro and in vivo models in the absence of associated cardiac hypertrophy or remodeling. Cardiac function, as assessed by echocardiography, did not differ between α-MHC-tTA and control animals, and there were no noticeable differences observed between the two groups in HW/TL ratio or LV end-diastolic and end-systolic dimensions. Protection against ischemia/reperfusion injury was assessed using isolated perfused hearts where α-MHC-tTA mice had robust protection against ischemia/reperfusion injury which was not blocked by pharmacological inhibition of PI3Ks with LY294002. Furthermore, α-MHC-tTA mice subjected to coronary artery ligation exhibited significantly reduced infarct size compared to control animals. Our findings reveal that α-MHC-tTA transgenic mice exhibit a gain-of-function phenotype consisting of robust protection against ischemia/reperfusion injury similar to cardiac pre- and post-conditioning effects. However, in contrast to classical pre- and post-conditioning, the α-MHC-tTA phenotype is not inhibited by the classic preconditioning inhibitor LY294002 suggesting involvement of a non-PI3K-AKT signaling pathway in this phenotype. Thus, further study of the α-MHC-tTA model may reveal novel molecular targets for therapeutic intervention during ischemic injury.

  7. The protective role of montelukast against intestinal ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Wu, Shenbao; Zhu, Xuxing; Jin, Zhonghai; Tong, Xiuping; Zhu, Liqin; Hong, Xiaofei; Zhu, Xianfei; Liu, Pengfei; Shen, Weidong

    2015-10-26

    Several drugs are effective in attenuating intestinal ischemia-reperfusion injury (IRI); however little is known about the effect of montelukast. Fifty rats were randomly assigned to 3 groups: model group (operation with clamping), sham group (operation without clamping), and study group (operation with clamping and 0.2, 2 and 20 mg/kg montelukast pretreatment). Intestinal ischemia-reperfusion was performed by occlusion (clamping) of the arteria mesenterica anterior for 45 min, followed by 24 h reperfusion. Intestinal IRI in the model group led to severe damage of the intestinal mucosa, liver and kidney. The Chiu scores of the intestines from the study group (2 and 20 mg/kg) were lower than that of the model group. Intestinal IRI induced a marked increase in CysLTR1, Caspase-8 and -9 expression in intestine, liver and kidney, which were markedly reduced by preconditioning with 2 mg/kg montelukast. Preconditioning with 2 g/kg montelukast significantly attenuated hepatic tissue injury and kidney damage, and decreased plasma interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in plasma after intestinal IRI. In conclusion, preconditioning with montelukast could attenuate intestinal IRI and the subsequent systemic inflammatory response in rats.

  8. Flavonoids from Scutellaria baicalensis Georgi are effective to treat cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Yazhen Shang; Hong Zhang; Jianjun Cheng; Hong Miao; Yongping Liu; Kai Cao; Hui Wang

    2013-01-01

    Based on previous studies that have shown flavonoids from the stems and leaves of Scutellaria baicalensis Georgi are neuroprotective agents in a naturally senile, D-galactose, aging in vivo model, as well as an in vitro model of oxidative/hypoxic injury, we established a cerebral ischemia/reperfusion model in rats by middle cerebral artery occlusion. The light/electron microscopic observations found significant neuropathological changes including neuron loss or swelling and rough endoplasmic reticulum injury. Moreover, the activities of lactate dehydrogenase, Na+-K+-ATPase, Ca2+-ATPase and superoxide dismutase were significantly lowered, and the levels of malonaldehyde increased. In addition, the memory of rats worsened. However, treatment with flavonoids from Scutellaria baicalensis Georgi (35, 70 and 140 mg/kg) for 13 days dramatically improved the above abnormal changes. These results suggest that the ability of flavonoids from Scutellaria baicalensis Georgi in attenuating cerebral functional and morphological consequences after cerebral ischemia/reperfusion may be beneficial for the treatment of ischemic brain disease.

  9. Beneficial properties of selenium incorporated guar gum nanoparticles against ischemia/reperfusion in cardiomyoblasts (H9c2).

    Science.gov (United States)

    Soumya, R S; Vineetha, V P; Salin Raj, P; Raghu, K G

    2014-11-01

    Nanotechnology for the treatment and diagnosis has been emerging recently as a potential area of research and development. In the present study, selenium incorporated guar gum nanoparticles have been prepared by nanoprecipitation and characterized by transmission electron microscopy and particle size analysis. The nanoparticles were screened for antioxidant potential (metal chelation, total reducing power and hydroxyl radical scavenging activity) and were evaluated against the cell line based cardiac ischemia/reperfusion model with special emphasis on oxidative stress and mitochondrial parameters. The cell based cardiac ischemia model was employed using H9c2 cell lines. Investigations revealed that there was a significant alteration (P ≤ 0.05) in the innate antioxidant status (glutathione↓, glutathione peroxidase↓, thioredoxin reductase↓, superoxide dismutase↓, catalase↓, lipid peroxidation↑, protein carbonyl↑, xanthine oxidase↑ and caspase 3 activity↑), mitochondrial functions (reactive oxygen species generation, membrane potential, and pore opening) and calcium homeostasis (calcium ATPase and intracellular calcium overload) during both ischemia and reperfusion. For comparative evaluation, selenium, guar gum and selenium incorporated guar gum nanoparticles were evaluated for their protective properties against ischemia/reperfusion. The study reveals that selenium incorporated guar gum nanoparticles were better at protecting the cells from ischemia/reperfusion compared to selenium and guar gum nanoparticles. The potent antioxidant capability shown by the sample in in vitro assays may be the biochemical basis of its better biological activity. Further, the nanodimensions of the particle may be the additional factor responsible for its better effect.

  10. Neuroprotective effects of atorvastatin against cerebral ischemia/reperfusion injury through the inhibition of endoplasmic reticulum stress

    Institute of Scientific and Technical Information of China (English)

    Jian-wen Yang; Zhi-ping Hu

    2015-01-01

    Cerebral ischemia triggers secondary ischemia/reperfusion injury and endoplasmic reticulum stress initiates cell apoptosis. However, the regulatory mechanism of the signaling pathway remains unclear. We hypothesize that the regulatory mechanisms are mediated by the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α in the endoplasmic reticulum stress signaling pathway. To verify this hypothesis, we occluded the middle cere-bral artery in rats to establish focal cerebral ischemia/reperfusion model. Results showed that the expression levels of protein kinase-like endoplasmic reticulum kinase and caspase-3, as well as the phosphorylation of eukaryotic initiation factor 2α, were increased after ischemia/reperfusion. Administration of atorvastatin decreased the expression of protein kinase-like endoplasmic reticulum kinase, caspase-3 and phosphorylated eukaryotic initiation factor 2α, reduced the infarct volume and improved ultrastructure in the rat brain. After salubrinal, the speciifc inhibitor of phosphorylated eukaryotic initiation factor 2α was given into the rats in-tragastrically, the expression levels of caspase-3 and phosphorylated eukaryotic initiation factor 2α in the were decreased, a reduction of the infarct volume and less ultrastructural damage were observed than the untreated, ischemic brain. However, salubrinal had no impact on the expression of protein kinase-like endoplasmic reticulum kinase. Experimental ifndings indi-cate that atorvastatin inhibits endoplasmic reticulum stress and exerts neuroprotective effects. The underlying mechanisms of attenuating ischemia/reperfusion injury are associated with the protein kinase-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/caspase-3 pathway.

  11. GnRH analogue attenuated apoptosis of rat hippocampal neuron after ischemia-reperfusion injury.

    Science.gov (United States)

    Chu, Chenyu; Xu, Bainan; Huang, Weiquan

    2010-12-01

    The expression and new functions of reproductive hormones in organs beyond hypothalamus-pituitary-gonad axis have been reported. So far, there is no report about the protective effects of GnRH analogue to hippocampal neurons suffering from ischemia-reperfusion injury. Middle cerebral artery occlusion model together with TUNEL staining were made in vivo and oxygen-glucose deprivation model together with double staining of Annexin V/PI with flow cytometer were made in vitro to observe the anti-apoptotic effects of GnRH analogue to hippocampal neurons after ischemia-reperfusion injury. The results found that the number of TUNEL positive pyramidal neurons in CA1 region in GnRH analogue experiment group was less than that in control group in vivo; the percentage of apoptotic neurons in GnRH analogue experiment group was less than that in control group in vitro. These findings suggested that pretreatment with certain concentration of GnRH analogue could attenuate apoptosis of hippocampal neurons. GnRH analogue has the protective effects to neurons.

  12. Neuroprotective effect of Cerebralcare Granule after cerebral ischemia/reperfusion injury

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    Xiao-xiao Zhang; Fen-fen He; Gui-lin Yan; Ha-ni Li; Dan Li; Yan-ling Ma; Fang Wang; Nan Xu; Fei Cao

    2016-01-01

    Cerebralcare Granule (CG) improves cerebral microcirculation and relieves vasospasm, but studies investigating its therapeutic effect on cerebral ischemia/reperfusion injury are lacking. In the present study, we administered CG (0.3, 0.1 and 0.03 g/mL intragastrically) to rats for 7 consecutive days. We then performed transient occlusion of the middle cerebral artery, followed by reperfusion, and administered CG daily for a further 3 or 7 days. Compared with no treatment, high-dose CG markedly improved neurological function assessed using the Bederson and Garcia scales. At 3 days, animals in the high-dose CG group had smaller infarct volumes, greater interleukin-10 expression, and fewer interleukin-1β-immunoreactive cells than those in the untreated model group. Furthermore, at 7 days, high-dose CG-treated rats had more vascular endothelial growth factor-immunoreactive cells, elevated angiopoietin-1 and vascular endothelial growth factor ex-pression, and improved blood coagulation and lfow indices compared with untreated model animals. These results suggest that CG exerts speciifc neuroprotective effects against cerebral ischemia/reperfusion injury.

  13. Effect of Rosiglitazone Maleate on Inflammation Following Cerebral Ischemia/Reperfusion in Rats

    Institute of Scientific and Technical Information of China (English)

    XIONG Nanxiang; SUN Fan; ZHAO Hongyang; XIANG Jizhou

    2007-01-01

    In order to evaluate the neuroprotective effect of Rosiglitazone Maleate (RSG) against brain ischemic injury, the effects of Rosiglitazone Maleate on the inflammation following cerebral ischemia/reperfusion were investigated. Focal cerebral ischemia was induced by the intraluminal thread for cerebral middle artery (MCA) occlusion. Rosiglitazone Maleate at concentrations of 0.5,2 and 5 mg/kg was infused by intragastric gavage twice immediately and 2 h after MCA occlusion,respectively. The effects of Rosiglitazone Maleate on brain swelling, myeloperoxidase and interleukin-6 mRNA level in brain tissue after MCA occlusion and reperfusion were evaluated. The results showed that as compared with the model control group, RSG (0.5 mg/kg) had no significant influence on brain swelling (P>0.05), but 2 mg/kg and 5 mg/kg RSG could significantly alleviate brain swelling (P<0.05). All different doses of RSG could obviously reduce MPO activity in brain tissue after MCA occlusion and reperfusion in a dose-dependent manner. RSG (0.5 and 2 mg/kg) could decrease the expression levels of IL-6 mRNA in brain tissue after MCA occlusion and reperfusion to varying degrees (P<0.05) with the difference being significant between them. It was concluded that RSG could effectively ameliorate brain ischemic injury after 24 h MCA occlusion and inhibit the inflammatory response after ischemia-reperfusion in this model.

  14. [Effect of salvianolic acid B on neural cells damage and neurogenesis after brain ischemia-reperfusion in rats].

    Science.gov (United States)

    Zhong, Jing; Tang, Min-ke; Zhang, Yan; Xu, Qiu-ping; Zhang, Jun-tian

    2007-07-01

    This study is to observe the effect of salvianolic acid B (Sal B) on neural cells damage and neurogenesis in sub-granular zone (SGZ) and sub-ventricular zone (SVZ) after brain ischemia-reperfusion (I/R) in rats. A modified middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia-reperfusion was used. The rats were divided into four groups: sham control group, ischemia-reperfusion group, Sal B 1 and 10 mg x kg(-1) groups. Sal B was consecutively administrated once a day by ip injection after MCAO. The neurogenesis in SGZ and SVZ was investigated by BrdU method 7 days after MCAO. The Nissl staining for neurons in the hippocampal CA1 and cerebral cortex was performed 14 days after MCAO. A beam-walking test was used to monitor the motor function recovery. We found that brain ischemia resulted in an increase of BrdU positive cells both in ipsilateral SGZ and SVZ at 7th day after MCAO. Sal B (10 mg x kg(-1)) significantly increased further the number of BrdU positive cells both in SGZ and SVZ (P loss and improved motor function recovery after brain ischemia in rats.

  15. Protective Effects of Elaeagnus angustifolia Leaf Extract against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart

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    Binsheng Wang

    2014-01-01

    Full Text Available The purpose of this study is to clarify the cardioprotective property of the aqueous extract of Elaeagnus angustifolia L. leaf (EA against myocardial ischemia/reperfusion injury in isolated rat heart. The myocardial ischemia/reperfusion (I/R injury model of isolated rat heart was set up by the use of improved Langendorff retrograde perfusion technology. Compared with the ischemia/reperfusion (I/R group, the aqueous extract of Elaeagnus angustifolia L. leaf (0.5 mg/mL, 1.0 mg/mL pretreatment markedly improved the coronary flow (CF and raised left ventricular developed pressure (LVDP and maximum rise/down velocity (±dp/dtmax. The infarct size of the EA-treated hearts was smaller than that of I/R group. After treatment with EA, the superoxide dismutase (SOD activity increased; malondialdehyde (MDA and protein carbonyl content reduced more obviously (P<0.01 than that of I/R injury myocardial tissue. Conclusion. Results from the present study showed that the aqueous extract of Elaeagnus angustifolia L. leaf has obvious protective effects on myocardial I/R injury, which may be related to the improvement of myocardial oxidative stress states.

  16. Cardioprotective Effects of Salvianolic Acid A on Myocardial Ischemia-Reperfusion Injury In Vivo and In Vitro

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    Huaying Fan

    2012-01-01

    Full Text Available Salvianolic acid A (SAA, one of the major active components of Danshen that is a traditional Chinese medicine, has been reported to possess protective effect in cardiac diseases and antioxidative activity. This study aims to investigate the cardioprotection of SAA in vivo and in vitro using the model of myocardial ischemia-reperfusion in rat and hydrogen peroxide (H2O2-induced H9c2 rat cardiomyoblasts apoptosis. It was found that SAA significantly limited infarct size of ischemic myocardium when given immediately prior to reperfusion. SAA also significantly suppressed cellular injury and apoptotic cell death. Additionally, the results of western blot and phospho-specific antibody microarray analysis showed that SAA could up-regulate Bcl-2 expression and increase the phosphorylation of proteins such as Akt, p42/p44 extracellular signal-related kinases (Erk1/2, and their related effectors. The phosphorylation of those points was related to suppress apoptosis. In summary, SAA possesses marked protective effect on myocardial ischemia-reperfusion injury, which is related to its ability to reduce myocardial cell apoptosis and damage induced by oxidative stress. The protection is achieved via up-regulation of Bcl-2 expression and affecting protein phosphorylation. These findings indicate that SAA may be of value in cardioprotection during myocardial ischemia-reperfusion injury, which provide pharmacological evidence for clinical application.

  17. Cardioprotective Effects of Salvianolic Acid A on Myocardial Ischemia-Reperfusion Injury In Vivo and In Vitro

    Science.gov (United States)

    Fan, Huaying; Yang, Liu; Fu, Fenghua; Xu, Hui; Meng, Qinggang; Zhu, Haibo; Teng, Lirong; Yang, Mingyan; Zhang, Leiming; Zhang, Ziliang; Liu, Ke

    2012-01-01

    Salvianolic acid A (SAA), one of the major active components of Danshen that is a traditional Chinese medicine, has been reported to possess protective effect in cardiac diseases and antioxidative activity. This study aims to investigate the cardioprotection of SAA in vivo and in vitro using the model of myocardial ischemia-reperfusion in rat and hydrogen peroxide (H2O2)-induced H9c2 rat cardiomyoblasts apoptosis. It was found that SAA significantly limited infarct size of ischemic myocardium when given immediately prior to reperfusion. SAA also significantly suppressed cellular injury and apoptotic cell death. Additionally, the results of western blot and phospho-specific antibody microarray analysis showed that SAA could up-regulate Bcl-2 expression and increase the phosphorylation of proteins such as Akt, p42/p44 extracellular signal-related kinases (Erk1/2), and their related effectors. The phosphorylation of those points was related to suppress apoptosis. In summary, SAA possesses marked protective effect on myocardial ischemia-reperfusion injury, which is related to its ability to reduce myocardial cell apoptosis and damage induced by oxidative stress. The protection is achieved via up-regulation of Bcl-2 expression and affecting protein phosphorylation. These findings indicate that SAA may be of value in cardioprotection during myocardial ischemia-reperfusion injury, which provide pharmacological evidence for clinical application. PMID:21789047

  18. Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats

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    Noritomo Fujisaki

    2016-01-01

    Full Text Available Because inhaled carbon monoxide (CO provides potent anti-inflammatory and antioxidant effects against ischemia reperfusion injury, we hypothesized that treatment of organ donors with inhaled CO would decrease graft injury after heart transplantation. Hearts were heterotopically transplanted into syngeneic Lewis rats after 8 hours of cold preservation in University of Wisconsin solution. Donor rats were exposed to CO at a concentration of 250 parts per million for 24 hours via a gas-exposure chamber. Severity of myocardial injury was determined by total serum creatine phosphokinase and troponin I levels at three hours after reperfusion. In addition, Affymetrix gene array analysis of mRNA transcripts was performed on the heart graft tissue prior to implantation. Recipients of grafts from CO-exposed donors had lower levels of serum troponin I and creatine phosphokinase; less upregulation of mRNA for interleukin-6, intercellular adhesion molecule-1, and tumor necrosis factor-α; and fewer infiltrating cells. Although donor pretreatment with CO altered the expression of 49 genes expressly represented on the array, we could not obtain meaningful data to explain the mechanisms by which CO potentiated the protective effects.Pretreatment with CO gas before organ procurement effectively protected cardiac grafts from ischemia reperfusion-induced injury in a rat heterotopic cardiac transplant model. A clinical report review indicated that CO-poisoned organ donors may be comparable to non-poisoned donors.

  19. Spermine ameliorates ischemia/reperfusion injury in cardiomyocytes via regulation of autophagy

    Science.gov (United States)

    Duan, Qunjun; Yang, Weijun; Jiang, Daming; Tao, Kaiyu; Dong, Aiqiang; Cheng, Haifeng

    2016-01-01

    Myocardial infarction could result in high morbidity and mortality and heart diseases of children have becoming prevalent. Functions of spermine administration on cardiomyocytes remain unknown. The present study was designed to investigate the role of spermine pretreatment on myocardial ischemia/reperfusion injury (IRI). A cell model of simulated ischemia/reperfusion injury was established by incubating neonatal Sprague-Dawley rat cardiomyocytes in ischemia medium and re-cultured in normal medium. Of note, spermine pretreatment significantly reduced apoptosis and increased viability of immature cardiomyocytes. Spermine pretreatment enhanced autophagic flux as determined by confocal microscopy and transmission electron microscopy. Furthermore, proteins of mammalian target of rapamycin (mTOR) pathway were significantly reduced in response to spermine pretreatment during IRI, while proteins related to autophagy were up-regulated. The cell viability was enhanced and apoptosis decreased by rapamycin after spermine pretreatment, while these were reversed by 3-methyladenine. However, when immature cardiomyocytes were pretreated with rapamycin or 3-methyladenine, followed by IRI and spermine administration, no significant changes of viability and apoptosis were observed. In conclusion, this study suggests that spermine is a potential novel approach for preventing IRI, especially in children. PMID:27725878

  20. Dynamic alteration of the colonic microbiota in intestinal ischemia-reperfusion injury.

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    Fan Wang

    Full Text Available BACKGROUND: Intestinal ischemia-reperfusion (I/R plays an important role in critical illnesses. Gut flora participate in the pathogenesis of the injury. This study is aimed at unraveling colonic microbiota alteration pattern and identifying specific bacterial species that differ significantly as well as observing colonic epithelium change in the same injury model during the reperfusion time course. METHODOLOGY/PRINCIPAL FINDINGS: Denaturing gradient gel electrophoresis (DGGE was used to monitor the colonic microbiota of control rats and experimental rats that underwent 0.5 hour ischemia and 1, 3, 6, 12, 24, and 72 hours following reperfusion respectively. The microbiota similarity, bacterial diversity and species that characterized the dysbiosis were estimated based on the DGGE profiles using a combination of statistical approaches. The interested bacterial species in the gel were cut and sequenced and were subsequently quantified and confirmed with real-time PCR. Meanwhile, the epithelial barrier was checked by microscopy and D-lactate analysis. Colonic flora changed early and differed significantly at 6 hours after reperfusion and then started to recover. The shifts were characterized by the increase of Escherichia coli and Prevotella oralis, and Lactobacilli proliferation together with epithelia healing. CONCLUSION/SIGNIFICANCE: This study shows for the first time that intestinal ischemia-reperfusion results in colonic flora dysbiosis that follows epithelia damage, and identifies the bacterial species that contribute most.

  1. Dexamethasone pretreatment attenuates lung and kidney injury in cholestatic rats induced by hepatic ischemia/reperfusion.

    Science.gov (United States)

    Zhou, Liangyi; Yao, Xiangqing; Chen, Yanling

    2012-02-01

    Hepatic ischemia followed by reperfusion (IR) results in mild to severe organ injury, in which tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) seem to be involved. Thus, we aim to assess the influence of hepatic ischemia/reperfusion injury on remote organs in addition to cholestasis and consider the possible efficacy of steroid pretreatment in reducing the injury. A common bile duct ligation model was done on 24 male Sprague-Dawley rats. After 7 days, the rats were divided randomly into control group, IR group, and dexamethasone (DEX) group. The IR group showed significant increases in serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels compared with the control and DEX groups. By ELISA techniques, higher levels of TNF-α and IL-1β in lung and kidney tissues were measured in the IR group than in the control and DEX groups, these were verified by immunohistochemistry. The lung histology of the IR group rats showed neutrophil infiltration, interstitial edema, and alveolar wall thickening. Kidney histology of the IR group rats showed vacuolization of the proximal tubular epithelial cells and tubular dilatation with granular eosinophilic casts. Better morphological aspects were observed in the DEX-pretreated animals. Minimal lesions were observed in the control. The results suggest that hepatic ischemia/reperfusion injury in cholestatic rats induced lung and kidney injuries. Pretreatment with dexamethasone reduced the IR-induced injury in addition to cholestasis.

  2. Protection from ischemia by preconditioning, postconditioning, and combined treatment in rabbit testicular ischemia reperfusion injury.

    Science.gov (United States)

    Zhang, Xiaoying; Lv, Fangqing; Tang, Jie

    2016-10-15

    This study aimed to investigate the protection of ischemic preconditioning (IPreC), ischemic postconditioning (IPostC) and combined treatment on ischemia reperfusion injury (IRI) of testis. A rabbit testicular ischemia reperfusion (IR) model was established with determining of rabbit serum testosterone, nitric oxide (NO), malondialdehyde (MDA), protein carbonyl (PC), superoxide dismutase (SOD), myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), and tissues pathology. After IR, the NO, MDA, PC, SOD, MPO, and GSH-Px expression significantly increased in torsive testis, and significantly decreased after IPreC, IPostC, and combined treatment in torsive testis when compared to contralateral testis. In torsive testis, testicular tissues was severely damaged with spermatogenic cells disappearing, and were filled with light eosin edema liquid. Cell apoptosis index significantly increased, and the ratio of Bcl-2/Bax significantly decreased. After IPreC, IPostC, and combined treatment, testicular tissues were restored to normal, cell apoptosis index significantly decreased, and the ratio of Bcl-2/Bax significantly increased. It indicates that IPreC, IPostC, and combined treatment has an obvious protective effect on testicular IRI, by decreasing the oxidative stress index and cell apoptosis, provides a significant reference for the treatment of testicular torsion induced infertility, and exhibits a great value in clinical applications.

  3. Relevance of Endoplasmic Reticulum Stress Cell Signaling in Liver Cold Ischemia Reperfusion Injury

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    Emma Folch-Puy

    2016-05-01

    Full Text Available The endoplasmic reticulum (ER is involved in calcium homeostasis, protein folding and lipid biosynthesis. Perturbations in its normal functions lead to a condition called endoplasmic reticulum stress (ERS. This can be triggered by many physiopathological conditions such as alcoholic steatohepatitis, insulin resistance or ischemia-reperfusion injury. The cell reacts to ERS by initiating a defensive process known as the unfolded protein response (UPR, which comprises cellular mechanisms for adaptation and the safeguarding of cell survival or, in cases of excessively severe stress, for the initiation of the cell death program. Recent experimental data suggest the involvement of ERS in ischemia/reperfusion injury (IRI of the liver graft, which has been considered as one of major problems influencing outcome after liver transplantation. The purpose of this review is to summarize updated data on the molecular mechanisms of ERS/UPR and the consequences of this pathology, focusing specifically on solid organ preservation and liver transplantation models. We will also discuss the potential role of ERS, beyond the simple adaptive response and the regulation of cell death, in the modification of cell functional properties and phenotypic changes.

  4. Effect of Salvia leriifolia Benth. root extracts on ischemia-reperfusion in rat skeletal muscle

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    Nassiri-Asl Marjan

    2007-07-01

    Full Text Available Abstract Background Salvia leriifolia have been shown to decrease ischemia-reperfusion (I/R injury in brain tissues. In this study, the effects of S. leriifolia aqueous and ethanolic extracts were evaluated on an animal model of I/R injury in the rat hind limb. Methods Ischemia was induced using free-flap surgery in skeletal muscle. The aqueous and ethanolic extracts of S. leriifolia (100, 200 and 400 mg/kg root and normal saline (10 ml/kg were administered intraperitoneally 1 h prior reperfusion. During preischemia, ischemia and reperfusion conditions the electromyographic (EMG potentials in the muscles were recorded. The markers of oxidative stress including thiobarbituric acid reactive substances (TBARS, total sulfhydryl (SH groups and antioxidant capacity of muscle (using FRAP assay were measured. Results In peripheral ischemia, the average peak-to-peak amplitude during ischemic-reperfusion was found to be significantly larger in extracts groups in comparison with control group. Following extracts administration, the total SH contents and antioxidant capacity were elevated in muscle flap. The MDA level was also declined significantly in test groups. Conclusion It is concluded that S. leriifolia root extracts have some protective effects on different markers of oxidative damage in muscle tissue injury caused by lower limb ischemia-reperfusion.

  5. Inhibition of mitochondria responsible for the anti-apoptotic effects of melatonin during ischemia-reperfusion

    Institute of Scientific and Technical Information of China (English)

    HAN Yi-xiang; ZHANG Sheng-hui; WANG Xi-ming; WU Jian-bo

    2006-01-01

    Objective: To investigate a possible mechanism responsible for anti-apoptotic effects of melatonin and provide theoretical evidences for clinical therapy. Methods: Ischemia-reperfusion mediated neuronal cell injury model was constructed in cerebellar granule neurons (CGNs) by deprivation of glucose, serum and oxygen in media. After ischemia, melatonin was added to the test groups to reach differential concentration during reperfusion. DNA fragmentation, mitochondrial transmembrane potential,mitochondrial cytochrome c release and caspase-3 activity were observed after subjecting cerebellar granule neurons to oxygen-glucose deprivation (OGD). Results: The results showed that OGD induced typical cell apoptosis change, DNA ladder and apoptosis-related alterations in mitochondrial functions including depression of mitochondrial transmembrane potential (its maximal protection ratio was 73.26%) and release of cytochrome c (its maximal inhibition ratio was 42.52%) and the subsequent activation of caspase-3 (its maximal protection ratio was 59.32%) in cytoplasm. Melatonin reduced DNA damage and inhibited release of mitochondrial cytochrome c and activation of caspase-3. Melatonin can strongly prevent the OGD-induced loss of the mitochondria membrane potential. Conclusion: Our findings suggested that the direct inhibition of mitochondrial pathway might essentially contribute to its anti-apoptotic effects in neuronal ischemia-reperfusion.

  6. Effects of mild hypothermia on the expression of microtubule-associated protein 2 in neurons of the hippocampal dentate gyrus in a rat model of cerebral ischemia/reperfusion

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    Qian Yang; Feng Zheng; Jiami Wu

    2008-01-01

    BACKGROUND: It is widely accepted that mild hypothermia can protect against injury to cerebral ischemia/reperfusion.OBJECTIVE: To observe the effects of mild hypothermia on microtubule-associated protein 2 (MAP2) expression in the hippocampal dentate gyrus in rats following cerebral ischemia/reperfusion. Also, to study neuronal uhrastructural changes in the dentate gyrus to investigate the mechanism of the protection against injury to cerebral ischemia/reperfusion conferred by mild hypothermia.DESIGN, TIME AND SETTING: This randomized grouping, neural cell morphology trial was performed at the Laboratory Animal Center of Yijishan Hospital between March and June 2007.MATERIALS: Eighty-five healthy male Sprague Dawley rats were randomly allocated to three groups: mild hyputhermia (n = 40), normothermia (n = 40), and sham-operated (n = 5).METHODS: Cerebral ischemia/reperfusion injury was induced by the suture method in the mild hypothermia and normothermia groups, with a threading depth of 180.5 mm. In the sham-operated group, the suture was inserted 15 mm, with no vascular ligation, and was followed by reperfusion 2 hours later. In the sham-operated and normothermia groups, the rat rectal temperature was maintained at 36-37℃; in the mild hypothermia group, it was controlled at 32-33 ℃.MAIN OUTCOME MEASURES: The hippocampal dentate gyrus was serially sectioned for hematoxylin-eosin staining and MAP2 immunohistochemistry. Ultrastructural changes and the MAP2 absorbance value of the hippocampal dentate gyrus were examined by transmission electron microscopy.RESULTS: The sham-operated group exhibited approximately normal ultrastmcture of neurons in the bilateral hippocampal dentate gyms. In the normothermia group, ischemic hippocampal dentate gyms neurons were found with markedly fewer normal mitochondria, greatly proliferated rough endoplasmic reticulum, and a swollen and dysmorphic Golgi. In the mild hypothermia group, at each corresponding time point, these

  7. Nitric oxide inhibitor N omega -nitro-l-arginine methyl ester potentiates induction of heme oxygenase-1 in kidney ischemia/reperfusion model: a novel mechanism for regulation of the oxygenase.

    Science.gov (United States)

    Mayer, Robert D; Wang, Xiaojun; Maines, Mahin D

    2003-07-01

    The biological significance of the heme oxygenase (HO) system's response to stress reflects functions of its products-CO and bile pigments. CO is a messenger molecule, whereas bile pigments are antioxidants and modulators of cell signaling. Presently, an unexpected mechanism for sustained suprainduction of renal HO-1 following ischemia/reperfusion injury is described. Inhibition of nitric-oxide synthase (NOS) activity by Nomega-nitro-l-arginine methyl ester (l-NAME) at the resumption of reperfusion of rat kidney subjected to bilateral ischemia (30 min) was as effective as the most potent HO-1 inducer, the spin trap agent n-tert-butyl-alpha-phenyl nitrone (PBN), in causing sustained suprainduction of HO-1 mRNA. PBN forms stable radicals of oxygen and nitrogen. Twenty-four hours after reperfusion, HO-1 mRNA measured approximately 30-fold that of the control in the presence of l-NAME treatment; in its absence, the transcript increased to only approximately 5-fold. At 4 h in the presence or absence of the l-NAME HO-1, mRNA was increased by approximately 30-fold. The transcript was translated to active protein as indicated by Western blotting, immunohistochemistry, and activity analyses. l-NAME was not effective given 1 h after resumption of reperfusion. Suprainduction was restricted to the kidney and not detected in the heart and aorta; ferritin expression in the kidney was not effected. It is reasoned that in tissue directly insulted by ischemia/reperfusion, increased production of NO radicals promotes the loss of HO-1 transcript. Because the absence of NO radicals and presence of PBN had a similar effect on HO-1, we propose that suprainduction of the gene is mainly caused by O2 radicals formed on reperfusion. Inhibition of NOS is potentially useful for sustained induction of HO-1 in organs that will be subjected to oxidative-stress insult.

  8. Is subdiaphragmatic aortic cross-clamping a suitable model for spinal cord ischemia/reperfusion injury study in rats? O pinçamento sub-diagragmático da aorta é um modelo adequado para o estudo da lesão medular de isquemia/reperfusão em ratos?

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    Sonia Elizabeth Lopez Carrillo

    2006-08-01

    Full Text Available PURPOSE: To evaluate the efficacy of subdiaphragmatic aortic cross-clamping in an experimental model of ischemia/reperfusion injury of the spinal cord in albino rats. METHODS: Thirty-six male Wistar rats were randomized in two groups (n=18: G-1 (Sham and G-2 (Ischemia/Reperfusion, I/R. G-2 rats were submitted to 30 min subdiafragmatic aortic cross-clamping. G-1 rats served as controls and were submitted to surgical trauma (laparotomy without ischemia. Samples (spinal cord and arterial blood were collected at the end of ischemic period and 10 (T-10 and 20 (T-20 min later in G-2 rats. Sham rats (G-1 samples were collected at the same time-points. Blood and tissue metabolites concentrations of pyruvate, lactate, glucose and medullary adenosine triphosphate (ATP were assayed. RESULTS: Blood and tissue concentrations of pyruvate and glucose as well as lactate and medullary ATP were not different when comparing G1 to G2. Lactacemia was significantly elevated in G-2 compared with G-1 rats during reperfusion (T-10. CONCLUSION: Subdiaphragmatic aortic cord cross-clamping is not a suitable rat model for spinal cord ischemia/reperfusion injury study as it does not ensure changes in in vivo tissue metabolites concentrations similar to those found in tissues subjected to ischemia/reperfusion.OBJETIVO: Avaliar a eficácia do pinçamento da aorta subdiafragmática no modelo experimental de isquemia/reperfusão da medula espinhal em ratos. MÉTODOS: Trinta e seis ratos Wistar, machos, foram aleatoriamente distribuídos em 2 grupos (n=18 e submetidos ao pinçamento subdiafragmático da aorta, durante 30 minutos (Grupo-2 -Isquemia/Reperfusão. Os ratos do Grupo-1 (G-1 - Sham foram utilizados como controles e submetidos a laparotomia sem pinçamento arterial. As amostras (medula e sangue arterial foram coletadas ao término do período de isquemia (T-0 e 10 (T-10 e 20 (T-20 minutos mais tarde e nos mesmos intervalos, no grupo G-1. As concentrações teciduais e

  9. Effects of systemic domestic recombinant human erythropoietin on HIF-1α expression in the retina in a rabbit model of acute high intraocular pressure

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To observe the expression of hypoxia inducible factor-1α (HIF-1α) in the retina of rabbits with acute high intraocular pressure and to investigate the mechanism of systemic domestic recombinant human erythropoietin (rhEPO) protecting the retina from ischemia-reperfusion injury. Methods First,control group and model group were established in rabbit eyes. The acute high intraocular pressure model was established by saline perfusion into anterior chamber,and then hypodermic injection of domestic rhEP...

  10. 芬太尼预处理对兔心肌缺血再灌注后心肌梗死范围及心功能的影响%Effects of pretreatment with fentanyl on myocardial infarction size and cardiac function in rabbits with acute myocardial ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    郑向明; 孟凡民; 王春亭

    2012-01-01

    Objective To study the myocardial protective effect of pretreatment with fentanyl on rabbits with acute myocardial ischemia reperfusion injury.Methods Twenty-four male New Zealand White rabbits were randomly divided into 3 groups:group C ( acute myocardial ischemia reperfusion injury group),group F ( fentanyl group) and group N-F ( naloxone-fentanyl group),with 8 cases in each group.All rabbits experienced 30 min of regional ischemia through the occlusion of the left anterior descending coronary artery( LAD),followed by 120 min of reperfusion.The rabbits in C group were only subjected to the above ischemia/reperfusion (I/R) sequence.The rabbits in Group F were intravenously injected with fentany1 0.15 mg/kg at 15 minutes before the coronary occlusion.The rabbits in Group N-F were intravenously injected with naloxone 3 mg/kg,followed by 70 μg/(kg · min) infusion before reperfusion and were intravenously injected with fentanyl 0.15 mg/kg at 15 min before myocardial ischemia.Heart rate(HR),left ventricular systolic pressure( LVSP),left ventricular end diastolic pressure( LVEDP),maximum positive and minimum negative left ventricular pressure derivatives ( + dp/dt and-dp/dt) were continuously monitored and recorded at baseline ( T0 ),30 min after ischemia( T1 ),and 10 min ( T2 ),30 min(T3 ),120 min(T4) after reperfusion during I/R process.After 120 min reperfusion,hearts were removed for the measurement of myocardial ischemia and infarction size.Results Compared with the baseline(T0),LVSP,± dp/dt decreased whereas LVEDP increased significantly during T1-T4 (P <0.05 ).There were no significant differences in homodynamic parameters between group C and group N F ( P > 0.05 ).In F group,the LVSP and + dp/dt were significantly higher than those of group C and group N-F after 30 min in reperfusion ( P < 0.05 ) and the infarction size and weight were smaller (P <0.01 ).Conclusions Pretreatment with fentanyl has protective effect against ischemia/reperfusion injury

  11. Nanoparticle-Mediated Delivery of Irbesartan Induces Cardioprotection from Myocardial Ischemia-Reperfusion Injury by Antagonizing Monocyte-Mediated Inflammation

    Science.gov (United States)

    Nakano, Yasuhiro; Matoba, Tetsuya; Tokutome, Masaki; Funamoto, Daiki; Katsuki, Shunsuke; Ikeda, Gentaro; Nagaoka, Kazuhiro; Ishikita, Ayako; Nakano, Kaku; Koga, Jun-Ichiro; Sunagawa, Kenji; Egashira, Kensuke

    2016-07-01

    Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effect of early reperfusion therapy for acute myocardial infarction (AMI), in which the recruitment of inflammatory monocytes plays a causative role. Here we develop bioabsorbable poly-lactic/glycolic acid (PLGA) nanoparticles incorporating irbesartan, an angiotensin II type 1 receptor blocker with a peroxisome proliferator-activated receptor (PPAR)γ agonistic effect (irbesartan-NP). In a mouse model of IR injury, intravenous PLGA nanoparticles distribute to the IR myocardium and monocytes in the blood and in the IR heart. Single intravenous treatment at the time of reperfusion with irbesartan-NP (3.0 mg kg‑1 irbesartan), but not with control nanoparticles or irbesartan solution (3.0 mg kg‑1), inhibits the recruitment of inflammatory monocytes to the IR heart, and reduces the infarct size via PPARγ-dependent anti-inflammatory mechanisms, and ameliorates left ventricular remodeling 21 days after IR. Irbesartan-NP is a novel approach to treat myocardial IR injury in patients with AMI.

  12. Role of P-selectin and anti-P-selectin monoclonal antibody in apoptosis during hepatic/renal ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Pei Wu; Xiao Li; Tong Zhou; Wei Ming Wang; Nan Chen; De Chang Dong; Ming Jun Zhang; Jin Lian Chen

    2000-01-01

    AIM To evaluale the potential role of P-selectin and anti-P-selectin monoclonal antibody (mAb) in apoptosis during hepatic/renal ischemiareperfusion injury. METHODS Plasma P-selectin level, hepatic/renal P-selectin expression and cell apoptosis were detected in rat model of hepatic/ renal ischemia-reperfusion injury. ELISA, immunohistochemistry and TUNEL were used. Some ischemia-reperfusion rats were treated with antiP-selectin mAb. RESULTS Hepatic/ renal function insufficiency, up-regulated expression of P-selectin in plasma and hepatic/renal tissue, hepatic/renal histopathological damages and cell apoptosis were found in rats with hepatic/renal ischemiareperfusion injury, while these changes became less conspicuous in animals treated with anti-P selectin mAb. CONCLUSION P-selectin might mediate neutrophil infiltration and cell apoptosis and contribute to hepatic/renal ischemia-reperfusion injury, anti-P-selectin mAb might be an efficient approach for the prevention and treatment of hepatic/renal ischemia-reperfusion injury.

  13. Effects of 2-APB on Store-operated Ca2+ Channel Currents of Hepatocytes after Hepatic Ischemia/Reperfusion Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    HUANG Changzhou; ZHANG Zongming; QIU Fazu

    2005-01-01

    The effects of hepatic ischemia/reperfusion (I/R) injuries on hepatocellular viability and store-operated calcium current (Isoc) in isolated rat hepatocytes and the effects of 2-APB on storeoperated calcium current (Isoc) in isolated rat hepatocytes after hepaticischemia/reperfusion injuries were studied. Hepatic ischemia and reperfusion injury model was established and whole cell patch-clamp techniques were used to investigate the effects of 2-APB on Isoc. The results showed that ischemia/reperfusion injuries could significantly reduce hepatocellular viability and further increase Isoc in hepatocytes and 2-APB (20, 40, 60, 80, 100 μmol/L) produced a concentration-dependent decrease of Isoc with IC50 value of 64.63±10.56 μmol/L (n= 8). It was concluded that ischemia/reperfusion injuries could reduce hepatocellular viability, probably through increased Isoc in hepatocytes and 2-APB had a protective effect on ischemia/reperfusion-induced liver injury, probably though inhibiting Isoc.

  14. l-Arginine supplementation protects against hepatic ischemia-reperfusion lesions in rabbits.

    Science.gov (United States)

    Taha, M O; Simões, M J; Haddad, M A; Capelato, R C; Budny, N; Matsumoto, A H; Soares, P C M; Santos, W M; Armeato, G D; Araki, C M; Gomes, J S M; Magalhães, K G; Tersariol, I L S; Monteiro, H P; Oliveira-Júnior, I S; Oliveira, I; Jurkiewicz, A; Caricati-Neto, A

    2009-04-01

    We evaluated the effects of a substrate in the biosynthesis of nitric oxide (NO)-l-arginine (LARG)-on hepatic lesions caused by ischemia/reperfusion (I/R) injury in rabbit livers. Rabbits were pretreated with LARG (150 mg/kg IV) or saline solution 0.9% (SS) before the hepatic I/R procedure. The effects of LARG on hepatic injury were evaluated before and after I/R. The warm hepatic I/R procedure produced profound acute liver injury, as indicated by elevated values of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactic dehydrogenase (LDH), as well as a high apoptotic cell count. All changes were attenuated by treatment with LARG before the hepatic I/R procedure. These results suggested that LARG produced protective effects on hepatic I/R lesions. This protective effect of LARG was probably associated with blocking generation of superoxide anions during the hepatic I/R procedure.

  15. Effect of calcitonin gene-related peptide and nerve growth factor on spatial learning and memory abilities of rats following focal cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Guangshun Zheng; Yongjie Yang; Xiubin Fang

    2006-01-01

    BACKGROUND: Calcitonin gene-related peptide (CGRP) and nerve growth actor (NGF) cam improve spatial learning and memory abilities of rats with cerebral ischemia/reperfusion; however, the effect of combination of them on relieving learning and memory injury following cerebral ischemia/reperfusion should be further studied.OBJECTIVE:To study the effects of exogenous CGRP and NGF on learning and memory abilities of rats with focal cerebral ischemia/reperfusion.DESIGN: Randomized controlled animal study.SETTING:Department of Neurosurgery, the Second Hospital of Xiamen; Department of Neurosurgery, the Second Affiliated Hospital of China Medical University; Department of Neurobiology, Basic Medical College of China Medical University.MATERIALS:A total of 30 healthy male SD rats, aged 8 weeks, of clean grade, weighing 250-300 g, were provided by Experimental Animal Department of China Medical University. All rats were randomly divided into sham-operation group, ischemia/reperfusion group and treatment group with 10 in each group. The main reagents were detailed as the follows: 100 g/L chloral hydrate, 0.5 mL CGRP (2 mg/L, Sigma Company, USA),and NGF (1 × 106 U/L, 0.5 mL, Siweite Company, Dalian).METHODS: The experiment was carried out in the Department of Neurobiology, Basic Medical College of China Medical University from February to duly 20055. Rat models of middle cerebral artery occlusion were established by method of occlusion, 2 hours after that rats were anesthetized and the thread was slightly drawn out for 10 mm under direct staring to perform reperfusion. Rats in the ischemia/reperfusion group received intraperitoneal injection of 1 mL saline via the abdomen at two hours later, while rats in the treatment group at 2 hours later received intraperitoneal injection of 2 mg/L CGRP (0.5 mL) and 1 ×106 U/L NGF (0.5 mL) once a day for 10 successive days. First administration was accomplished within 15 minutes after ischemia/reperfusion. Rats in the sham

  16. Effect of lidocaine on retinal aquaporin-4 expression after ischemia/reperfusion injury in the rat

    Institute of Scientific and Technical Information of China (English)

    Liying He; Li Li

    2008-01-01

    BACKGROUND: Several studies have demonstrated that high doses of lidocaine can reduce edema in rats with brain injury by down-regulating aquaporin-4 (AQP4) expression. The hypothesis for the present study is that lidocaine could retinal edema that is associated with AQP4 expression.OBJECTIVE: This study was designed to investigate the interventional effects of lidocaine on retinal AQP4 expression and retinal edema following ischemia/reperfusion injury in the rat.DESIGN, TIME AND SETTING: This study, a randomized, controlled, animal experiment, was performed at the Basic Research Institute, Chongqing Medical University from September 2006 to May 2007.MATERIALS: Seventy-five, healthy, adult, female, Sprague-Dawley rats were included. A total of 50 rats were used to establish a retinal ischemia/reperfusion injury model using an anterior chamber enhancing perfusion unit. Rabbit anti-rat AQP4 antibody was purchased from Santa Cruz Biotechnology, USA.METHODS: All 75 rats were randomly divided into three groups, with 25 rats in each: control, model, and lidocaine. At each time point (1, 6, 12, 24, and 48 hours after modeling, five rats for each time point), each rat in the lidocaine group was intraperitoneally administered lidocaine with an initial dose of 30 mg/kg, followed by subsequent doses of 15 mg/kg every six hours. The entire treatment process lasted three days for each rat. At each above-mentioned time point, rats in the model group were modeled, but not administered any substances. Rats in the control group received the same treatments as in the lidocaine group except that lidocaine was replaceld by physiological saline.MAIN OUTCOME MEASURES: Following hematoxylin-eosin staining, rat retinal tissue was observed to investigate retinal edema degree through the use of an optical microscope and transmission electron microscope. Retinal AQP4 expression was determined by immunohistochemistry.RESULTS: At each above-mentioned time point, AQP4 expression was

  17. Efecto protector de la melatonina y del tratamiento tópico con la mezcla eutéctica de lidocaína y prilocaína en un modelo de isquemia reperfusión en el colgajo cutáneo microvascularizado en ratas Protective effect of melatonin and the lidocaine and prilocaine eutectic mixture in an ischemia reperfusion injury model in the microvascular cutaneous flap in rats

    Directory of Open Access Journals (Sweden)

    C. Casado Sánchez

    2012-09-01

    Full Text Available El síndrome de isquemia reperfusión es el conjunto de sucesos desarrollados desde la instauración de la isquemia en un tejido hasta su posterior reperfusión. Se trata de una condición limitante y, hasta la fecha, inevitable, en toda cirugía que implique una revascularización tisular. En un intento por buscar medidas terapéuticas frente al estrés oxidativo desarrollado durante este síndrome en los colgajos microvascularizados, se valoró la acción del antioxidante melatonina y de los anestésicos locales lidocaína y prilocaína en un modelo de isquemia reperfusión en el colgajo epigástrico microvascularizado en ratas. Tanto el indol como los fármacos vasoactivos poseen un efecto protector en el tratamiento del síndrome de isquemia reperfusión, desde un punto de vista bioquímico e histológico, destacando su acción sinérgica manifestada principalmente como un incremento en la neovascularización tisular.Ischemia-reperfusion injury is a set of events developed since the introduction of ischemia in a tissue to subsequent reperfusion. It is a limiting condition and, to date, inevitable in any surgery involving tissue revascularization. In an attempt to find therapeutic measures against oxidative stress developed during this syndrome in microvascular flaps, we evaluated the antioxidant action of melatonin and local anesthetics lidocaine and prilocaine in a model of ischemia reperfusion in the microvascularized epigastric flap in rats. The indole and vasoactive drugs have a protective effect in the treatment of ischemia reperfusion injury, from both a biochemical and histological view, emphasizing their synergistic action mainly manifested as an increase in tissue neovascularization.

  18. Effect of intestinal ischemia/reperfusion injury on leptin and orexin-A levels

    Institute of Scientific and Technical Information of China (English)

    LIN Ji; YAN Guangtao; GAO Xiaoning; LIAO Jie; HAO Xiuhua; ZHANG Kai

    2007-01-01

    The aim of this paper is to explore the effect of intestinal ischemia/reperfusion (I/R) injury on leptin and orexin-A levels in peripheral blood and central secretory tissues,and to examine the roles of leptin and orexin-A in acute inflammatory responses.An intestinal I/R injury model of rats was made;the rats were grouped according to the time of after 60 rnin ischemia.Radioimmunoassay was employed to detect the levels of leptin in serum and adipose tissue and orexin-A levels in plasma and hypothalamus.Reverse transcriptase-polymerase chain reaction was used to detect mRNA expressions of adipose leptin and hypothalamus orexin-A.Compared with the levels before the injury,serum leptin in 60 rain ischemia/30 rain reperfusion (I60'R30) group decreased and that of I60'R360' group increased.Compared with sham-operation group (sham group) after injury,serum leptin level of I60aq360' group increased,adipose leptin levels of I60'R30' and I60'R90' decreased,and adipose leptin in I60'R360' group increased.After the injury,adipose leptin mRNA expressions of I60'30',I60'R240' and I60'R360' increased,whereas that of I60'R150' group decreased as compared with the sham group.There was no significant difference in the protein levels of orexin-A,either between plasma and hypothalamus or between pro- and post-I/R injury.Compared with sham group,hypothalamus orexin-A mRNA expressions of I60'R30' and I60'90'decreased gradually after the injury,with that of I60'R150'group reaching the lowest,and those of I60'R240' andI60'R360' recovering gradually,although they were still significantly lower than that of sham group.Leptin and orexin-A respond to intestinal I/R injury in a time-dependent manner,with leptin responding more quickly than orexin-A does,and both of them may contribute to the metabolic disorders in acute inflammation.

  19. Uric Acid Is Protective After Cerebral Ischemia/Reperfusion in Hyperglycemic Mice.

    Science.gov (United States)

    Justicia, Carles; Salas-Perdomo, Angélica; Pérez-de-Puig, Isabel; Deddens, Lisette H; van Tilborg, Geralda A F; Castellví, Clara; Dijkhuizen, Rick M; Chamorro, Ángel; Planas, Anna M

    2016-12-15

    Hyperglycemia at stroke onset is associated with poor long-term clinical outcome in numerous studies. Hyperglycemia induces intracellular acidosis, lipid peroxidation, and peroxynitrite production resulting in the generation of oxidative and nitrosative stress in the ischemic tissue. Here, we studied the effects of acute hyperglycemia on in vivo intercellular adhesion molecule-1 (ICAM-1) expression, neutrophil recruitment, and brain damage after ischemia/reperfusion in mice and tested whether the natural antioxidant uric acid was protective. Hyperglycemia was induced by i.p. administration of dextrose 45 min before transient occlusion of the middle cerebral artery. Magnetic resonance imaging (MRI) was performed at 24 h to measure lesion volume. A group of normoglycemic and hyperglycemic mice received an i.v. injection of micron-sized particles of iron oxide (MPIOs), conjugated with either anti-ICAM-1 antibody or control IgG, followed by T2*w MRI. Neutrophil infiltration was studied by immunofluorescence and flow cytometry. A group of hyperglycemic mice received an i.v. infusion of uric acid (16 mg/kg) or the vehicle starting after 45 min of reperfusion. ICAM-1-targeted MPIOs induced significantly larger MRI contrast-enhancing effects in the ischemic brain of hyperglycemic mice, which also showed more infiltrating neutrophils and larger lesions than normoglycemic mice. Uric acid reduced infarct volume in hyperglycemic mice but it did not prevent vascular ICAM-1 upregulation and did not significantly reduce the number of neutrophils in the ischemic brain tissue. In conclusion, hyperglycemia enhances stroke-induced vascular ICAM-1 and neutrophil infiltration and exacerbates the brain lesion. Uric acid reduces the lesion size after ischemia/reperfusion in hyperglycemic mice.

  20. Ligustrazine monomer against cerebral ischemia-reperfusion injury

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    Hai-jun Gao

    2015-01-01

    Full Text Available Ligustrazine (2,3,5,6-tetramethylpyrazine is a major active ingredient of the Szechwan lovage rhizome and is extensively used in treatment of ischemic cerebrovascular disease. The mechanism of action of ligustrazine use against ischemic cerebrovascular diseases remains unclear at present. This study summarizes its protective effect, the optimum time window of administration, and the most effective mode of administration for clinical treatment of cerebral ischemia/reperfusion injury. We examine the effects of ligustrazine on suppressing excitatory amino acid release, promoting migration, differentiation and proliferation of endogenous neural stem cells. We also looked at its effects on angiogenesis and how it inhibits thrombosis, the inflammatory response, and apoptosis after cerebral ischemia. We consider that ligustrazine gives noticeable protection from cerebral ischemia/reperfusion injury. The time window of ligustrazine administration is limited. The protective effect and time window of a series of derivative monomers of ligustrazine such as 2-[(1,1-dimethylethyloxidoimino]methyl]-3,5,6-trimethylpyrazine, CXC137 and CXC195 after cerebral ischemia were better than ligustrazine.

  1. Intestinal microflora in rats with ischemia/reperfusion liver injury

    Institute of Scientific and Technical Information of China (English)

    XING Hui-chun; LI Lan-juan; XU Kai-jin; SHEN Tian; CHEN Yun-bo; SHENG Ji-fang; YU Yun-song; CHEN Ya-gang

    2005-01-01

    Objectives: To investigate the intestinal microflora status related to ischemia/reperfusion (I/R) liver injury and explore the possible mechanism. Methods: Specific pathogen free grade Sprague-Dawley rats were randomized into three groups: Control group (n=8), sham group (n=6) and I/R group (n=10). Rats in the control group did not receive any treatment, rats in the I/R group were subjected to 20 min of liver ischemia, and rats in the sham group were only subjected to sham operation. Twenty-two hours later, the rats were sacrificed and liver enzymes and malondialdehyde (MDA), superoxide dismutase (SOD), serum endotoxin,intestinal bacterial counts, intestinal mucosal histology, bacterial translocation to mesenteric lymph nodes, liver, spleen, and kidney were studied. Results: Ischemia/reperfusion increased liver enzymes, MDA, decreased SOD, and was associated with plasma endotoxin elevation in the I/R group campared to those in the sham group. Intestinal Bifidobacteria and Lactobacilli decreased and intestinal Enterobacterium and Enterococcus, bacterial translocation to kidney increased in the I/R group compared to the sham group. Intestinal microvilli were lost, disrupted and the interspace between cells became wider in the I/R group.Conclusion: I/R liver injury may lead to disturbance of intestinal microflora and impairment of intestinal mucosal barrier function,which contributes to endotoxemia and bacterial translocation to kidney.

  2. Mitochondria-Targeted Antioxidants: Future Perspectives in Kidney Ischemia Reperfusion Injury

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    Aleksandra Kezic

    2016-01-01

    Full Text Available Kidney ischemia/reperfusion injury emerges in various clinical settings as a great problem complicating the course and outcome. Ischemia/reperfusion injury is still an unsolved puzzle with a great diversity of investigational approaches, putting the focus on oxidative stress and mitochondria. Mitochondria are both sources and targets of ROS. They participate in initiation and progression of kidney ischemia/reperfusion injury linking oxidative stress, inflammation, and cell death. The dependence of kidney proximal tubule cells on oxidative mitochondrial metabolism makes them particularly prone to harmful effects of mitochondrial damage. The administration of antioxidants has been used as a way to prevent and treat kidney ischemia/reperfusion injury for a long time. Recently a new method based on mitochondria-targeted antioxidants has become the focus of interest. Here we review the current status of results achieved in numerous studies investigating these novel compounds in ischemia/reperfusion injury which specifically target mitochondria such as MitoQ, Szeto-Schiller (SS peptides (Bendavia, SkQ1 and SkQR1, and superoxide dismutase mimics. Based on the favorable results obtained in the studies that have examined myocardial ischemia/reperfusion injury, ongoing clinical trials investigate the efficacy of some novel therapeutics in preventing myocardial infarct. This also implies future strategies in preventing kidney ischemia/reperfusion injury.

  3. Effect of ONO-4057 and tacrolimus on ischemia-reperfusion injury of the liver

    Institute of Scientific and Technical Information of China (English)

    Takayuki Takeichi; Shinji Uemoto; Sachiko Minamiguchi; Izumi Takeyoshi; Yukihiro Inomata; Koichi Tanaka; Eiji Kobayashi

    2009-01-01

    AIM: To investigate the effects of a novel Leukotriene B4 receptor antagonist and/or tacrolimus on ischemiareperfusion in a rat liver model.METHODS: Male Lewis rats were pretreated with ONO-4057 (100 mg/kg) and/or tacrolimus (1 mg/kg) orally, and divided into four experimental groups; group 1 (control), group 2 (ONO-4057), group 3 (tacrolimus),group 4 (ONO-4057 + tacrolimus).RESULTS: There was a tendency for long survival in the groups treated with tacrolimus alone and ONO-4057 plus tacrolimus. Post-reperfusion serum aspartate aminotransferase levels decreased more significantly in ONO-4057 plus tacrolimus group ( P < 0.01), than in the tacrolimus alone group ( P < 0.05), compared to controls. CONCLUSION: This study demonstrated that pretreatment with ONO-4057 in combination with tacrolimus produced additive effects in a rat model of liver ischemia- reperfusion injury.

  4. DNA damage response in renal ischemia-reperfusion and ATP-depletion injury of renal tubular cells.

    Science.gov (United States)

    Ma, Zhengwei; Wei, Qingqing; Dong, Guie; Huo, Yuqing; Dong, Zheng

    2014-07-01

    Renal ischemia-reperfusion leads to acute kidney injury (AKI) that is characterized pathologically by tubular damage and cell death, followed by tubular repair, atrophy and interstitial fibrosis. Recent work suggested the possible presence of DNA damage response (DDR) in AKI. However, the evidence is sketchy and the role and regulation of DDR in ischemic AKI remain elusive. In this study, we demonstrated the induction of phosphorylation of ATM, H2AX, Chk2 and p53 during renal ischemia-reperfusion in mice, suggesting DDR in kidney tissues. DDR was also induced in vitro during the recovery or "reperfusion" of renal proximal tubular cells (RPTCs) after ATP depletion. DDR in RPTCs was abrogated by supplying glucose to maintain ATP via glycolysis, indicating that the DDR depends on ATP depletion. The DDR was also suppressed by the general caspase inhibitor z-VAD and the overexpression of Bcl-2, supporting a role of apoptosis-associated DNA damage in the DDR. N-acetylcysteine (NAC), an antioxidant, suppressed the phosphorylation of ATM and p53 and, to a less extent, Chk2, but NAC increased the phosphorylation and nuclear foci formation of H2AX. Interestingly, NAC increased apoptosis, which may account for the observed H2AX activation. Ku55933, an ATM inhibitor, blocked ATM phosphorylation and ameliorated the phosphorylation of Chk2 and p53, but it increased H2AX phosphorylation and nuclear foci formation. Ku55933 also increased apoptosis in RPTCs following ATP depletion. The results suggest that DDR occurs during renal ischemia-reperfusion in vivo and ATP-depletion injury in vitro. The DDR is partially induced by apoptosis and oxidative stress-related DNA damage. ATM, as a sensor in the DDR, may play a cytoprotective role against tubular cell injury and death.

  5. Ultrastructural changes of rat cortical neurons following ligustrazine intervention for cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Hui Zhang; Jianfeng Dong; Qiuzhen Zhao; Wen Song; Aihua Bo

    2008-01-01

    BACKGROUND: Ligustrazine can reduce the production of free radicals and the content of malonaldehyde, and improve the enzymatic activity of adenosine-triphosphate in cerebral anoxia. It also can increase the expression of heat shock protein-70 and Bcl-2, thus alleviating brain tissue injury caused by cerebral ischemia/reperfusion. This study aimed to address the question of whether ligustrazine can protect the membrane structure of neurons.OBJECTIVE: To establish rat models of cerebral ischemia/reperfusion, observe the membrane structure and main organelles of neurons with electron microscope after ligustrazine intervention, and to analyze the dose-dependent effects of ligustrazine on neuronal changes.DESIGN: Arandomized controlled study.SETTING: Department of Anatomy Research and Electron Microscopy, Hebei North University. MATERIALS: Forty Wistar rats of SPS grade, weighing 180–250 g and equal proportion of female and male, were provided by Hebei Medical University Animal Center (No. 060126). The ligustrazine injection (40 g/L, No. 05012) was produced by Beijing Yongkang Yaoye. LKB4 Ultramicrotome was purchased from LKB Company in Sweden. JEM100CXII electron microscope was purchased from JEOL in Japan.METHODS: The experiment was performed in the Laboratory of the Department of Anatomy and Electron Microscopy, Hebei North University from June to August 2006. ① Wistar rats were allowed to adapt for 3 days, and were then randomly divided into four groups, according to the numeration table method: normal group, model group, low-dose ligustrazine group, and high-dose ligustrazine group. There were 10 rats in each group. ②Rats in the model group, low-dose ligustrazine group, and high-dose ligustrazine group un-derwent cerebral ischemia/reperfusion model, according to Bannister's method. The carotid artery was opened for reperfusion after 90 minutes of cerebral ischemia. Samples were collected from the cerebral cor-tex after 24 hours. Animals from the ligustrazine

  6. Matrix metalloproteinase-9: A deleterious link between hepatic ischemia-reperfusion and colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Sébastien Lenglet; Fran(c)ois Mach; Fabrizio Montecucco

    2012-01-01

    Despite the advent of improved surgical techniques and the development of cytotoxic chemotherapeutic agents useful for the treatment of colorectal cancer,the primary clinical challenge remains that of preventing and combating metastatic spread.Surgical resection is the best treatment for colorectal metastases isolated to the liver.However,in rodent models,the hepatic ischemia-reperfusion (I/R) applied during the surgery accelerates the outgrowth of implanted tumors.Among the adverse effects of I/R on cellular function,several studies have demonstrated an over expression of the matrix metalloproteinase-9 (MMP-9) in the ischemic liver.Since several studies showed high local levels of expression and activity of this proteolytic enzyme in the primary colorectal adenocarcinoma,the role of MMP-9 might be considered as a potential common mediator,favoring both growth of local tumor and the dissemination of colorectal carcinoma metastases.

  7. The protective effect of calcitonin gene-related peptide on gastric mucosa injury after cerebral ischemia reperfusion in rats%大鼠脑缺血再灌注后降钙素基因相关肽对受损胃黏膜的保护作用

    Institute of Scientific and Technical Information of China (English)

    冯国营; 许晓博; 王迁

    2009-01-01

    @@ The purpose of the present study is to investigate the protective effect of calcitonin gene-related pepfide (CGRP) on gastric mucosa injury after focal cerebral ischemia reperfusion and gastric ischemia-reperfusion in rats. Wistar male rats (280-320g) were selected for this experiment. Focal cerebral ischemia and reperfusion rat model was established with left middle cerebral artery occlusion by using thread inserting.

  8. X-ray phase-contrast tomography of renal ischemia-reperfusion damage.

    Directory of Open Access Journals (Sweden)

    Astrid Velroyen

    Full Text Available The aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation.The effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV. To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 µm. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed.GB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94. Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders.In conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney.

  9. Protective Effects of L-Malate against Myocardial Ischemia/Reperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Shiao Ding

    2016-01-01

    Full Text Available Objective. To investigate the protective effects of L-malate against myocardial ischemia/reperfusion (I/R injury in rats. Methods. Male Sprague-Dawley rats were randomly assigned to the following groups: sham (sham, an ischemia/reperfusion (I/R model group (model, an DMF pretreated group (DMF, and 5 L-malate pretreated groups (15, 60, 120, 240, or 480 mg/kg, gavage before inducing myocardial ischemia. Plasma LDH, cTn-I, TNF-α, hs-CRP, SOD, and GSH-PX were measured 3 h later I/R. Areas of myocardial infarction were measured; hemodynamic parameters during I/R were recorded. Hearts were harvested and Western blot was used to quantify Nrf2, Keap1, HO-1, and NQO-1 expression in the myocardium. Results. L-malate significantly reduced LDH and cTn-I release, reduced myocardial infarct size, inhibited expression of inflammatory cytokines, and partially preserved heart function, as well as increasing antioxidant activity after myocardial I/R injury. Western blot confirmed that L-malate reduced Kelch-like ECH-associated protein 1 in ischemic myocardial tissue, upregulated expression of Nrf2 and Nrf2 nuclear translocation, and increased expression of heme oxygenase-1 and NAD(PH:quinone oxidoreductase 1, which are major targets of Nrf2. Conclusions. L-malate may protect against myocardial I/R injury in rats and this may be associated with activation of the Nrf2/Keap1 antioxidant pathway.

  10. Effects of phycocyanin on apoptosis and expression of superoxide dismutase in cerebral ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Meizeng Zhang; Lihua Wang; Yunliang Guo

    2006-01-01

    BACKGROUND: The application of exogenous antioxidant is always the focus in the prevention and treatment of cerebral ischemia. Phycocyanin has the effects against oxidation and inflammation, but its role in the pathophysiological process of cerebral ischemia reperfusion injury still needs further investigation.OBJECTIVE: To observe the effects of phycocyanin on the expression of superoxide dismutase (SOD),apoptosis and form of the nerve cells in rats after cerebral ischemia reperfusion injury.DESIGN: A randomized control animal experiment.SETTING: Institute of Cerebrovascular Disease, Medical School Hospital of Qingdao University.MATERIALS: Fifty-two healthy adult male Wistar rats of clean degree, weighing 220-260 g, were used. Phycocyanin was provided by the Institute of Oceanology, Chinese Academy of Sciences.METHODS: The experiments were carried out in Shangdong Key Laboratory for Prevention and Treatment of Brain Diseases from May to December 2005. ① All the rats were divided into three groups according to the method of random number table: sham-operated group (n=4), control group (n=24) and treatment group (n=24). Models of middle cerebral artery occlusion/reperfusion (MCAO/R) were established by the introduction of thread through external and internal carotid arteries in the control group and treatment group. After 1-hour ischemia and 2-hour reperfusion, rats in the treatment group were administrated with gastric perfusion of phycocyanin suspension (0.1 mg/g), and those in the control group were given saline of the same volume, and no treatment was given to the rats in the sham-operated group. ②The samples were removed and observed at ischemia for 1 hour and reperfusion for 6 and 12 hours and 1, 3, 7 and 14 days respectively in the control group and treatment group, 4 rats for each time point, and those were removed at 1 day postoperatively in the sham-operated group. Forms of the nerve cells were observed with toluidine blue staining. Apoptosis after

  11. Effect of hyperbaric oxygen preconditioning on expression of neuroplasticity after acute global cerebral ischemia-reperfusion in aged rats%高压氧预处理对老龄大鼠全脑缺血再灌注损伤后神经可塑性的影响

    Institute of Scientific and Technical Information of China (English)

    邹磊; 刘丹彦; 殷薇; 宋云

    2014-01-01

    Objective To investigate the effect of hyperbaric oxygen preconditioning (HOP)on expression of Nogo mRNA,No-go-A and Ng R protein in the cerebral cortex after acute global cerebral ischemia-reperfusion (I/R)in aged rats and to study its mechanism affecting neuroplasticity.Methods Forty-two aged male SD rats were randomly divided into 4 groups:control group (C group,n=6),hyperbaric oxygen group (H group,n=12),cerebral I/R injury group (I/R group,n=12)and HOP group (n=12). The H group and the HOP group were placed in the hyperbaric oxygen cabin for 1 h per day with a oxygen pressure of 0.2 Mpa for successive 5 d,at 24 h after last time of hyperbaric oxygen preconditioning the I/R group and the HOP group adopted the modified Pulsinelli vessel occlusion method for preparing the rat I/R injury model,with global cerebral ischemia for 10 min and reperfusion for 24 h,each 6 rats were randomly taken from the the H group,I/R group and HOP group and their heads were cut off for taking the brain and isolating the cerebral cortex.The real time fluorescence quantification PCR was adopted to detect the expression level of Nogo mRNA and the Nogo-A protein level was detected by Western blot.The rats in various groups were performed the T1 WI and T2WI scanning in the transection position and the coronal positions.Results There were no obvious ischemic brain infarction in the normal control group and the H group,the arc-shaped bilateral cortex ischemic infarct area was clearly seen in the ischemic group,the ischemic infarct area was also seen in the HOP ischemia group,but its area was smaller than which in the ischemic group.Compared with the C group,the expression of Nogo mRNA and the Nogo-A protein in the HOP group was up-regulated(P<0.05);compared with the I/R group,the expression of Nogo mRNA and the Nogo-A protein was down-regulated(P<0.05). Conclusion HOP increases the neuroplasticity and can reduce the cerebral ischemic infarction area in the exceed acute stage of rat acute

  12. PROTECTIVE EFFECTS OF ERYTHROPOIETIN ON MYO-CARDIUM AGAINST ISCHEMIA-REPERFUSION INJURY

    Institute of Scientific and Technical Information of China (English)

    YANG Di-cheng; XIAO Ming-di; LU Cheng-bao; LV Zhi-qian; DUAN Liang

    2008-01-01

    Objective To explore the protective effects of erythropoietin (EPO) on myocardium against ischemia-reperfusion injury (IRI). Methods The Langendorff model of isolated rat heart was set up and a 3-stage protocol was performed: 20 min stabilization, 30 min global ischemia, and 120 min reperfusion. Sixty SD rats were randomly divided into sham group, ischemia-reperfusion group (I/R group ) and EPO treated group (EPO group). Heart rate (HR), left ventricular developed pressure (LVDP), the first derivative (△dp/dt max) and coronary flow (CF) were recorded at the 20th minute of stabilization and the 120th minute of reperfusion. Lactate dehydrogenase (LDH) and creatine phosphokinase (CK) in the coronary effluent at the 60th minute of reperfusion, the levels of myocardial nuclear factor-kappa B (NF-KB) and the myocardial content of tumor necrosis factor-α (TNF-α) ,interleukin-1β (IL-1β) were measured at the end of reperfusion. Results No statistically significant differences were observed on the aspect of hemodynamic parameters among the groups at the 20th minute of stabilization, but at the 120th minute of reperfusion, the recovery ratio of EPO group was higher than I/R group (P<0.05). LDH and CK in the coronary effluent, the levels of myocardial NF-κB and TNF-α,IL-1β expression in EPO group were significantly lower than those in I/R group, but higher than sham group (P<0.05). Conclusion EPO has protective effects on myocardium against IRI possibly through the mechanism of relieving the myocardial inflammatory reaction by regulating the activation of NF-κB and then decreasing the expression of proinflammatory factors TNF-α and IL-1β.

  13. Differential effects of heptanoate and hexanoate on myocardial citric acid cycle intermediates following ischemia-reperfusion.

    Science.gov (United States)

    Okere, Isidore C; McElfresh, Tracy A; Brunengraber, Daniel Z; Martini, Wenjun; Sterk, Joseph P; Huang, Hazel; Chandler, Margaret P; Brunengraber, Henri; Stanley, William C

    2006-01-01

    In the normal heart, there is loss of citric acid cycle (CAC) intermediates that is matched by the entry of intermediates from outside the cycle, a process termed anaplerosis. Previous in vitro studies suggest that supplementation with anaplerotic substrates improves cardiac function during myocardial ischemia and/or reperfusion. The present investigation assessed whether treatment with the anaplerotic medium-chain fatty acid heptanoate improves contractile function during ischemia and reperfusion. The left anterior descending coronary artery of anesthetized pigs was subjected to 60 min of 60% flow reduction and 30 min of reperfusion. Three treatment groups were studied: saline control, heptanoate (0.4 mM), or hexanoate as a negative control (0.4 mM). Treatment was initiated after 30 min of ischemia and continued through reperfusion. Myocardial CAC intermediate content was not affected by ischemia-reperfusion; however, treatment with heptanoate resulted in a more than twofold increase in fumarate and malate, with no change in citrate and succinate, while treatment with hexanoate did not increase fumarate or malate but increased succinate by 1.8-fold. There were no differences among groups in lactate exchange, glucose oxidation, oxygen consumption, and contractile power. In conclusion, despite a significant increase in the content of carbon-4 CAC intermediates, treatment with heptanoate did not result in improved mechanical function of the heart in this model of reversible ischemia-reperfusion. This suggests that reduced anaplerosis and CAC dysfunction do not play a major role in contractile and metabolic derangements observed with a 60% decrease in coronary flow followed by reperfusion.

  14. Effects of ligustrazine on somatosensory evoked potential in normal rabbits and rabbits with cerebral ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Deshan Liu; Shuli Wang; Yuanyuan Hao

    2006-01-01

    BACKGROUND: Somatosensory evoked potential (SEP) has become a method with higher sensitivity and specificity than electroencephalogram in detecting the brain function and the region, range and degree of ischemia. However, the effects of ligustrazine on SEP is still not clear.OBJECTIVE: To study the protective effects of ligustrazini injection on cerebral ischemia-reperfusion injury.DESIGN: Auto-control study, random grouping.SETTING: Qilu Hospital of Shandong University.MATERIALS: The experiment was completed in the Cerebral Functional Room of Qilu Hospital Affiliated to Shandong University from March 2002 to June 2004. A totally of 24 healthy Harbin rabbits were randomly divided into blank control group (n=8), model control group (n=8) and ligustrazine treatment group (n=8).Hydrochloric ligustrazine injection, 40 mg/2 mL each ampoule, was provided by the Third Pharmaceutical Factory of Beijing (certification: 93035236273). The main component was hydrochloric ligustrazine and the chemical name was 2, 3, 5, 6-tetramethyl pyrazine hydrochloride.METHODS: ① Modeling method: The bilateral common carotid artery ligation was adopted to make the model. ② Index of cerebral functional lesion evaluated with SEP during ischemia-reperfusion: DISA 2000C neuromyoeletrometer provided by Dantec Electronics Ltd, Denmark was used to detect SEP. ③ Interventional process: Blank control group: The latencies and amplitudes of SEP were measured before injection with 1.5 mg/kg ligustrazine and at the points of 15 minutes, 20 minutes, 30 minutes, 60 minutes, 90 minutes and 120 minutes after injection. Ligustrazine treatment group: Rabbits were injected with 1.5 mg/kg ligustrazine, and those of model control group were injected the same volume of saline. Thirty minutes later, the bilateral common carotid artery of the rabbits all had been ligated for 30 minutes, and then reperfused for 120 minutes. The latencies and amplitudes of SEP were measured before injection, before ligation, at

  15. Pyruvate dehydrogenase complex in cerebral ischemia-reperfusion injury

    Directory of Open Access Journals (Sweden)

    Alexa Thibodeau

    2016-01-01

    Full Text Available Pyruvate dehydrogenase (PDH complex is a mitochondrial matrix enzyme that serves a critical role in the conversion of anaerobic to aerobic cerebral energy. The regulatory complexity of PDH, coupled with its significant influence in brain metabolism, underscores its susceptibility to, and significance in, ischemia-reperfusion injury. Here, we evaluate proposed mechanisms of PDH-mediated neurodysfunction in stroke, including oxidative stress, altered regulatory enzymatic control, and loss of PDH activity. We also describe the neuroprotective influence of antioxidants, dichloroacetate, acetyl-L-carnitine, and combined therapy with ethanol and normobaric oxygen, explained in relation to PDH modulation. Our review highlights the significance of PDH impairment in stroke injury through an understanding of the mechanisms by which it is modulated, as well as an exploration of neuroprotective strategies available to limit its impairment.

  16. Functionally Selective AT(1) Receptor Activation Reduces Ischemia Reperfusion Injury

    DEFF Research Database (Denmark)

    Hostrup, Anders; Christensen, Gitte Lund; Bentzen, Bo Hjort;

    2012-01-01

    of the physiological functions of AngII. The AT(1)R mediates its effects through both G protein-dependent and independent signaling, which can be separated by functionally selective agonists. In the present study we investigate the effect of AngII and the ß-arrestin biased agonist [SII]AngII on ischemia......-reperfusion injury in rat hearts. Isolated hearts mounted in a Langendorff perfused rat heart preparations showed that preconditioning with [SII]AngII reduced the infarct size induced by global ischemia from 46±8.4% to 22±3.4%. In contrast, neither preconditioning with AngII nor postconditioning with AngII or [SII...

  17. Alternative Interventions to Prevent Oxidative Damage following Ischemia/Reperfusion

    Directory of Open Access Journals (Sweden)

    Simón Quetzalcoatl Rodríguez-Lara

    2016-01-01

    Full Text Available Ischemia/reperfusion (I/R lesions are a phenomenon that occurs in multiple pathological states and results in a series of events that end in irreparable damage that severely affects the recovery and health of patients. The principal therapeutic approaches include preconditioning, postconditioning, and remote ischemic preconditioning, which when used separately do not have a great impact on patient mortality or prognosis. Oxidative stress is known to contribute to the damage caused by I/R; however, there are no pharmacological approaches to limit or prevent this. Here, we explain the relationship between I/R and the oxidative stress process and describe some pharmacological options that may target oxidative stress-states.

  18. Alternative Interventions to Prevent Oxidative Damage following Ischemia/Reperfusion

    Science.gov (United States)

    Rodríguez-Lara, Simón Quetzalcoatl; Ramírez-Lizardo, Ernesto Javier; Totsuka-Sutto, Sylvia Elena; Castillo-Romero, Araceli; García-Cobián, Teresa Arcelia

    2016-01-01

    Ischemia/reperfusion (I/R) lesions are a phenomenon that occurs in multiple pathological states and results in a series of events that end in irreparable damage that severely affects the recovery and health of patients. The principal therapeutic approaches include preconditioning, postconditioning, and remote ischemic preconditioning, which when used separately do not have a great impact on patient mortality or prognosis. Oxidative stress is known to contribute to the damage caused by I/R; however, there are no pharmacological approaches to limit or prevent this. Here, we explain the relationship between I/R and the oxidative stress process and describe some pharmacological options that may target oxidative stress-states. PMID:28116037

  19. Passive targeting of lipid-based nanoparticles to mouse cardiac ischemia-reperfusion injury

    NARCIS (Netherlands)

    Geelen, T.; Paulis, L.E.M.; Coolen, B.F.; Nicolay, K.; Strijkers, G.J.

    2013-01-01

    Reperfusion therapy is commonly applied after a myocardial infarction. Reperfusion, however, causes secondary damage. An emerging approach for treatment of ischemia-reperfusion (IR) injury involves the delivery of therapeutic nanoparticles to the myocardium to promote cell survival and constructivel

  20. MicroRNAs regulate mitochondrial apoptotic pathway in myocardial ischemia-reperfusion-injury.

    Science.gov (United States)

    Makhdoumi, Pouran; Roohbakhsh, Ali; Karimi, Gholamreza

    2016-12-01

    MicroRNAs (miRNAs) are small non-coding RNAs that act as post-transcriptional gene regulators. They are involved in the pathogenesis of different disorders including heart diseases. MiRNAs contribute to ischemia/reperfusion injury (I/RI) by altering numerous key signaling elements. Together with alterations in the various potential signaling pathways, modification in miRNA expression has been suggested as a part of the response network following ischemia/reperfusion (I/R). In addition, cardiac mitochondrial homeostasis is closely associated with cardiac function and impairment of mitochondrial activity occurred after ischemia/reperfusion injury. MiRNAs play a key role in the regulation of mitochondrial apoptotic pathway and signaling proteins. In this review, we summarize the knowledge currently available regarding the molecular mechanisms of miRNA-regulated mitochondrial functions during ischemia/reperfusion injury. This regulation occurs in different stages of mitochondrial apoptosis pathway.

  1. The pathways by which mild hypothermia inhibits neuronal apoptosis following ischemia/reperfusion injur y

    Institute of Scientific and Technical Information of China (English)

    Chun Luo; Su-yue Pan

    2015-01-01

    Several studies have demonstrated that mild hypothermia exhibits a neuroprotective role and it can inhibit endothelial cell apoptosis following ischemia/reperfusion injury by decreasing casp-ase-3 expression. It is hypothesized that mild hypothermia exhibits neuroprotective effects on neurons exposed to ischemia/reperfusion condition produced by oxygen-glucose deprivation. Mild hypothermia signiifcantly reduced the number of apoptotic neurons, decreased the expres-sion of pro-apoptotic protein Bax and increased mitochondrial membrane potential, with the peak of anti-apoptotic effect appearing between 6 and 12 hours after the injury. These ifndings indicate that mild hypothermia inhibits neuronal apoptosis following ischemia/reperfusion injury by protecting the mitochondria and that the effective time window is 6–12 hours after ischemia/reperfusion injury.

  2. The pathways by which mild hypothermia inhibits neuronal apoptosis following ischemia/reperfusion injury

    Directory of Open Access Journals (Sweden)

    Chun Luo

    2015-01-01

    Full Text Available Several studies have demonstrated that mild hypothermia exhibits a neuroprotective role and it can inhibit endothelial cell apoptosis following ischemia/reperfusion injury by decreasing casp-ase-3 expression. It is hypothesized that mild hypothermia exhibits neuroprotective effects on neurons exposed to ischemia/reperfusion condition produced by oxygen-glucose deprivation. Mild hypothermia significantly reduced the number of apoptotic neurons, decreased the expression of pro-apoptotic protein Bax and increased mitochondrial membrane potential, with the peak of anti-apoptotic effect appearing between 6 and 12 hours after the injury. These findings indicate that mild hypothermia inhibits neuronal apoptosis following ischemia/reperfusion injury by protecting the mitochondria and that the effective time window is 6-12 hours after ischemia/reperfusion injury

  3. Effects of systemic domestic recombinant human erythropoietin on HIF-1α expression in the retina in a rabbit model of acute high intraocular pressure

    Institute of Scientific and Technical Information of China (English)

    Yan-ping Song; Jian-ming Wang; Mei Zhang; Na Hui; Shi-ping Zhao; Kai Hu

    2009-01-01

    Objective To observe the expression of hypoxia inducible faetor-1α (HIF-1α) in the retina of rabbits with acute high intraocular pressure and to investigate the mechanism of systemic domestic recombinant human erythropoietin (rhEPO) protecting the retina from ischemia-reperfusion injury. Methods First, control group and model group were established in rabbit eyes. The acute high intraocular pressure model was established by saline perfusion into anterior chamber, and then hypodermic injection of domestic rhEPO was made. HIF-1α protein in the retina was observed by immunohistochemical staining method on days 1, 3, 7 and 14 after retinal ischemla-reperfusion, respectively. Results No cells with HIF-la positive expression were observed in the retina of the control group. Ceils with HIF-1α positive expression in the model group outnumbered those in the control group (P < 0. 01). The resemblance pattern occurred in EPO group but its degree was slightly greater than that in the model group from day 3 after ischemia-reperfusion (P<0.05). Conclusion Domestic rhEPO can down-regulate the expression of HIF-1α in the retina with acute high intraocular pressure, which may be one of the mechanisms that rhEPO protects the retina from ischemia-reperfusion injury.

  4. Ketamine anesthesia reduces intestinal ischemia/reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Carlos Roddgo Cámara; Francisco Javier Guzmán; Ernesto Alexis Barrera; Andrés Jesús Cabello; Armando Garcia; Nancy Esthela Fernández; Eloy Caballero; Jesus Ancer

    2008-01-01

    AIM:To investigate the effects of ketamine anesthesia on the motility alterations and tissue injury caused by ischemia/reperfusion in rats.METHODS:Thirty maIe Wistar rats weighing 200-250 g were used.Ischemia was induced by obstructing blood flow in 25% of the total small intestinal length(ileum)with a vascular clamp for 45 min,after which either 60 min or 24 h of reperfusion was allowed.Rats were either anesthetized with pento-barbital sodium(50 mg/kg)or ketamine(100 mg/kg).Control groups received sham surgery,After 60 min of reperfusion,the intestine was examined for mor-phological alterations,and after 24 h intestinal basic electrical rhythm(BER)frequency was calculated,and intestinal transit determined in all groups.RESULTS:The intestinal mucosa in rats that were anesthetized with ketamine showed moderate alterations such as epithelial lifting,while ulceration and hemorrhage was observed in rats that received pento-barbital sodium after 60 min of reperfusion.Quantitative analysis of structural damage using the Chiu scale showed significantly Iess injury in rats that received ketamine than in rats that did not(2.35±1.14 vs 4.58 ±0.50,P<0.0001).The distance traveled by a marker,expressed as percentage of total intestinal length,in rats that received pentobarbital sodium was 20% ± 2% in comparison with 25.9% ±1.64% in rats that received ketamine(P=0.017).BER was not statistically different between groups.CONCLUSION:Our results show that ketamine anesthesia is associated with diminished intestinal iniury and abolishes the intestinal transit delay induced by ischemia/reperfusion.(C)2008 The WJG Press.All rights reserved.

  5. Melatonin protects liver from intestine ischemia reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Jian-Yi Li; Hong-Zhuan Yin; Xi Gu; Yong Zhou; Wen-Hai Zhang; Yi-Min Qin

    2008-01-01

    AIM:To investigate the protective effect of melatonin on liver after intestinal ischemia-reperfusion injury in rats.METHODS:One hundred and fifty male Wistar rats,weighing 190-210 g,aged 7 wk,were randomly divided into melatonin exposure group,alcohol solvent control group and normal saline control group.Rats in the melatonin exposure group received intraperitoneal (IP) melatonin (20 mg/kg) 30 min before intestinal ischemia-reperfusion (IR),rats in the alcohol solvent control group received the same concentration and volume of alcohol,and rats in the normal saline control group received the same volume of normal saline.Serum samples were collected from each group 0.5,1,6,12,and 24 h after intestinal IR.Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured with an auto-biochemical analyzer.Serum TNF-a was tested by enzyme-linked immunosorbent assay (ELISA).Malondialdehyde (MDA) in liver was detected by colorimetric assay.Pathological changes in liver and immunohistochemical straining of ICAM-1 were observed under an optical microscope.RESULTS:The levels of ALT measured at various time points after intestinal IR in the melatonin exposure group were significantly lower than those in the other two control groups (P<0.05).The serum AST levels 12 and 24 h after intestinal IR and the ICAM-1 levels (%) 6,12 and 24 h after intestinal IR in the melatonin exposure group were also significantly lower than those in the other two control groups (P<0.05).CONCLUSION:Exotic melatonin can inhibit the activity of ALT,AST and TNF-a decrease the accumulation of MDA,and depress the expression of ICAM-1 in liver after intestinal IR injury,thus improving the liver function.

  6. Reactive changes in astrocytes, and delayed neuronal death, in the rat hippocampal CA1 region following cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Guiqing Zhang; Xiang Luo; Zhiyuan Yu; Chao Ma; Shabei Xu; Wei Wang

    2009-01-01

    BACKGROUND: Blood supply to the hippocampus is not provided by the middle cerebral artery. However, previous studies have shown that delayed neuronal death in the hippocampus may occur following focal cerebral ischemia induced by middle cerebral artery occlusion. OBJECTIVE: To observe the relationship between reactive changes in hippocampal astrocytes and delayed neuronal death in the hippocampal CA1 region following middle cerebral artery occlusion. DESIGN, TIME AND SETTING: The immunohistochemical, randomized, controlled animal study was performed at the Laboratory of Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, from July to November 2007. MATERIALS: Rabbit anti-glial fibrillary acidic protein (GFAP) (Neomarkers, USA), goat anti-rabbit IgG (Sigma, USA) and ApoAlert apoptosis detection kit (Biosciences Clontech, USA) were used in this study. METHODS: A total of 42 healthy adult male Wistar rats, aged 3-5 months, were randomly divided into a sham operation group (n = 6) and a cerebral ischemia/reperfusion group (n = 36). In the cerebral ischemia/reperfusion group, cerebral ischemia/reperfusion models were created by middle cerebral artery occlusion. In the sham operation group, the thread was only inserted into the initial region of the internal carotid artery, and middle cerebral artery occlusion was not induced. Rats in the cerebral ischemia/reperfusion group were assigned to a delayed neuronal death (+) subgroup and a delayed neuronal death (-) subgroup, according to the occurrence of delayed neuronal death in the ischemic side of the hippocampal CA1 region following cerebral ischemia. MAIN OUTCOME MEASURES: Delayed neuronal death in the hippocampal CA1 region was measured by Nissl staining. GFAP expression and delayed neuronal death changes were measured in the rat hippocampal CA1 region at the ischemic hemisphere by double staining for GFAP and TUNEL. RESULTS: After 3 days of ischemia/reperfusion

  7. Melatonin Protects N2a against Ischemia/Reperfusion Injury through Autophagy Enhancement

    Institute of Scientific and Technical Information of China (English)

    国艳春; 王剑飞; 王忠强; 杨易; 王西明; 段秋红

    2010-01-01

    Researches have shown that melatonin is neuroprotectant in ischemia/reperfusion-mediated injury.Although melatonin is known as an effective antioxidant,the mechanism of the protection cannot be explained merely by antioxidation.This study was devoted to explore other existing mechanisms by investigating whether melatonin protects ischemia/reperfusion-injured neurons through elevating autophagy,since autophagy has been frequently suggested to play a crucial role in neuron survival.To find it out,an ischemia/...

  8. Hematological and hemostaseological alterations after warm and cold limb ischemia-reperfusion in a canine model Alterações hematológicas e hemostaseológicas após isquemia-reperfusão morna e fria de membro inferior em modelo canino

    Directory of Open Access Journals (Sweden)

    Miklos Szokoly

    2009-10-01

    Full Text Available PURPOSE: Acute ischemia-reperfusion (I/R of extremities means serious challenge in the clinical practice. Furthermore, the issue of preventive cooling is still controversial. In this canine model we investigated whether limb I/R -with or without cooling- has an influence on hematological and hemostaseological factors. METHODS: Femoral vessels were exposed and clamped for 3 hours. After release the clamps, 4-hour reperfusion was secured. The same procedures with cooling using ice bags, as well as warm and cold sham-operations were performed. Before operations, from the excluded limb by the end of ischemia, during the reperfusion, and for 5 postoperative days afterwards blood samples were collected for testing hematological and blood coagulation parameters. RESULTS: After I/R activated partial thromboplastin time was elongated on 2nd-4th postoperative days. The highest values were on the 2nd day in cold I/R group, accompanied by increased prothrombin time values. The hematological parameters and fibrinogen level showed non-specific changes. In excluded ischemic limb the blood composition showed controversial data. Cold ischemia induced larger alterations, however platelet count, hematocrit changed more expressly in warm ischemia. CONCLUSION: These results indicate the risk of coagulopathy following limb I/R on early post-eventually days, which risk is higher in the case of cold I/R.OBJETIVO: Isquemia-Reperfusão aguda (I/R de extremidades representa um desafio sério na prática clínica. Além disso, o tema de prevenção pelo resfriamento é ainda controverso. Nesse modelo canino, investigou-se se I/R de membros -com ou sem resfriamento- tem influência nos fatores hematológicos e hemostaseológicos. MÉTODOS: Os vasos femorais foram expostos e clampeados por 3 horas. Após liberação dos clampes, foi realizada a reperfusão por 4-horas. Os mesmos procedimentos com e sem resfriamento usando bolsas de gelo, assim como operações simuladas com

  9. Protective Effects and Mechanism of Puerarin on Learning-Memory Disorder after Global Cerebral Ischemia-Reperfusion Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    WU Hai-qin; GUO He-na; WANG Hu-qing; CHANG Ming-ze; ZHANG Gui-lian; ZHAO Ying-xian

    2009-01-01

    Objective: To observe the effect of puerarin on the learning-memory disorder after global cerebral ischemia-reperfusion injury in rats, and to explore its mechanism of action. Methods: The global cerebral ischemia-reperfusion injury model was established using the modified Pulsinelli four-vessel occlusion in Sprague-Dawley rats. Rats were intraperitoneally injected with puerarin (100 mg/kg) 1 h before ischemia and once every 6 h afterwards. The learning-memory ability was evaluated by the passive avoidance test. The dynamic changes of the cell counts of apoptosis and positive expression of Bcl-2 in the hippocampus CA1 region were determined by the TUNEL and immunohistochemical methods, respectively. Results: (1) Compared with the reperfusion group, the step through latency (STL) in the passive avoidance test in the puerarin group was prolonged significantly (P<0.01). (2) The apoptotic neurons were injured most severely on the 3rd day in the hippocampal CA1 region after global ischemia and reperfusion. In the pueradn group, the number of apoptotic cells decreased at respective time points after ischemia-reperfusion (P<0.01). (3) The level of positive expression of Bcl-2 varied according to the duration of reperfusion and the peak level occurred on day 1 in the hippocampal CA1 region after global cerebral ischemia. Compared with the reperfusion group, the expression of Bcl-2 in the pueradn group was up-regulated at the respective time points after ischemia raperfusion (P<0.01), reaching the peak on day 1. Conclusions: Puerarin could improve the learning-memory ability after global cerebral ischemia and reperfusion in rats. The protective mechanism might be related to the effect of inhibiting or delaying the cell apoptosis through up-regulating the expression of Bcl-2 after ischemia and reperfusion.

  10. Protective effect of dietary n-3 polyunsaturated fatty acids on myocardial resistance to ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Zeghichi-Hamri, Sabrina; de Lorgeril, Michel; Salen, Patricia; Chibane, Mohamed; de Leiris, Joël; Boucher, François; Laporte, François

    2010-12-01

    Dietary n-3 polyunsaturated fatty acids (PUFA) reduce coronary heart disease (CHD) complications, such as chronic arrhythmia and sudden cardiac death. Improved myocardial resistance to ischemia-reperfusion injury results in smaller myocardial infarction, which is a major factor in the occurrence of CHD complications. We hypothesized that a specific dietary fatty acid profile (low in saturated and n-6 PUFA but high in plant and marine n-3 PUFA) may improve myocardial resistance to ischemia-reperfusion injury and reduce infarct size. To test this assumption, we used a well-defined rat model of myocardial infarction. Based on our results, in comparison to a diet that is high in either saturated or n-6 PUFA but poor in plant and marine n-3 PUFA, a diet that is low in saturated fats and n-6 PUFA but rich in plant and marine n-3 PUFA results in smaller myocardial infarct size (P fatty acid composition of plasma, erythrocyte cell membranes, and the phospholipids of myocardial mitochondria. The results show a great accumulation of n-3 PUFA and a parallel decrease in arachidonic acid, the main n-6 PUFA, in plasma, cell membranes, and cardiac mitochondria (P < .0001). We conclude that improved myocardial resistance to ischemia-reperfusion may be one of the critical factors explaining the protective effects of dietary n-3 PUFA against CHD complications in humans. In addition to increasing n-3 PUFA intake, an optimal dietary pattern aimed at reducing cardiovascular mortality should include a reduction of the intake of both saturated and n-6 PUFA.

  11. Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway

    Institute of Scientific and Technical Information of China (English)

    Xiaojie Liu; Zhigang Mei; Jingping Qian; Yongbao Zeng; Mingzhi Wang

    2013-01-01

    Puerarin, a major isoflavonoid derived from the Chinese medical herb radix puerariae (Gegen), has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebral ischemia model rats. Recent findings regarding stroke pathophysiology have recognized that an-ti-inflammation is an important target for the treatment of ischemic stroke. The cholinergic an-ti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control. This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be in-volved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment (intravenous injection) re-duced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-αin brain tissue. Pretreatment with puerarin (intravenous injection) attenuated the inflammatory response in rats, which was accompanied by janus-activated kinase 2 (JAK2) and signal transducers and activators of transcription 3 (STAT3) activation and nuclear factor kappa B (NF-κB) inhibition. These observa-tions were inhibited by the alpha7 nicotinic acetylcholine receptor (α7nAchR) antagonistα-bungarotoxin (α-BGT). In addition, puerarin pretreatment increased the expression of α7nAchR mRNA in ischemic cerebral tissue. These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory re-sponse. Our results also indicated that the anti-inflammatory effect of puerarin may partly be me-diated through the activation of the cholinergic anti-inflammatory pathway.

  12. A novel targeted inhibitor of the alternative pathway of complement and its therapeutic application in ischemia/reperfusion injury.

    Science.gov (United States)

    Huang, Yuxiang; Qiao, Fei; Atkinson, Carl; Holers, V Michael; Tomlinson, Stephen

    2008-12-01

    Bioavailability and therapeutic efficacy of soluble Crry, a mouse inhibitor of all complement activation pathways, is significantly enhanced when linked to a fragment of complement receptor 2 (CR2), a receptor that targets C3 activation products. In this study, we characterize alternative pathway-specific inhibitors consisting of a single or dimeric N-terminal region of mouse factor H (fH; short consensus repeats 1-5) linked to the same CR2 fragment (CR2-fH and CR2-fHfH). Both CR2-fH and CR2-fHfH were highly effective at inhibiting the alternative pathway in vitro and demonstrated a higher specific activity than CR2-Crry. CR2-fH was also more effective than endogenous serum fH in blocking target deposition of C3. Target binding and complement inhibitory activity of CR2-fH/CR2-fHfH was dependent on CR2- and C3-mediated interactions. The alternative pathway of complement plays a role in intestine ischemia/reperfusion injury. However, serum fH fails to provide protection against intestine ischemia/reperfusion injury although it can bind to and provide cell surfaces with protection from complement and is present in plasma at a high concentration. In a mouse model, CR2-fH and CR2-fHfH provided complete protection from local (intestine) and remote (lung) injury. CR2-fH targeted to the site of local injury and greatly reduced levels of tissue C3 deposition. Thus, the targeting mechanism significantly enhances alternative pathway-specific complement inhibitory activity of the N-terminal domain of fH and has the potential to reduce side effects that may be associated with systemic complement blockade. The data further indicate alternative pathway dependence for local and remote injury following intestinal ischemia/reperfusion in a clinically relevant therapeutic paradigm.

  13. Melatonin treatment protects liver of Zucker rats after ischemia/reperfusion by diminishing oxidative stress and apoptosis.

    Science.gov (United States)

    Kireev, Roman; Bitoun, Samuel; Cuesta, Sara; Tejerina, Alejandro; Ibarrola, Carolina; Moreno, Enrique; Vara, Elena; Tresguerres, Jesus A F

    2013-02-15

    Fatty livers occur in up to 20% of potential liver donors and increase cellular injury during the ischemia/reperfusion phase, so any intervention that could enable a better outcome of grafts for liver transplantation would be very useful. The effect of melatonin on liver ischemia/reperfusion injury in a rat model of obesity and hepatic steatosis has been investigated. Forty fa/fa Zucker rats were divided in 4 groups. 3 groups were subjected to 35 min of warm hepatic ischemia and 36 h of reperfusion. One experimental group remained untreated and 2 were given 10mg/kg melatonin intraperitoneally or orally. Another group was sham-operated. Plasma ALT, AST and hepatic content of ATP, MDA, hydroxyalkenals, NOx metabolites, antioxidant enzyme activity, caspase-9 and DNA fragmentation were determined in the liver. The expression of iNOS, eNOS, Bcl2, Bax, Bad and AIF were determined by RT-PCR Melatonin was effective at decreasing liver injury by both ways as assessed by liver transaminases, markers of apoptosis, of oxidative stress and improved liver ATP content. Melatonin administration decreased the activities or levels of most of the parameters measured in a beneficial way, and our study identified also some of the mechanisms of protection. We conclude that administration of melatonin improved liver function, as well as markers of pro/antioxidant status and apoptosis following ischemia/reperfusion in obese rats with fatty liver. These data suggest that this substance could improve outcome in patients undergoing liver transplantation who receive a fatty liver implant and suggest the need of clinical trials with it in liver transplantation.

  14. Triptolide inhibits NF-κB activation and reduces injury of donor lung induced by ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Jing-kang HE; Shu-dong YU; Hong-Jun ZHU; Jun-chao WU; Zhen-ghong QIN

    2007-01-01

    Aim: To investigate the protective effect of triptolide (TRI) on ischemia/reperfusion- induced injury of transplanted rabbit lungs and to investigate the mechanisms underlying the actions of TRI. Methods: We established the rabbit lung trans- plantation model and studied lung injury induced by ischemia/reperfusion and the inhibitory effect of TRI on NF-r,B. The severity of lung injury was determined by a gradual decline in PvO2, the degree of lung edema, the increase in the myeloperoxidase (MPO) activity, and the ultrastructural changes of transplanted lungs. The activation of NF-r,B was measured by immunohistochemistry. The increase in intercellular adhesion molecule- 1 (ICAM- 1), which is the target gene of NF-κB, was evaluated by ELISA. Results: After reperfusion, there was a gradual decline in the PvO2 level in the control group (group I). The level of PvO2 in the group treated with lipopolysaccharide (group Ⅱ) was significantly decreased, whereas that of the group treated with TRI (group Ⅲ) was markedly improved (P<0.01). In group Ⅲ, the activity of MPO was downregulated, and the pulmonary edema did not become severe and the ultrastructure of the donor lung remained normal. The activity of NF-κB and the expression of ICAM-1 was significantly increased in the donor lungs. TRI blocked NF-κB activation and ICAM-1 expression. Conclusion: The effects of TRI on reducing injury to donor lungs induced by ischemia/reperfusion may possibly be mediated by inhibiting the activity of NF-κB and the expression of the NF-rd3 target gene ICAM-1. Thus, TRI could be used in lung transplantations for improving the function of donor lungs.

  15. Novel curcumin analogue 14p protects against myocardial ischemia reperfusion injury through Nrf2-activating anti-oxidative activity

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weixin [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wu, Mingchai [Department of Pharmacy, The Third Affiliated Hospital of Wenzhou Medical University, Wenzou, Zhejiang (China); Tang, Longguang; Pan, Yong; Liu, Zhiguo [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zeng, Chunlai [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Wang, Jingying [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wei, Tiemin, E-mail: lswtm@sina.com [Department of Cardiology, The 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang (China); Liang, Guang, E-mail: wzmcliangguang@163.com [Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2015-01-15

    Background: Alleviating the oxidant stress associated with myocardial ischemia reperfusion has been demonstrated as a potential therapeutic approach to limit ischemia reperfusion (I/R)-induced cardiac damage. Curcumin, a natural compound with anti-oxidative activity, exerts beneficial effect against cardiac I/R injury, but poor chemical and metabolic stability. Previously, we have designed and synthesized a series of mono-carbonyl analogues of curcumin (MACs) with high stability. This study aims to find new anti-oxidant MACs and to demonstrate their effects and mechanisms against I/R-induced heart injury. Methods: H9c2 cells challenged with H{sub 2}O{sub 2} or TBHP were used for in vitro bio-screening and mechanistic studies. The MDA, H{sub 2}O{sub 2} and SOD levels in H9C2 cells were determined, and the cell viability was assessed by MTT assay. Myocardial I/R mouse models administrated with or without the compound were used for in vivo studies. Results: The in vitro cell-based screening showed that curcumin analogues 8d and 14p exhibited strong anti-oxidative effects. Pre-treatment of H9c2 cells with 14p activated Nrf2 signaling pathway, attenuated H{sub 2}O{sub 2}-increased MDA and SOD level, followed by the inhibition of TBHP-induced cell death and Bax/Bcl-2–caspase-3 pathway activation. Silencing Nrf2 significantly reversed the protective effects of 14p. In in vivo animal model of myocardial I/R, administration of low dose 14p (10 mg/kg) reduced infarct size and myocardial apoptosis to the same extent as the high dose curcumin (100 mg/kg). Conclusion: These data support the novel curcumin analogue 14p as a promising antioxidant to decrease oxidative stress and limit myocardial ischemia reperfusion injury via activating Nrf2. - Highlights: • Mono-carbonyl analogue of curcumin, 14p, exhibited better chemical stability. • Compound 14p inhibited TBHP-induced apoptosis through activating Nrf2 in vitro. • Compound 14p limited myocardial ischemia/reperfusion

  16. Crucial role of SLP-76 and ADAP for neutrophil recruitment in mouse kidney ischemia-reperfusion injury.

    Science.gov (United States)

    Block, Helena; Herter, Jan M; Rossaint, Jan; Stadtmann, Anika; Kliche, Stefanie; Lowell, Clifford A; Zarbock, Alexander

    2012-02-13

    Neutrophils trigger inflammation-induced acute kidney injury (AKI), a frequent and potentially lethal occurrence in humans. Molecular mechanisms underlying neutrophil recruitment to sites of inflammation have proved elusive. In this study, we demonstrate that SLP-76 (SH2 domain-containing leukocyte phosphoprotein of 76 kD) and ADAP (adhesion and degranulation promoting adaptor protein) are involved in E-selectin-mediated integrin activation and slow leukocyte rolling, which promotes ischemia-reperfusion-induced AKI in mice. By using genetically engineered mice and transduced Slp76(-/-) primary leukocytes, we demonstrate that ADAP as well as two N-terminal-located tyrosines and the SH2 domain of SLP-76 are required for downstream signaling and slow leukocyte rolling. The Tec family kinase Bruton tyrosine kinase is downstream of SLP-76 and, together with ADAP, regulates PI3Kγ (phosphoinositide 3-kinase-γ)- and PLCγ2 (phospholipase Cγ2)-dependent pathways. Blocking both pathways completely abolishes integrin affinity and avidity regulation. Thus, SLP-76 and ADAP are involved in E-selectin-mediated integrin activation and neutrophil recruitment to inflamed kidneys, which may underlie the development of life-threatening ischemia-reperfusion-induced AKI in humans.

  17. Effects of nerve growth factor on the expression of caspase-12 of nerve cells in cerebral ischemia/reperfusion area

    Institute of Scientific and Technical Information of China (English)

    Jiping Yang; Huaijun Liu; Ying Li; Yan Liu; Haiqing Yang

    2006-01-01

    BACKGROUND: Researches suggest that cascade reaction of cysteine protease mediated by caspase-12 can cause apoptosis after cerebral ischemia/reperfusion injury;however, nerve growth factor (NGF) can reduce apoptosis through inhibiting activation of that reaction.OBJECTTVE: To observe the effect of NGF on the expression of caspase-12 in brain tissue of rabbits with cerebral ischemia/reperfusion injury, and elucidate the protective mechanism of NGF on neural apoptosis induced by cerebral ischemia/reperfusion injury.DESIGN: Randomized controlled animal study.SETTING: Department of Image, Second Hospital, Hebei Medical University.MATERIALS: A total of 26 healthy New Zealand rabbits, of clean grade, aged 4.5-5 months, weighing (2.6±0.2) kg, were selected in this study. Reagents: NGF (Xiamen Beida Zhilu Biotechnology Co., Ltd.);caspase-12 (Santa Cruz Biotechnology Company, USA, clone number: SC-12395); caspase-3 (Santa Cruz Biotechnology Company, USA, clone number: SC-7272); biotin-antibody Ⅱ and ABC compound (Wuhan Boster Company); in situ end-labeling (ISEL, Beijing Zhongshan Company).METHODS: The experiment was carried out in the Laboratories of Nerve Molecule Image Science and Neurology of the Second Hospital of Hebei Medical University from May to August 2005. ① All animals were randomly divided into three groups. Ischemia/reperfusion (I/R) group (n=10): Left middle cerebral artery (MCA) was blocked for 2 hours and then blooded for 2 hours in order to establish focal cerebral ischemia/reperfusion models. Sham operation group (n=6): Cork was inserted with 3 cm in depth, and then pulled to common carotid artery. Other procedures were as the same as those in ischemia/reperfusion group.Treatment group (n=10): After modeling, 400 AU (16 μg/L) NGF was inserted into cerebral infarction focus sham operation group and at 3 days after reperfusion in other two groups. In addition, contents of caspase-12 and caspase-3 were measured with immunohistochemical technique; mean

  18. Radix Ilicis Pubescentis total flavonoids combined with mobilization of bone marrow stem cells to protect against cerebral ischemia/reperfusion injury

    OpenAIRE

    Ming-san Miao; Lin Guo; Rui-qi Li; Xiao Ma

    2016-01-01

    Previous studies have shown that Radix Ilicis Pubescentis total flavonoids have a neuroprotective effect, but it remains unclear whether Radix Ilicis Pubescentis total flavonoids have a synergistic effect with the recombinant human granulocyte colony stimulating factor-mobilized bone marrow stem cell transplantation on cerebral ischemia/reperfusion injury. Rat ischemia models were administered 0.3, 0.15 and 0.075 g/kg Radix Ilicis Pubescentis total flavonoids from 3 days before modeling to 2 ...

  19. Transplantation of human amnion-derived mesenchymal stem cells alleviates ischemia-reperfusion-induced acute lung injury after cardiopulmonary bypass%人羊膜间充质干细胞移植减轻体外循环再灌注肺损伤

    Institute of Scientific and Technical Information of China (English)

    强勇; 梁贵友; 余丽梅; 齐斌; 高振宇

    2016-01-01

    BACKGROUND:In recent years, mesenchymal stem cels exhibit a good prospect in organ or tissue repair and therefore, and therefore, cel transplantation based on mesenchymal stem cel plasticity can promote cel regeneration and functional recovery from lung injury after cardiopulmonary bypass. OBJECTIVE:To investigate the effects of human amnion-derived mesenchymal stem cels (hAMSCs) transplantation on ischemia-reperfusion-induced acute lung injury in dogs after cardiopulmonary bypassand its mechanism for regulating inflammatory cytokines. METHODS:Eighteen adult healthy mongrel dogs were randomly divided into three groups (n=6 per group): black group (cardiopulmonary bypass with 1 mL physiological saline injectionvia the femoral vein without blocking the aorta), control group (cardiopulmonary bypass with blocking the aorta for 1 hour and then opening the aorta for 15 minutes plus 1 mL physiological saline injectionvia the femoral vein), experiment group (cardiopulmonary bypass with blocking the aorta for 1 hour and then opening the aorta for 15 minutes plus femoral vein injection of 1 mL physiological saline containing 2×107 hAMSCs). Arterial blood samples of 2 mL were taken to calculate oxygenation index and respiratory index before cardiopulmonary bypass (T1), 15 minutes (T2), 1 hour (T3), 2 hours (T4), 3 hours (T5) after opening the aorta. 8 mL intravenous blood samples were taken to detect the serum tumor necrosis factor α, matrix metaloproteinase-9, interleukin-8 and interleukin-10 by ELISA. Meanwhile, western blot assay was used to detect the expression of nuclear factor-κB in lung tissues, and histopathological changes of lung tissues observed under optical microscope. RESULTS AND CONCLUSION:Compared with the control group, the oxygenation index was significantly increased in the experimental group at 2 and 3 hours after transplantation, and the respiratory index was remarkably decreased at 1, 2, 3 hours after transplantation. Compared with the control group

  20. Neuroprotective effect ofShenqi Fuzheng injection pretreatment in aged rats with cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Ying-min Cai; Yong Zhang; Peng-bo Zhang; Lu-ming Zhen; Xiao-ju Sun; Zhi-ling Wang; Ren-yan Xu; Rong-liang Xue

    2016-01-01

    Shenqi Fuzheng injection is extracted from the Chinese herbsRadix Astragali andRadix Codonopsis. The aim of the present study was to investigate the neuroprotective effects of Shenqi Fuzheng injection in cerebral ischemia and reperfusion. Aged rats (20–22 months) were divided into three groups: sham, model, and treatment.Shenqi Fuzheng injection or saline (40 mL/kg) was injected into the tail vein daily for 1 week, after which a cerebral ischemia/reperfusion injury model was established. Compared with model rats that received saline, rats in the treatment group had smaller infarct volumes, lower brain water and malondialdehyde content, lower brain Ca2+levels, lower ac-tivities of serum lactate dehydrogenase and creatine kinase, and higher superoxide dismutase activity. In addition, the treatment group showed less damage to the brain tissue ultrastructure and better neurological function. Our ifndings indicate thatShenqi Fuzheng injec-tion exerts neuroprotective effects in aged rats with cerebral ischemia/reperfusion injury, and that the underlying mechanism relies on oxygen free radical scavenging and inhibition of brain Ca2+ accumulation.

  1. Protection Against Hepatic Ischemia-reperfusion Injury in Rats by Oral Pretreatment With Quercetin

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective To investigate the possible protection provided by oral quercetin pretreatment against hepatic ischemia-reperfusion injury in rats. Methods The quercetin (0.13 mmol/kg) was orally administrated in 50 min prior to hepatic ischemia-reperfusion injury. Ascorbic acid was also similarly administered. The hepatic content of quercetin was assayed by high performance liquid chromatography (HPLC). Plasma glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) activities and malondialdehyde (MDA) concentration were measured as markers of hepatic ischemia-reperfusion injury. Meanwhile, hepatic content of glutathione (GSH), activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO), total antioxidant capacity (TAOC), contents of reactive oxygen species (ROS) and MDA, DNA fragmentation were also determined. Results Hepatic content of quercetin after intragastric administration of quercetin was increased significantly. The increases in plasma GPT, GOT activities and MDA concentration after hepatic ischemia-reperfusion injury were reduced significantly by pretreatment with quercetin. Hepatic content of GSH and activities of SOD, GSH-Px and TAOC were restored remarkably while the ROS and MDA contents were significantly diminished by quercetin pretreatment after ischemia-reperfusion injury. However, quercetin pretreatment did not reduce significantly hepatic XO activity and DNA fragmentation. Ascorbic acid pretreatment had also protective effects against hepatic ischemia-reperfusion injury by restoring hepatic content of GSH, TAOC and diminishing ROS and MDA formation and DNA fragmentation. Conclusion It is indicated that quercetin can protect the liver against ischemia-reperfusion injury after oral pretreatment and the underlying mechanism is associated with improved hepatic antioxidant capacity.

  2. Taurine inhibits ischemia/reperfusion-induced compartment syndrome in rabbits

    Institute of Scientific and Technical Information of China (English)

    Ji-xian WANG; Yan LI; Li-ke ZHANG; Jing ZHAO; Yong-zheng PANG; Chao-shu TANG; Jing ZHANG

    2005-01-01

    Aim: To investigate effects of taurine on ischemia/reperfusion (I/R)-induced compartment syndrome in rabbit hind limbs.Methods: Rabbits underwent femoral artery occ lusion after ligation of branches from terminal aorta to femoral artery.After a 7-h ischemia, reperfusion was established with the use of heparinized by iv infusion 10 min before shunt placement.During reperfusion, anterior compartment pressure (ACP) was monitored continuously in the left lower extremity.Gastrocnemius muscle triphenyltetrazolium chloride (TTC) level, taurine content and myeloperoxidase activity were assayed.Oxidative stress was induced in the in vitro gastrocnemius muscle slices by free radical generating systems (FRGS),and the malondialdehyde content was measured in presence or absence of taurine.Results: After 7 h of ischemia, none of the parameters that we measured were different from those before ischemia, except that TTC reduction decreased by 80%.In the control group, after 2 h of reperfusion, ACP increased 4.5-fold, and gastrocnemius muscle taurine content was reduced by 33%.In taurine-treated animals, at 2 h reperfusion, the mean arterial blood pressure and heart rate were increased, by 6% and 10%.ACP decreased by 39%, muscle edema decreased by 16%, TTC reduction increased by 150%, and lactate dehydrogenase decreased by 36% compared to control group.Plasma and muscle taurine content increased by 70% and 88%, respectively.In the taurine-treated group, at 2 h reperfusion, plasma malondialdehyde and conjugated diene content were decreased by 38% and 23%,respectively, and muscle malondialdehyde and conjugated diene content decreased by 22% and 30%, respectively compared to the control group.At 2 h reperfusion,myeloperoxidase activity was increased 3.5-fold in control animals.In the in vitro study, taurine decreased malondialdehyde content in muscle slices incubated with hypochlorous acid in a dose-dependent manner, but there was no change when incubated with hydrogen peroxide and

  3. Effect of Shenfu Injection (ginesenoside and aconite alkaloid) on the apoptosis of intestinal mucosal epithelial cells and its mechanism during ischemia-reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    夏中元; 孟庆涛; 张帆; 陈向东

    2004-01-01

    Objective: To investigate the effect of Shenfu Injection (SF, ginesenoside and aconite alkaloid) on the apoptosis of intestinal mucosal epithelial cells during ischemia-reperfusion in rats and its potential mechanisms. Methods: Ischemia-reperfusion model was established in rats. Twenty-four rats were divided into 3 groups with 8 rats in each, eg, ischemia-reperfusion (I/R) group, SF-treated group, and control group. In both SF and I/R groups, the superior mesenteric artery was closed with forceps for 1 hour and then reperfused for 2 hours. Either SF (3 ml/kg, SF group) or normal saline (I/R and control groups) was injected intravenously and continuously for 5 ml/kg with a micropump before the superior mesenteric artery was closed. The superior mesenteric artery was not closed for animals in control group. The expression of casapse-3 and Fas, and the level of TNF-α and pathological changes of the ileal mucosal tissue were assayed. Results: (1) The number of apoptosis cells increased obviously in I/R group and was significantly higher than that in SF and control groups (P<0.05). (2) The expression of caspase-3, Fas, and TNF-α was significantly higher in I/R group than SF and control groups (P<0.01); however, there was not significant difference in the expression of capase-3 between control group and SF group. There was a positive correlation between the expression of caspase-3, Fas, and TNF-α, and the number of apoptosis cells. (3) Under light microscope, intestinal mucosal impairment was found milder in SF group than I/R group (P<0.05). Conclusions: SF can depress the apoptosis of intestinal mucosal epithelial cells during ischemia-reperfusion by restraining the expression of TNF-α, Fas, caspase-3, and accordingly alleviate the ischemia and reperfusion injury of intestinal mucosal epithelial cells.

  4. Effect of Electroacupuncture on TRPM7 mRNA Expression after Cerebral Ischemia/reperfusion in Rats via TrkA Pathway

    Institute of Scientific and Technical Information of China (English)

    ZHAO Li; SHI Jing; SUN Ning; TIAN Shunlian; MENG Xianfang; LIU Xiaochun; LI Lingli

    2005-01-01

    Summary: The effect of electroacupuncture (EA) on TRPM7 mRNA expression of focal cerebral ischemia in rats and further the role of EA in the relationship between TRPM7 and trkA pathway was investigated. Thirty SD rats were randomly divided into 5 groups : normal group, ischemia/reperfusion group, EA treated group (ischemic rats with EA treatment), TE infusion group (ischemic rats with EA treatment and TE buffer infusion),AS-ODN group (ischemic rats with EA treatment and antisense trkA oligonucleotide infusion). The stroke animal model was established by the modified method of middle cerebral artery occlusion. Antisense trkA oligonucleotide that blocked NGF's effects was injected into cerebroventricle before EA. The TRPM7 mRNA was detected by RT-PCR method. The results showed that there were low TRPM7 mRNA levels in cortex and hippocampus in normal group. Compared with normal group, TRPM7 mRNA expression was increased significantly in ischemia/reperfusion group (P<0.05). A significant reduction in the expression of TRPM7 mRNA was found in EA treated group in contrast to ischemia/reperfusion group (P<0.05). The expression of TRPM7 mRNA in AS-ODN group was remarkably increased compared with EA treated group and TE infusion group (P<0.05). The results indicated that TRPM7 channels in the ischemic cortex and hippocampus in rats might play a key role in ischemic brain injury. EA could reverse the overexpression of TRPM7 in cerebral ischemia/reperfusion rats. And the inhibitory effect of EA on TRPM7 channels might be through trkA pathway.

  5. Transient focal cerebral ischemia/reperfusion induces early and chronic axonal changes in rats: its importance for the risk of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Qinan Zhang

    Full Text Available The dementia of Alzheimer's type and brain ischemia are known to increase at comparable rates with age. Recent advances suggest that cerebral ischemia may contribute to the pathogenesis of Alzheimer's disease (AD, however, the neuropathological relationship between these two disorders is largely unclear. It has been demonstrated that axonopathy, mainly manifesting as impairment of axonal transport and swelling of the axon and varicosity, is a prominent feature in AD and may play an important role in the neuropathological mechanisms in AD. In this study, we investigated the early and chronic changes of the axons of neurons in the different brain areas (cortex, hippocampus and striatum using in vivo tracing technique and grading analysis method in a rat model of transient focal cerebral ischemia/reperfusion (middle cerebral artery occlusion, MCAO. In addition, the relationship between the changes of axons and the expression of β-amyloid 42 (Aβ42 and hyperphosphorylated Tau, which have been considered as the key neuropathological processes of AD, was analyzed by combining tracing technique with immunohistochemistry or western blotting. Subsequently, we found that transient cerebral ischemia/reperfusion produced obvious swelling of the axons and varicosities, from 6 hours after transient cerebral ischemia/reperfusion even up to 4 weeks. We could not observe Aβ plaques or overexpression of Aβ42 in the ischemic brain areas, however, the site-specific hyperphosphorylated Tau could be detected in the ischemic cortex. These results suggest that transient cerebral ischemia/reperfusion induce early and chronic axonal changes, which may be an important mechanism affecting the clinical outcome and possibly contributing to the development of AD after stroke.

  6. Antioxidant effects of ethyl acetate extract of Desmodium gangeticum root on myocardial ischemia reperfusion injury in rat hearts

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    Raman Archana

    2010-01-01

    Full Text Available Abstract Background This study aims to evaluate the antioxidant potential of the ethyl acetate extract of Desmodium gangeticum root for cardioprotection from ischemia reperfusion-induced oxidative stress. Methods The in vitro antioxidant potential of the extract was in terms of hydroxyl radical scavenging activity, lipid peroxide scavenging activity, nitric oxide scavenging activity and diphenylpicrylhydrazyl radical scavenging activity. The in vivo antioxidant potential of the extract was assessed in an isolated rat heart model. Results Free radicals were scavenged by the extract in a concentration-dependent manner within the range of the given concentrations in all models. Administration of the ethyl acetate extract of Desmodium gangeticum root (100 mg per kg body weight before global ischemia caused a significant improvement of cardiac function and a decrease in the release of lactate dehydrogenase in coronary effluent, as well as the level of malondialdehyde in myocardial tissues. Conclusion The ethyl acetate extract of Desmodium gangeticum root protects the myocardium against ischemia-reperfusion-induced damage in rats. The effects of the extract may be related to the inhibition of lipid peroxidation.

  7. Cardioprotective Effects of Genistin in Rat Myocardial Ischemia-Reperfusion Injury Studies by Regulation of P2X7/NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Meng Gu

    2016-01-01

    Full Text Available The present study aimed to assess the effects and mechanisms of genistin in the rat model of myocardial ischemia reperfusion injury. The rat hearts were exposed to the left anterior descending coronary artery (LAD ligation for 30 min followed by 1 h of reperfusion. In the rat of myocardial ischemia/reperfusion (MI/R, it was found that genistin pretreatment reduced myocardial infarct size, improved the heart rate, and decreased creatine kinase (CK and lactate dehydrogenase (LDH levels in coronary flow. This pretreatment also increased catalase (CAT, superoxide dismutase (SOD activities but decreased glutathione (GSH, malondialdehyde (MDA levels. Furthermore, we determined that genistin can ameliorate the impaired mitochondrial morphology and oxidation system; interleukin-6 (IL-6, interleukin-8 (IL-8, interleukin-10 (IL-10, and tumor necrosis factor-α (TNF-α levels were also recovered. Besides, related-proteins of nuclear factor kappa-B (NF-κB signal pathway activated by P2X7 were investigated to determine the molecular mechanism of genistin and their expressions were measured by western blot. These results presented here demonstrated that genistin enhanced the protective effect on the rats with myocardial ischemia reperfusion injury. Therefore, the cardioprotective effects of genistin may rely on its antioxidant and anti-inflammatory activities via suppression of P2X7/NF-κB pathways.

  8. Momordica charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway.

    Science.gov (United States)

    Gong, Juanjuan; Sun, Fumou; Li, Yihang; Zhou, Xiaoling; Duan, Zhenzhen; Duan, Fugang; Zhao, Lei; Chen, Hansen; Qi, Suhua; Shen, Jiangang

    2015-04-01

    Momordica charantia (MC) is a medicinal plant for stroke treatment in Traditional Chinese Medicine, but its active compounds and molecular targets are unknown yet. M. charantia polysaccharide (MCP) is one of the important bioactive components in MC. In the present study, we tested the hypothesis that MCP has neuroprotective effects against cerebral ischemia/reperfusion injury through scavenging superoxide (O2(-)), nitric oxide (NO) and peroxynitrite (ONOO(-)) and inhibiting c-Jun N-terminal protein kinase (JNK3) signaling cascades. We conducted experiments with in vivo global and focal cerebral ischemia/reperfusion rat models and in vitro oxygen glucose deprivation (OGD) neural cells. The effects of MCP on apoptotic cell death and infarction volume, the bioactivities of scavenging O2(-), NO and ONOO(-), inhibiting lipid peroxidation and modulating JNK3 signaling pathway were investigated. Major results are summarized as below: (1) MCP dose-dependently attenuated apoptotic cell death in neural cells under OGD condition in vitro and reduced infarction volume in ischemic brains in vivo; (2) MCP had directing scavenging effects on NO, O2(-) and ONOO(-) and inhibited lipid peroxidation; (3) MCP inhibited the activations of JNK3/c-Jun/Fas-L and JNK3/cytochrome C/caspases-3 signaling cascades in ischemic brains in vivo. Taken together, we conclude that MCP could be a promising neuroprotective ingredient of M. charantia and its mechanisms could be at least in part attributed to its antioxidant activities and inhibiting JNK3 signaling cascades during cerebral ischemia/reperfusion injury.

  9. Neohesperidin attenuates cerebral ischemia-reperfusion injury via inhibiting the apoptotic pathway and activating the Akt/Nrf2/HO-1 pathway.

    Science.gov (United States)

    Wang, Ji-Jun; Cui, Ping

    2013-09-01

    Oxidative stress is well known to play a pivotal role in cerebral ischemia-reperfusion injury. On the basis of this fact, antioxidative agents have been demonstrated to be neuroprotective. Neohesperidin (NH) is abundant in citrus flavonoids and possesses reactive oxygen species scavenging activity and neuroprotective effects in vitro. However, little is known about its effects on cerebral ischemia-reperfusion injury and the underlying mechanisms. In this study, we use a rat model of middle cerebral artery occlusion (MCAO) to investigate the neuroprotective effects of NH. NH significantly improved neurological functions and attenuated MCAO-induced infarct volume, pathological changes, and neuronal loss. Moreover, it enhanced antioxidant capacity and suppressed oxidative stress in the brain. NH inhibited the MCAO-induced upregulation of Bax, cytochrome c, and cleaved caspase-9 and -3, as well as the downregulation of Bcl-2. Interestingly, NH treatment upregulated heme oxygenase-1 (HO-1) in a concentration-dependent manner, which was due to the NH-mediated activation of the protein kinase B (Akt)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. NH also abolished the MCAO-induced inhibition of the Akt/Nrf2 pathway. In conclusion, NH attenuates cerebral ischemia-reperfusion injury via the inhibition of neuronal apoptosis and oxidative stress through the regulation of the apoptotic pathway and the Akt/Nrf2/HO-1 pathway. NH might be a promising preventive agent for ischemic stroke.

  10. Additional Effects of Back-Shu Electroacupuncture and Moxibustion in Cardioprotection of Rat Ischemia-Reperfusion Injury

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    Seung Min Kathy Lee

    2015-01-01

    Full Text Available Many preclinical studies show that electroacupuncture (EA on PC6 and ST36 can reduce infarct size after ischemia-reperfusion (IR injury. Yet studies to enhance the treatment effect size are limited. The purpose of this study was to explore whether EA has additional myocardial protective effects on an ischemia-reperfusion (IR injury rat model when back-shu EA and moxibustion are added. SD rats were divided into several groups and treated with either EA only, EA + back-shu EA (B, or EA + B + moxibustion (M for 5 consecutive days. Transthoracic echocardiography and molecular and immunohistochemical evaluations were performed. It was found that although myocardial infarct areas were significantly lower and cardiac function was also significantly preserved in the three treatment groups compared to the placebo group, there were no additional differences between the three treatment groups. In addition, HSP20 and HSP27 were expressed significantly more in the treatment groups. The results suggest that adding several treatments does not necessarily increase protection. Our study corroborates previous findings that more treatment, such as prolonging EA duration or increasing EA intensity, does not always lead to better results. Other methods of increasing treatment effect size should be explored.

  11. Effects of N-n-butyl Haloperidol Iodide on Myocardial Ischemia/Reperfusion Injury and Egr-1 Expression in Rat

    Institute of Scientific and Technical Information of China (English)

    Yan-Mei ZHANG; Gang-Gang SHI; Zhao TANG; Jin-Hong ZHENG; Wei-Qiu LI; Fu-Xiao GUO; Qiang-Yong JIA

    2006-01-01

    We have previously shown that N-n-butyl haloperidol iodide (F2) derived from haloperidol reduces ischemia/reperfusion-induced myocardial injury by blocking intracellular Ca2+ overload. This study tested the hypothesis that cardio-protection with F2 is associated with an attenuation in the expression of early growth response gene 1 (Egr-1). In an in vivo rat model of 60 min coronary occlusion followed by 180 min of reperfusion, treatment with F2 significantly reduced myocardial injury evidenced by the reduction in release of plasma creatine kinase, myocardial creatine kinase isoenzyme and lactate dehydrogenase. In cultured neonatal rat cardiomyocytes of hypoxia for 3 h and reoxygenation for 1 h, F2 treatment attenuated necrotic and apoptotic cell death, as demonstrated by electron microscopy. Concomitant with cardio-protection by F2, the increased expression levels of Egr-1 mRNA and proteinwere significantly reduced in myocardial tissue and cultured cardiomyocytes as detected by reverse transcription-polymerase chain reaction, immunohistochemistry and immunocytochemistry. In conclusion, these results suggest that the protective effect of F2 on ischemia/reperfusion- or hypoxia/reoxygenation-induced myocardial injury might be partly mediated by downregulating Egr-1 expression.

  12. Evaluation of Liver Ischemia-Reperfusion Injury in Rabbits Using a Nanoscale Ultrasound Contrast Agent Targeting ICAM-1.

    Directory of Open Access Journals (Sweden)

    Fang Xie

    Full Text Available To assess the feasibility of ultrasound molecular imaging in the early diagnosis of liver ischemia-reperfusion injury (IRI using a nanoscale contrast agent targeting anti-intracellular adhesion molecule-1 (anti-ICAM-1.The targeted nanobubbles containing anti-ICAM-1 antibody were prepared using the avidin-biotin binding method. Human hepatic sinusoidal endothelial cells (HHSECs were cultured at the circumstances of hypoxia/reoxygenation (H/R and low temperature. The rabbit liver IRI model (I/R group was established using the Pringle's maneuver. The time-intensity curve of the liver contrast ultrasonographic images was plotted and the peak intensity, time to peak, and time of duration were calculated.The size of the targeted nanobubbles were 148.15 ± 39.75 nm and the concentration was 3.6-7.4 × 109/ml, and bound well with the H/R HHSECs. Animal contrast enhanced ultrasound images showed that the peak intensity and time of duration of the targeted nanobubbles were significantly higher than that of common nanobubbles in the I/R group, and the peak intensity and time of duration of the targeted nanobubbles in the I/R group were also significantly higher than that in the SO group.The targeted nanobubbles have small particle size, stable characteristic, and good targeting ability, which can assess hepatic ischemia-reperfusion injury specifically, noninvasively, and quantitatively at the molecular level.

  13. Protective effects of Ping-Lv-Mixture (PLM), a medicinal formula on arrhythmias induced by myocardial ischemia-reperfusion.

    Science.gov (United States)

    An, Wei; Yang, Jing

    2006-11-03

    Ping-Lv-Mixture (PLM) is a Chinese medicinal formula. The present study aimed to determine the effects of PLM on myocardial ischemia-reperfusion (MI/R) induced arrhythmias in rats. Arrhythmia model was established by occlusion of the left arterial descending coronary artery and thereafter reperfusion. A lead II electrocardiogram was monitored throughout the experiment. The results showed that pretreatment of PLM to MI/R rats significantly reduced the incidence and duration of ventricular tachycardia and ventricular fibrillation. On induction of MI/R, the activities of creatine kinase and lactate dehydrogenase were increased in vehicle group. PLM (0.04-1.00 g/kg) administration prevented the increase of these enzymes. Moreover, a significant increase of myocardium superoxide dismutase and decrease of malondialdehyde contents were observed in rats of PLM groups. On the other hand, the expressions of platelet activating factor (PAF) receptor mRNA was down-regulated in a dose-dependent manner in the PLM-treated groups by RT-PCR. Thus, it can be concluded that pretreatment with PLM inhibited lipid peroxidation in rats through suppressing the expression of PAF receptor, which may contribute to its preventive effect on myocardial ischemia-reperfusion induced arrhythmias.

  14. Vascular endothelial growth factor induced angiogenesis following focal cerebral ischemia/reperfusion injury in rabbits

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    Huaijun Liu; Jiping Yang; Fenghai Liu; Qiang Zhang; Hui Li

    2006-01-01

    BACKGROUND: Therapeutic angiogenesis has opened up new pathway for the treatment of ischemic cerebrovascular disease in recent years. The exploration of the effect of vascular endothelial growth factor (VEGF) on inducing angiogenesis following ischemia/reperfusion injury can provide better help for the long-term treatment of cerebrovascular disease in clinic.OBJECTIVE: To observe the effect of VEGF on inducing angiogenesis following focal cerebral ischemia/reperfusion injury in rabbits through the angiogenesis of microvessels reflected by the expression of the factors of vascular pseudohemophilia.DESIGN: A randomized controlled animal trial.SETTING: Department of Medical Imaging, Second Hospital of Hebei Medical University.MATERIALS: Sixty-five healthy male New Zealand rabbits of clean degree, weighing (2.6±0.2) kg, aged4.5-5 months, were used. The polyclonal antibody against vascular pseudohemophilia (Beijing Zhongshan Company), recombinant VEGF165 (Peprotech Company, USA), biotinylated second antibody and ABC compound (Wuhan Boster Company) were applied.METHODS: The experiments were carried out in the Laboratory of Neuromolecular Imaging and Neuropathy,Second Hospital of Hebei Medical University from May to August in 2005. ① The rabbits were randomly divided into three groups: sham-operated group (n=15), control group (n=25) and VEGF-treated group(n=25). In the control group and VEGF-treated group, models were established by middle cerebral artery occlusion (MCAO) induced focal cerebral ischemia/reperfusion. In the VEGF-treated group, VEGF165(2.5 mg/L) was stereotactically injected into the surrounding regions of the infarcted sites immediately after the 2-hour ischemia/reperfusion; Saline of the same dosage was injected in the control group. But the rabobserved on the 3rd, 7th, 14th, 28th and 70th days of the experiment respectively, 3 rabbits in the sham-operated group and 5 in the control group and VEGF-treated group were observed at each time point. The

  15. Effects of transection of cervical sympathetic trunk on cerebral infarct volume and oxygen free radical levels in rats with focal cerebral ischemia/reperfusion injury

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    Liangzhi Xiong; Yongxia Shi; Feng Xiao; Qingxiu Wang

    2008-01-01

    BACKGROUND: Stellate ganglion block (SGB) plays a protective role on the brain, but the precise mechanism of action is not clear.OBJECTIVE: To simulate SGB by transection of the cervical sympathetic trunk (TCST) and to investigate the TCST effects on changes in cerebral infarct volume and oxygen free radical levels in rats with focal cerebral ischemia/reperfusion injury.DESIGN, TIME AND SETTING: A complete randomized control animal experiment was performed at the Institute of Neurological Diseases of Taihe Hospital, Yunyang Medical College from February to December 2005.MATERIALS: A total of 101 healthy Wistar rats, weighing 280-320g, of both genders, aged 17-18 weeks, were used in this study. 2,3,5-triphenyltetrazolium chloride (TTC) was purchased from Changsha Hongyuan Biological Company. Superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) assay kits were provided by Nanjing Jiancheng Bioengineering Institute.METHODS: Rats were randomly divided into a TCST group, a model group and a sham operation group. Successful models were included in the final analysis, with at least 20 rats in each group. After TCST, rat models of focal cerebral ischemia/reperfusion injury were established in the TCST group by receiving middle cerebral artery occlusion (MCAO) by the intraluminal suture method for 2 hours, followed by 24 hours of reperfusion. Rat models of focal cerebral ischemia/reperfusion injury were made in the model group. Rats in the sham operation group underwent experimental procedures as for the model group, threading depth of 10mm, and middle cerebral artery was not ligated.MAIN OUTCOME MEASURES: Brain tissue sections of ten rats from each group were used to measure cerebral infarct volume by TTC staining. Brain tissue homogenate of another ten rats from each group was used to detect SOD activities, MDA contents and NO levels. Rat neurological function was assessed by neurobehavioral measures.RESULTS: Cerebral infarct volume was bigger in the

  16. Protective role of fibrates in cardiac ischemia/reperfusion

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    G Singh

    2012-01-01

    Full Text Available Prevention of myocardial injury has been considered as the most important therapeutic challenge of today. Fibrates, the agonists of the peroxisome proliferator-activated receptor (PPAR-a receptor, have been regarded as potent therapeutic agents in this context. Hence, the present study has been designed to investigate the effect of fibrates, i.e., Clofibrate and Fenofibrate, the potent agonists PPAR-a, on ischemia-reperfusion (I/R-induced myocardial injury. The isolated Langendorff-perfused rat hearts were subjected to global ischemia for 30 minutes followed by reperfusion for 120 minutes. Myocardial infarct size and the release of lactate dehydrogenase (LDH and creatine kinase (CK in coronary effluent have been conducted to assess the degree of cardiac injury. Moreover, the oxidative stress in the heart was assessed by measuring lipid peroxidation, superoxide anion generation, and reduced glutathione. Clofibrate and Fenofibrate showed cardioprotection against I/R-induced myocardial injury in rat hearts as assessed in terms of reductions in myocardial infarct size, LDH, and CK levels in coronary effluent along with reduction in I/R-induced oxidative stress. It may be concluded that the observed cardioprotective potential of Clofibrate and Fenofibrate against I/R-induced myocardial injury was due to the reductions in infarct size and oxidative stress.

  17. Ablation of cereblon attenuates myocardial ischemia-reperfusion injury.

    Science.gov (United States)

    Kim, Jooyeon; Lee, Kwang Min; Park, Chul-Seung; Park, Woo Jin

    2014-05-16

    Cereblon (CRBN) was originally identified as a target protein for a mild type of mental retardation in humans. However, recent studies showed that CRBN acts as a negative regulator of AMP-activated protein kinase (AMPK) by binding directly to the AMPK catalytic subunit. Because AMPK is implicated in myocardial ischemia-reperfusion (I-R) injury, we reasoned that CRBN might play a role in the pathology of myocardial I-R through regulation of AMPK activity. To test this hypothesis, wild-type (WT) and crbn knockout (KO) mice were subjected to I-R (complete ligation of the coronary artery for 30 min followed by 24h of reperfusion). We found significantly smaller infarct sizes and less fibrosis in the hearts of KO mice than in those of WT mice. Apoptosis was also significantly reduced in the KO mice compared with that in WT mice, as shown by the reduced numbers of TUNEL-positive cells. In parallel, AMPK activity remained at normal levels in KO mice undergoing I-R, whereas it was significantly reduced in WT mice under the same conditions. In rat neonatal cardiomyocytes, overexpression of CRBN significantly reduced AMPK activity, as demonstrated by reductions in both phosphorylation levels of AMPK and the expression of its downstream target genes. Collectively, these data demonstrate that CRBN plays an important role in myocardial I-R injury through modulation of AMPK activity.

  18. Does Dexpantenol Protect the Kidney from Ischemia-Reperfusion Injury?

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    Sezen ÖZKISACIK

    2011-05-01

    Full Text Available OBJECTIVES: Tissue injury occurs following reperfusion after creation of ischemia. Plenty of chemical agents have been shown to protect from such an injury. We planned to evaluate the protective effect of dexpanthenol (dxp in ischemia-reperfusion injury. MATERIAL and METHODS: 24 adult rats were used and divided into 3 groups. A right nephrectomy was performed through a median laparotomy incision in all groups. Additionally, in group 1 (sham group, left nephrectomy was made 6 hours later without creation of ischemia. In group 2 (Saline group, the left kidney was left ischemic for 1 hour and reperfusion was established for 6 hours. Saline was administered intraperitoneally thirty minutes before creation of ischemia and just before reperfusion. In group 3 (Dexpanthenol group, the left kidney was left ischemic for 1 hour and reperfusion was established for 6 hours. Dxp (500 mg/kg was administered intraperitoneally thirty minutes before creation of ischemia and just before reperfusion. A left nephrectomy was performed at the end of the 6 hours of reperfusion. Nephrectomy specimens were histopathologically analysed for congestion, inflammation and necrosis. Tissue NO, glutathione reductase, catalase and MDA levels were measured. RESULTS: There was no significant differences between the groups histopathologically or biochemically. CONCLUSION: Dexpanthenol is the biologically active form of pantothenic acid and has an antioxidant effect. Our study was not in correlation with the literature regarding a protective effect of dxp on various organs via its antioxidant effect.

  19. Effects of ulinastatin on renal ischemia-reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Cong-cong CHEN; Zi-ming LIU; Hui-hua WANG; Wei HE; Yi WANG; Wei-dong WU

    2004-01-01

    AIM: To investigate the effect and possible mechanism of ulinastatin on renal ischemia-reperfusion injury in rats.METHODS: Male Sprague-Dawley rats were subjected to 45-min bilateral renal ischemia, treated with intravenously 12 500 U ulinastatin at 30 min prior to ischemia and at the beginning of reperfusion, compared with a nontreated group without ulinastatin and a sham-operation group without bilateral renal ischemia. After 0 h, 2 h, 6 h, 12 h, and 24 h of reperfusion, serum creatinine and blood urea nitrogen were measured for the assessment of renal function, renal sections were used for histologic grading of renal injury, for immunohistochemical localization of Bcl-2 and heat shock protein 70. Renal ultrastructure was observed through a transmission electron microscope.RESULTS: Ulinastatin significantly reduced the increase in blood urea nitrogen and creatinine produced by renal ischemia-reperfusion, suggesting an improvement in renal function. Ulinastatin reduced the histologic evidence of renal damage associated with ischemia-reperfusion and accompanied with an up-regulation in the expression of Bcl-2 protein, but it had no significent effect on the expression of HSP 70. Ulinastatin also significantly reduced kidney ultrastructure damage caused by renal ischemia-reperfusion. CONCLUSION: The protease inhibitor, ulinastatin,reduced the renal dysfunction and injury associated with ischemia-reperfusion of the kidney. The protective effect of ulinastatin might be associated with the up-regulation of Bcl-2 expression and the effect on membrane fragility.

  20. Role of Nuclear Factor kappaB in Intestine Injury Induced by Hepatic Ischemia Reperfusion

    Institute of Scientific and Technical Information of China (English)

    陈俊华; 王国斌

    2004-01-01

    Summary: The role of nuclear factor kappaB in intestine injury induced by hepatic ischemia reperfusion was investigated. Eighteen male Wistar rats were divided into 3 groups randomly: sham operation group (group A), hepatic ischemia reperfusion group (group B) and hepatic ischemia reperfusion plus pyrrolidine dithiocarbamate (PDTC) group (group C). The rats in group A were only subjected to laparotomy, those in group B underwent partial hepatic ischemia reperfusion (ischemia for 1 h and reperfusion for 2 h) and those in group C underwent the same procedure as that of group B but received PDTC 200 mg/kg i.v. before and after ischemia. After reperfusion, tissues of jejunum and venous blood were obtained for measurement of TNF-α, MDA and MPO. The levels of TNF-α in jejunum and venous blood, the levels of MPO in jejunum in group B were significantly higher than those in group A and group C (P<0.05). There was no significant different in the levels of MDA between group B and group C. The severity of histological intestinal injury in group B and group C was similar. Hepatic ischemia reperfusion caused intestine injury, NF-kappaB may play an important role in this course and the targeting of upstream components of the inflammatory response, such as NF-kappaB, may have important therapeutic applications.

  1. Role of morphine preconditioning and nitric oxide following brain ischemia reperfusion injury in mice

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    Maedeh Arabian

    2015-01-01

    Full Text Available Objective(s: Morphine dependence (MD potently protects heart against ischemia reperfusion (IR injury through specific signaling mechanisms, which are different from the pathways involved in acute morphine treatment or classical preconditioning. Since opioid receptor density changes post cerebral ischemia strongly correlated with brain histological damage, in the present study, we tried to elucidate the possible role of opioid receptors in IR injury among morphine-dependent mice. Materials and Methods: Accordingly, incremental doses (10 mg/kg/day to 30 mg/kg/day of morphine sulphate were subcutaneously administered for 5 days before global brain ischemia induction through bilateral common carotid artery occlusion. Animals were received naloxone (5 mg/kg or L-NAME (20 mg/kg 30 min after the last morphine dose. Twenty four hr after the ischemia induction, Retention trial of passive avoidance test and western blot analysis were done. histological analysis (TUNEL and NISSL staining performed 72 hr after ischemia. Results: MD improved post ischemia memory performance (P

  2. Spironolactone Effect in Hepatic Ischemia/Reperfusion Injury in Wistar Rats

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    Julio César Jiménez Pérez

    2016-01-01

    Full Text Available Introduction. Ischemia/reperfusion (IR injury, often associated with liver surgery, is an unresolved problem in the clinical practice. Spironolactone is an antagonist of aldosterone that has shown benefits over IR injury in several tissues, but its effects in hepatic IR are unknown. Objective. To evaluate the effect of spironolactone on IR-induced damage in liver. Materials and Methods. Total hepatic ischemia was induced in rats for 20 min followed by 60 min of reperfusion. Spironolactone was administered and hepatic injury, cytokine production, and oxidative stress were assessed. Results. After IR, increased transaminases levels and widespread acute inflammatory infiltrate, disorganization of hepatic hemorrhage trabeculae, and presence of apoptotic bodies were observed. Administration of SPI reduced biochemical and histological parameters of liver injury. SPI treatment increased IL-6 levels when compared with IR group but did not modify either IL-1β or TNF-α with respect to IR group. Regarding oxidative stress, increased levels of catalase activity were recorded in IR + SPI group in comparison with group without treatment, whereas MDA levels were similar in IR + SPI and IR groups. Conclusions. Spironolactone reduced the liver damage induced by IR, and this was associated with an increase in IL-6 production and catalase activity.

  3. Effect of the Discharging Rate on Ischemia-Reperfusion Inj ury in Bladder of Patients with Acute Urinary Retention%放尿速度对急性尿潴留患者膀胱缺血再灌注损伤的影响

    Institute of Scientific and Technical Information of China (English)

    陈桂君; 刘忆菁; 曹凤; 益雯艳

    2015-01-01

    Obj ective To observe the effect of the discharging rate on ischemia-reperfusion inj ury in bladder of patients with acute urinary retention.Methods By Convenience sampling,90 cases were randomly divided into ob-servation group A,observation group B and control group,with 30 cases in each group.Three different rates were set when discharging,and the urinary sample on before urination (T1),during urination (T2),600ml (T3),800 ml (T4)and 0.5h after urination (T5)were collected.According to the rate of discharging on acute urinary reten-tion.Clinical efficacies of 3 groups were observed,RBC、WBC in urine were observed before(T1)and after voiding (T2,T3,T4,T5).The isomorphic red blood cell,white blood cell,number of epithelial cells,heart rate and blood pressure were measured and compared among three groups of patients.Results The isomorphic red blood cell, white blood cell,number of epithelial cells at T2,T3 and T4 in observation group were less than which in control group(P0.05). Conclusion It is better to keep the discharge rate at 150ml/min,and the initial urination volume of 400 ml after acute urinary retention which can reduce the damage of bladder histocyte.%目的:了解放尿速度对急性尿潴留(actue urinary retention,AUR)患者膀胱缺血再灌注损伤的影响。方法便利抽样法选择,2014年6-12月在上海市第七人民医院泌尿外科门诊就诊的突发 AUR患者90例为研究对象,按就诊先后将其分为对照组、观察组 A、观察组 B 各30例,放尿时设置3种不同的流速,并在放尿前(T1),放尿400 ml(T2)、600 ml(T3)、800 ml(T4)时和停止放尿后0.5 h(T5)五个时间点留取尿标本,测量并比较3组患者的尿检镜下均一红细胞、白细胞及上皮细胞数、心率、血压。结果除T5时间点的上皮细胞数外,观察组患者5个时间点尿标本的镜下均一红细胞、白细胞及上皮细胞数及患者的均低于对照组(均P<0.05),差异有统计

  4. Effect of oxytocin on gastric ischemia-reperfusion injury in rats

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    ZHANG Wenwen; ZHANG Jianfu; XU Ming; ZHANG Yongmei

    2007-01-01

    The effect of peripherally administered oxytocin (OT)on gastric ischemia-reperfusion injury(GI-RI)and its possible mechanism were investigated.The Sprague-Dawley (SD)rats were randomly divided into different treatment groups(n=6).The animal GI-RI model was established by clamping the celiac artery for 30 min to induce ischemia and then released to allow reperfusion for 1 h,and the degree of GI-RI was assessed by scoring the gastric mucosal damage index(GMDI),the gastric fluid output,gastric fluid output,gastric acidity were measured and the surgical preparations of vagotomy and sympathectomy were used to investigate the possible mechanism of OT on GI-RI.The results were as follows.Compared with the control group(NS plus GI-R only,GMDI 121.33±10.40,n=6),the intraperitoneal(ip)administration of oxytocin(20,100 μg/0.5 mL)obviously attenuated GI-RI(P<0.05),GMDI were 82.33±14.26,53.5±5.58 respectively(n=6);the gastric fluid output and the gastric acidity(evaluated by pH)of the control group were(430.17±87.36)μL,1.55±0.25(n=6),and those of the OT group were(102.45+48.00)μL,2.65+0.40(n=6)respectively;differences had statistical significance(P<0.01).The effect of oxytocin was reversed by atosiban,a selective oxytocin receptor antagonist.The GMDI of the group given atosiban 10 min before OT was 138.17±24.06(n=6),which had no significant difference with the control group.Oxytocin further attenuated GI-RI after vagotomy and sympathectomy(GMDI 6.83±8.89,29.67±5.54,n=6),compared with the GI-R group and the oxytocin group (P<0.01).These results indicated that the oxytocin could significantly protect gastric mucosal against injury induced by ischemia-reperfusion,and the oxytocin receptor was involved.This effect of oxytocin may be mediated through the vagus and sympathetic nerve,and then lead to the reduction of gastric juice output and the depression of gastric acidity.

  5. Methylprednisolone improves microcirculation in streptozotocin-induced diabetic rats after myocardial ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    HU Zhi-cheng; CHEN Yun-dai; REN Yi-hong

    2011-01-01

    Background Methylprednisolone has been demonstrated to decrease inflammation, and it may protect organs from ischemia/reperfusion (I/R) injury. This study aimed to investigate the effects of methylprednisolone on diabetic myocardial I/R injury.Methods Forty adult male Sprague-Dawley (SD) rats were randomized into five groups (n=8 in each group) including a sham operation (sham) group, I/R group, diabetic sham operation (DMS) group, diabetic I/R (DM-I/R) group and methylprednisolone intervention (MP+DM-I/R) group. The diabetic model was produced by injection of streptozotocin (STZ). Body weight and blood glucose levels were determined after diabetes was established. Twelve weeks after induction of diabetes, a segmental I/R of the heart was induced by occluding the left anterior descending artery for one hour and then three hours of reperfusion in the I/R, DM-I/R and MP+DM-I/R groups. Blood pressure and electrocardiogram were continuously recorded during the procedure. IL-1β, IL-6 and TNF-α were measured at certain time points during the surgery. After reperfusion, a microcirculation scan was performed; myocardial biomarkers and tissue structure were utilized to evaluate the reperfusion damage. Intercellular adhesion molecule (ICAM)-1 and NF-κBp65 expression were quantified by immunohistological staining. Total Toil-like receptor 4 (TLR4) and nuclear NF-κBp65 protein were determined by Western blotting.Results Twelve weeks after diabetes was established, blood glucose levels were elevated and body weights were lower in diabetic rats. After reperfusion, infarction size was increased, myocardial biomarkers and inflammatory cytokines levels were elevated. Microcirculation perfusion was significantly reduced in the DM-I/R group compared with the I/R group, however it was improved in the MP+DM-I/R group. The expression of NF-κBp65 and ICAM-1 were increased in the DM-I/R group and decreased in the MP+DM-I/R group, Compared with the non-diabetic I/R group, TLR4 and NF

  6. Ischemia/reperfusion-induced Kidney Injury in Heterozygous PACAP-deficient Mice.

    Science.gov (United States)

    Laszlo, E; Varga, A; Kovacs, K; Jancso, G; Kiss, P; Tamas, A; Szakaly, P; Fulop, B; Reglodi, D

    2015-09-01

    Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with very diverse distribution and functions. Among others, PACAP is a potent cytoprotective peptide due to its antiapoptotic, anti-inflammatory, and antioxidant actions. This also has been shown in different kidney pathologies, including ischemia/reperfusion-induced kidney injury. Similar protective effects of the endogenous PACAP are confirmed by the increased vulnerability of PACAP-deficient mice to different harmful stimuli. Kidneys of homozygous PACAP-deficient mice have more severe damages in renal ischemia/reperfusion and kidney cell cultures isolated from these mice show increased sensitivity to renal oxidative stress. In our present study we raised the question of whether the partial lack of the PACAP gene is also deleterious, i.e. whether heterozygous PACAP-deficient mice also display more severe damage after renal ischemia/reperfusion. Mice underwent 45 or 60 minutes of ischemia followed by 2 weeks reperfusion. Histological evaluation of the kidneys was performed and individual histopathological parameters were graded. Furthermore, we investigated apoptotic markers, cytokine expression, and the activity of superoxide dismutase (SOD) enzyme 24 hours after 60 minutes of renal ischemia/reperfusion. We found no difference between the intact kidneys of wild-type and heterozygous mice, but marked differences could be observed following ischemia/reperfusion. Heterozygous PACAP-deficient mice had more severe histological alterations, with significantly higher histopathological scores for most of the tested parameters. Higher level of the proapoptotic pp38 MAPK and of some proinflammatory cytokines, as well as lower activity of the antioxidant SOD could be found in these mice. In conclusion, the partial lack of the PACAP gene results in worse outcomes in cases of renal ischemia/reperfusion, confirming that PACAP functions as an endogenous protective factor in the kidney.

  7. Simvastatin inhibits inflammation in ischemia-reperfusion injury.

    Science.gov (United States)

    Zhao, Yilin; Feng, Qingzhao; Huang, Zhengjie; Li, Wenpeng; Chen, Baisheng; Jiang, Long; Wu, Binglin; Ding, Weiji; Xu, Gang; Pan, Heng; Wei, Wei; Luo, Weiyuan; Luo, Qi

    2014-10-01

    Ischemia/reperfusion (I/R) is associated with leukocyte accumulation and tissue injury. The aim of this research was to investigate the protective effect of simvastatin on hind limb I/R inflammation and tissue damage. Mice were subjected to hind limb ischemic insult for 2 h and were simultaneously administered an intraperitoneal injection of simvastatin (5 mg/kg); this was followed by 36 h of reperfusion. Myeloperoxidase (MPO) levels in the muscles of the hind limb were determined. CXC chemokines and pro-inflammatory cytokines, such as macrophage inflammatory protein (MIP)-2, cytokine-induced neutrophil chemoattractant (KC), interleukin (IL)-6, tumor necrosis factor (TNF)-α, and P-selectin, were assessed using enzyme-linked immunosorbent assay (ELISA). Leukocyte rolling and adhesion in vitro was assessed to indicate leukocyte recruitment at the site of inflammation. Quantitative measurement of skeletal muscle tissue injury was performed. The fluorescent dye level in tissue and serum was used to determine hind limb vascular leakage and tissue edema after I/R. Systemic and differentiated leukocytes were also counted. Simvastatin significantly reduced MIP-2, KC, TNF-α, MPO, IL-6, and P-selectin levels compared to the sham group and I/R plus pretreatment with phosphate-buffered saline (PBS) group (Pinflammation, vascular leakage, and muscular damage (P<0.05). Simvastatin also significantly inhibited leukocyte rolling and adhesion compared to PBS (P<0.05). Our results suggest that simvastatin may be an effective protectant against tissue injury associated with I/R.

  8. Ischemia/reperfusion injury in the rat colon.

    Science.gov (United States)

    Murthy, S; Hui-Qi, Q; Sakai, T; Depace, D E; Fondacaro, J D

    1997-04-01

    This study investigated metabolic and biochemical consequences of colonic ischemia/reperfusion (I/R) in the rat and evaluated whether antioxidants prevent I/R-induced functional damage in the rat colon. The surgical preparation involved a 10 cm segment of the colon and occlusion of the superior mesenteric artery (SMA) to induce I/R. Arterial blood from the aorta and venous blood from the superior mesenteric vein (SMV) was collected to measure blood gases, lactic acid (LA) and arachidonic acid (AA) metabolites. Tissue xanthine oxidase (XO) and thiobarbituric acid (TBA) derivatives were measured before and after reperfusion. In addition, vascular and mucosal permeability, and the effect of MDL 73404 (a water soluble vitamin E analog) and 5-aminosalicylic acid on LA, AA, XO and TBA was measured. After ischemia, the colon displayed a metabolic shift from aerobic to anaerobic course by increasing lactic acid production in the colon (183% increase in SMV lactate level compared 87% in the SMA; p < 0.03). After 10 minutes of reperfusion, circulating 6-keto-prostaglandin F1 alpha increased by 3.85 fold (p < 0.001) and thromboxane B2 increased by 2 to 3 fold. An Ischemia time longer than 60 minutes was required to cause changes in tissue XO levels. Tissue TBA levels showed a good dose response corresponding with I/R time. I/R (60 minutes) caused a three and 16 fold increase (p < 0.01) in vascular and mucosal permeability, respectively. MDL 73404 and 5-aminosalicylic acid significantly inhibited the vascular permeability and decreased LA, AA, XO and TBA. These observations provide the first direct experimental evidence for I/R-induced damage in the colon and some of its effects can be reversed by conventional and novel antioxidants.

  9. Renalase as a Novel Biomarker for Evaluating the Severity of Hepatic Ischemia-Reperfusion Injury

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    Huili Li

    2016-01-01

    Full Text Available Hepatic ischemia-reperfusion (I/R injury is a serious complication in clinical practice. However, no efficient biomarkers are available for the evaluation of the severity of I/R injury. Recently, renalase has been reported to be implicated in the I/R injury of various organs. This protein is secreted into the blood in response to increased oxidative stress. To investigate the responsiveness of renalase to oxidative stress, we examined the changes of renalase in cell and mouse models. We observed a significant increase of renalase expression in HepG2 cells in a time- and dose-dependent manner when treated with H2O2. Renalase expression also increased significantly in liver tissues that underwent the hepatic I/R process. The increased renalase levels could be efficiently suppressed by antioxidants in vitro and in vivo. Furthermore, serum renalase levels were significantly increased in the mouse models and also efficiently suppressed by antioxidants treatment. The variation trends are consistent between renalase and liver enzymes in the mouse models. In conclusion, renalase is highly sensitive and responsive to oxidative stress in vitro and in vivo. Moreover, renalase can be detected in the blood. These properties make renalase a highly promising biomarker for the evaluation of the severity of hepatic I/R injury.

  10. Repressor and activator protein accelerates hepatic ischemia reperfusion injury by promoting neutrophil inflammatory response.

    Science.gov (United States)

    Li, Chang Xian; Lo, Chung Mau; Lian, Qizhou; Ng, Kevin Tak-Pan; Liu, Xiao Bing; Ma, Yuen Yuen; Qi, Xiang; Yeung, Oscar Wai Ho; Tergaonkar, Vinay; Yang, Xin Xiang; Liu, Hui; Liu, Jiang; Shao, Yan; Man, Kwan

    2016-05-10

    Repressor and activator protein (Rap1) directly regulates nuclear factor-κB (NF-κB) dependent signaling, which contributes to hepatic IRI. We here intended to investigate the effect of Rap1 in hepatic ischemia reperfusion injury (IRI) and to explore the underlying mechanisms. The association of Rap1 expression with hepatic inflammatory response were investigated in both human and rat liver transplantation. The effect of Rap1 in hepatic IRI was studied in Rap1 knockout mice IRI model in vivo and primary cells in vitro. Our results showed that over expression of Rap1 was associated with severe liver graft inflammatory response, especially in living donor liver transplantation. The results were also validated in rat liver transplantation model. In mice hepatic IRI model, the knockout of Rap1 reduced hepatic damage and hepatic inflammatory response. In primary cells, the knockout of Rap1 suppressed neutrophils migration activity and adhesion in response to liver sinusoidal endothelial cells through down-regulating neutrophils F-Actin expression and CXCL2/CXCR2 pathway. In addition, the knockout of Rap1 also decreased production of pro-inflammatory cytokines/chemokines in primary neutrophils and neutrophils-induced hepatocyte damage. In conclusion, Rap1 may induce hepatic IRI through promoting neutrophils inflammatory response. Rap1 may be the potential therapeutic target of attenuating hepatic IRI.

  11. Curcumin reduces inflammatory reactions following transient cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Jing Zhao; Shanshan Yu; Lan Li; Xuemei Lin; Yong Zhao

    2011-01-01

    Inflammatory reactions are important pathophysiological mechanisms of ischemic brain injury. The present study analyzed the anti-inflammatory characteristics of curcumin via myeloperoxidase activity and nitric oxide content after 2-hour ischemia/24-hour reperfusion in Sprague Dawley rats. In addition, expressions of nuclear factor kappa B, tumor necrosis factor-α and interleukin-1β protein were measured. Curcumin significantly reduced myeloperoxidase and nitric oxide synthase activities and suppressed expressions of nuclear factor kappa B, tumor necrosis factor-a, and interleukin-1β in ischemia/reperfusion brain tissue. Results suggested that the neuroprotective effect of curcumin following cerebral ischemia/reperfusion injury could be associated with inhibition of inflammatory reactions.

  12. Protective effect of hypercapnic acidosis in ischemia-reperfusion lung injury is attributable to upregulation of heme oxygenase-1.

    Science.gov (United States)

    Wu, Shu-Yu; Li, Min-Hui; Ko, Fu-Chang; Wu, Geng-Chin; Huang, Kun-Lun; Chu, Shi-Jye

    2013-01-01

    Hypercapnic acidosis (HCA) has protective effects in animal models of acute lung injury, but the mechanism underlying the effect of HCA is unclear. Heme oxygenase-1 (HO-1) is an antioxidant enzyme that protects tissue from inflammation injury. We investigated whether HO-1 contributes to the protective effects of HCA in ischemia-reperfusion (IR)-induced lung injury. Typical acute lung injury in rats was successfully induced by 40 min of ischemia and 90 min of reperfusion in an isolated perfused lung model. The rat lungs were randomly assigned to the control group, IR group or IR + HCA group with or without zinc protoporphyrin IX (ZnPP), an HO-1 activity inhibitor. At the end of the experiment, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. In in vitro experiments, HO-1 siRNA transfected A549 cells were exposed to a normoxic or hypoxia-reoxygenation (H/R) environment in the presence or absence of HCA. IR caused significant increases in the pulmonary arterial pressure, lung weight to body weight and wet/dry ratios, lung weight gain, capillary filtration coefficient, lung injury scores, neutrophil infiltration, and concentrations of protein and TNF-α in the BALF. IR also induced degradation of inhibitor of nuclear factor (NF)-κB-α, increased IκB kinase (IKK)-β phosphorylation and nuclear translocation of NF-κB, and up-regulated HO-1 expression and activity. Furthermore, IR decreased Bcl-2 protein expression and increased the number of active caspase-3 stained cells. HCA treatment enhanced HO-1 expression and activity, and accordingly reduced IKK-NF-κB signaling, inhibited apoptosis, and significantly attenuated IR-induced changes. Treatment with ZnPP partially blocked the protective effect of HCA. In addition, HO-1 siRNA significantly reversed HCA-mediated inhibition of NF-κB signaling in A549 cells subjected to H/R. In conclusion, the protective effect of HCA in IR lung injury in rats was mediated in

  13. Protective effect of hypercapnic acidosis in ischemia-reperfusion lung injury is attributable to upregulation of heme oxygenase-1.

    Directory of Open Access Journals (Sweden)

    Shu-Yu Wu

    Full Text Available Hypercapnic acidosis (HCA has protective effects in animal models of acute lung injury, but the mechanism underlying the effect of HCA is unclear. Heme oxygenase-1 (HO-1 is an antioxidant enzyme that protects tissue from inflammation injury. We investigated whether HO-1 contributes to the protective effects of HCA in ischemia-reperfusion (IR-induced lung injury. Typical acute lung injury in rats was successfully induced by 40 min of ischemia and 90 min of reperfusion in an isolated perfused lung model. The rat lungs were randomly assigned to the control group, IR group or IR + HCA group with or without zinc protoporphyrin IX (ZnPP, an HO-1 activity inhibitor. At the end of the experiment, bronchoalveolar lavage fluid (BALF and lung tissues were collected to evaluate the degree of lung injury. In in vitro experiments, HO-1 siRNA transfected A549 cells were exposed to a normoxic or hypoxia-reoxygenation (H/R environment in the presence or absence of HCA. IR caused significant increases in the pulmonary arterial pressure, lung weight to body weight and wet/dry ratios, lung weight gain, capillary filtration coefficient, lung injury scores, neutrophil infiltration, and concentrations of protein and TNF-α in the BALF. IR also induced degradation of inhibitor of nuclear factor (NF-κB-α, increased IκB kinase (IKK-β phosphorylation and nuclear translocation of NF-κB, and up-regulated HO-1 expression and activity. Furthermore, IR decreased Bcl-2 protein expression and increased the number of active caspase-3 stained cells. HCA treatment enhanced HO-1 expression and activity, and accordingly reduced IKK-NF-κB signaling, inhibited apoptosis, and significantly attenuated IR-induced changes. Treatment with ZnPP partially blocked the protective effect of HCA. In addition, HO-1 siRNA significantly reversed HCA-mediated inhibition of NF-κB signaling in A549 cells subjected to H/R. In conclusion, the protective effect of HCA in IR lung injury in rats was

  14. Intermedin protects against myocardial ischemia-reperfusion injury in hyperlipidemia rats.

    Science.gov (United States)

    Yang, S M; Liu, J; Li, C X

    2014-10-20

    Hyperlipidemia is a well-established risk factor for the development of coronary atherosclerosis, while intermedin (IMD) has been identified as a novel calcitonin/calcitonin gene-related peptide family member involved in cardiovascular protection. However, whether IMD protects against hyperlipidemia-associated myocardial ischemia/reperfusion (MI/R) injury is unknown. We established a hyperlipidemia model using Sprague-Dawley rats, and created a MI/R condition by ligating the cardiac left circumflex artery. The possible pathophysiological role of IMD and its physiological function in MI/R was further studied. The level of IMD significantly decreased in hyperlipidemia rats (P hyperlipidemia rats compared to the sham-operated rats (P hyperlipidemia rats (P hyperlipidemia-associated MI/R injury. Additional IMD could protect cardiac myocytes against MI/R injury via reduction of apoptosis and inflammation in the hyperlipidemia rat model, and thus, it may play a potential role as a novel therapeutic target for cardiac ischemic injury in hyperlipidemic patients.

  15. Diannexin protects against renal ischemia reperfusion injury and targets phosphatidylserines in ischemic tissue.

    Directory of Open Access Journals (Sweden)

    Kimberley E Wever

    Full Text Available Renal ischemia/reperfusion injury (IRI frequently complicates shock, renal transplantation and cardiac and aortic surgery, and has prognostic significance. The translocation of phosphatidylserines to cell surfaces is an important pro-inflammatory signal for cell-stress after IRI. We hypothesized that shielding of exposed phosphatidylserines by the annexin A5 (ANXA5 homodimer Diannexin protects against renal IRI. Protective effects of Diannexin on the kidney were studied in a mouse model of mild renal IRI. Diannexin treatment before renal IRI decreased proximal tubule damage and leukocyte influx, decreased transcription and expression of renal injury markers Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 and improved renal function. A mouse model of ischemic hind limb exercise was used to assess Diannexin biodistribution and targeting. When comparing its biodistribution and elimination to ANXA5, Diannexin was found to have a distinct distribution pattern and longer blood half-life. Diannexin targeted specifically to the ischemic muscle and its affinity exceeded that of ANXA5. Targeting of both proteins was inhibited by pre-treatment with unlabeled ANXA5, suggesting that Diannexin targets specifically to ischemic tissues via phosphatidylserine-binding. This study emphasizes the importance of phosphatidylserine translocation in the pathophysiology of IRI. We show for the first time that Diannexin protects against renal IRI, making it a promising therapeutic tool to prevent IRI in a clinical setting. Our results indicate that Diannexin is a potential new imaging agent for the study of phosphatidylserine-exposing organs in vivo.

  16. Role of mucus in gastric mucosal injury induced by local ischemia/reperfusion.

    Science.gov (United States)

    Seno, K; Joh, T; Yokoyama, Y; Itoh, M

    1995-09-01

    The role of gastric mucus was evaluated in a rat model of gastric epithelial damage induced by local ischemia/reperfusion (I/R) stress. In this model, blood-to-lumen chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) clearance served as an index of injury. Tetraprenyl acetone (TPA; 100 mg, 200 mg/kg IP) was used to stimulate mucus production. Administration of TPA increased both the hexosamine content in gastric tissue and the amount of alcian blue-periodic acid Schiff (AB-PAS) stained mucus in the mucosa in a dose-dependent manner. Increases in 51Cr-EDTA clearance induced by I/R were significantly attenuated by TPA in a dose-dependent manner. N-acetyl-L-cysteine (NAC; 0.6%, 0.8%) was perfused into the gastric lumen to assess the effect of reduction in mucus on the injury induced by I/R. Although mean values of hexosamine content were increased by perfusion with NAC, AB-PAS-stained mucus in the mucosa was significantly decreased in a dose-dependent manner. Perfusion of NAC did not change basal 51Cr-EDTA clearance but significantly exacerbated the increase in clearance induced by I/R in a dose-dependent manner. These results indicate that gastric mucus protects the gastric mucosa against I/R stress in vivo.

  17. Inhibition of vascular peroxidase alleviates cardiac dysfunction and apoptosis induced by ischemia-reperfusion.

    Science.gov (United States)

    Li, Ting-Ting; Zhang, Yi-Shuai; He, Lan; Liu, Bin; Shi, Rui-Zheng; Zhang, Guo-Gang; Peng, Jun

    2012-07-01

    Myeloperoxidase (MPO) is involved in myocardial ischemia-reperfusion (IR) injury and vascular peroxidase (VPO) is a newly identified isoform of MPO. This study was conducted to explore whether VPO is involved in IR-induced cardiac dysfunction and apoptosis. In a rat Langendorff model of myocardial IR, the cardiac function parameters (left ventricular pressure and the maximum derivatives of left ventricular pressure and coronary flow), creatine kinase (CK) activity, apoptosis, VPO1 activity were measured. In a cell (rat-heart-derived H9c2 cells) model of hypoxia-reoxygenation (HR), apoptosis, VPO activity, and VPO1 mRNA expression were examined. In isolated heart, IR caused a marked decrease in cardiac function and a significant increase in apoptosis, CK, and VPO activity. These effects were attenuated by pharmacologic inhibition of VPO. In vitro, pharmacologic inhibition of VPO activity or silencing of VPO1 expression significantly suppressed HR-induced cellular apoptosis. Our results suggest that increased VPO activity contributes to IR-induced cardiac dysfunction and inhibition of VPO activity may have the potential clinical value in protecting the myocardium against IR injury.

  18. Electro-acupuncture for STAT3 expression and nuclear translocation in hippocampal tissues of rats following cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Lihong Kong; Xiaoling Zeng; Guojie Sun; Shenghong Liu

    2006-01-01

    BACKGROUND: It has been found in recent years that STATS widely distributes in nervous system, including hippocampal CA1-3 region, dentate gyrus and cerebral neocortex, etc. Ischemic brain injury can cause the release of some cytokines and growth factors, while electro-acupuncture may have multi-level, multi-channel and multi-target protective and interventional effects on ischemic brain injury.OBJ ECTIVE: To observe the effects of electro-acupuncture on STAT3 expression and nuclear translocation in hippocampal CA1 region of rat models of brain ischemia/reperfusion.DESIGN: Randomized and controlled observation.SETTING: Staff Room of Acupuncture and Moxibustion, Department of Acupuncture and Bone Injury,Hubei College of Traditional Chinese Medicine; Tongji Medical College, Huazhong University of Science and Technology.MATERTALS: Seventy-two healthy SD rats, of clean degree and either gender, weighing (200±20) g, were provided by the Experimental Animal Center of Hubei College of Traditional Chinese Medicine. STAT3monoclonal antibody was purchased from Santa Cruz Company, USA, and G-6805 electro-acupuncture instrument was purchased from Shanghai Medical Electronic Instruments Factory.METHODS: This experiment was carried out in the comprehensive laboratory of Department of Acupuncture and Bone Injury, Hubei College of Traditional Chinese Medicine between September 2005 and February 2006.Seventy-two rats were randomly divided into 4 groups: ① control group(n =6): Untouched. ② Sham-operation group (n =18): Artery was isolated, but without inserting thread bolt.③ Model group (n =24): Rat models of local brain ischemia/reperfusion were established with modified suture occlusion. ④Electro-acupuncture group (n =24): Dazhui and bilateral Neiguan points were selected for electro-acupuncture treatment. No. 28acupuncture needle of 3.33 cm was used in the treatment A G-6085 electro-acupuncture instrument with continuous wave, frequency of 120 times/min, intensity of 1 m

  19. 丹参酮ⅡA对早期脑缺血和脑缺血再灌注损伤的脑保护作用%Neuroprotective effect of Tanshinone ⅡA on early cerebral ischemia and cerebral ischemia-reperfusion models

    Institute of Scientific and Technical Information of China (English)

    韩若东; 汤其强; 肖晗; 李俊

    2012-01-01

    目的 观察丹参酮ⅡA对大鼠早期脑缺血和脑缺血再灌注模型的脑保护作用及可能机制.方法 SD大鼠随机分为5组:假手术组、脑缺血2 h模型组、脑缺血2 h再灌注1 h模型组、脑缺血2 h+丹参酮ⅡA组、脑缺血2 h再灌注1 h+丹参酮ⅡA组.丹参酮ⅡA 以30 mg/kg灌胃,1次/d,假手术组、模型组用羧基纤维素钠代替.给药7 d后线栓法致大脑中动脉闭塞(MCAO)制备大鼠局灶性脑缺血再灌注模型.观察各组大鼠神经行为学评分(NBS),TUNEL法检测脑细胞凋亡,Western blot法检测脑梗死区Bax、Bcl-2的表达,TTC染色法检测脑梗死体积,试剂盒检测脑梗死区谷胱甘肽过氧化物酶(GSH-Px)的活性及丙二醛(MDA)含量.结果 与模型组比较,丹参酮ⅡA能明显降低梗死侧脑组织的细胞凋亡、脑梗死体积及Bax的表达,并能提高NBS评分、增加GSH-Px的活性及Bcl-2的表达,但对MDA含量无明显影响.结论 丹参酮ⅡA对大鼠早期脑缺血和脑缺血再灌注损伤具有脑保护作用,其机制可能是通过上调Bcl-2的表达、下调Bax的表达,增加GSH-Px的活性清除氧自由基,从而抑制细胞凋亡降低脑梗死体积,改善神经功能缺损评分.%Objective To observe the neuroprotection of Tanshinone IIA and its possible mechanisms on rat early cerebral ischemia and ischemia-reperfusion. Methods SD rats were randomly divided into five groups: sham group, ischemia for 2 h group, ischemia for 2 h/reperfusion for 1 h group, ischemia for 2 h + Tanshinone IIA 30 mg/kg administered and ischemia for 2 h/reperfusion for 1 h + Tanshinone IIA 30 mg/kg administered. Tanshinone IIA was gavaged once a day. Sham group and model group were gavaged sodium carboxymethyl cellulose as a substitute. After administration for 7 days, suture method induced by middle cerebral artery occlusion( MCAO ) to prepare focal cerebral ischemia and ischemia-reperfusion model. Neurobehavioral score( NBS ) was evaluated in each group

  20. Persistent HIF-1alpha activation in gut ischemia/reperfusion injury: potential role of bacteria and lipopolysaccharide.

    Science.gov (United States)

    Koury, Jadd; Deitch, Edwin A; Homma, Hiroshi; Abungu, Billy; Gangurde, Pranoti; Condon, Michael R; Lu, Qi; Xu, Da-Zhong; Feinman, Rena

    2004-09-01

    In both animal models of hemorrhagic shock and clinical settings, shock-induced gut ischemia has been implicated in the development of the systemic inflammatory response syndrome and distant organ injury, yet the factors transducing these events remain to be fully determined. Because hypoxia-inducible factor (HIF-1), a transcription factor composed of oxygen-labile HIF-1alpha and constitutive HIF-1beta subunits, regulates the physiologic/pathophysiologic response to hypoxia and ischemia, we examined the HIF-1 response in two rat models of gut ischemia-reperfusion. We found that ileal nuclear HIF-1alpha protein levels were induced in rats subjected to trauma (laparotomy) plus hemorrhagic shock for 90 min relative to their trauma sham-shock and naïve counterparts and that this trauma hemorrhagic shock-induced mucosal HIF-1alpha protein response persisted after 1 h and 3 h of reperfusion. Likewise, in a model of isolated gut ischemia-reperfusion injury, where the superior mesenteric artery was occluded for 45 min, nuclear HIF-1alpha were induced in the gut mucosa relative to their sham counterparts and persisted after 1 h and 3 h or reperfusion. Similar to the in vivo response, in vitro hypoxia induced HIF-alpha expression in three different enterocyte cell lines (rat IEC-6 and human Caco-2 and HT-29 cell lines). However, in contrast to the in vivo response, HIF-1 expression rapidly disappeared on subsequent reoxygenation. Because in vivo enterocytes are exposed to bacteria, we tested whether the in vitro HIF-1alpha response would persist on reoxygenation if the enterocytes were cocultured with bacteria. P. aeruginosa, an enteric bacterium, markedly induced enterocyte HIF-1alpha protein levels under normoxic conditions. Furthermore, the addition of P. aeruginosa during either the hypoxic or reoxygenation phase prevented the degradation of HIF-1alpha protein levels. Moreover, the observation that lipopolysaccharide induced HIF-1alpha expression in a time

  1. 匹伐他汀预处理对大鼠心肌缺血再灌注后炎性因子及氧化应激的影响%Effects of pitavastatin on inflammatory factors and the role of oxidative stress in a rat model of myocardial ischemia-reperfusion

    Institute of Scientific and Technical Information of China (English)

    尤杨; 戚国庆; 夏岳; 冯倩; 张庆文; 杨志瑜

    2014-01-01

    目的:探讨匹伐他汀预处理对大鼠急性心肌缺血再灌注后炎性因子及抗氧化物酶活性、心肌梗死面积的影响。方法成年雄性SD大鼠42只随机分为假手术组( Sham组)、对照组( I/R组)及实验组( Statin组),每组14只。 Sham组与I/R组术前给予生理盐水2 ml/d灌胃4周,Statin组给予匹伐他汀0�.42 mg· kg-1· d-1,溶解成2 ml灌胃4周。术后检测血清中白细胞介素-6(IL-6)、IL-26、肿瘤坏死因子(TNF)-α及磷酸肌酸激酶同工酶(CK-MB)的水平,留取结扎线下部分心肌组织用黄嘌呤氧化酶法测心肌总超氧化物岐化酶( T-SOD)活性,用氯化三苯基四氮唑( TTC)、伊文氏蓝( Evans blue )双染色法测定各组心肌梗死面积及缺血区面积。结果与I/R组比较,Statin组心肌梗死面积(AN/AAR)明显减少( P <0.01);与Sham组相比,I/R组、Statin组的血清IL-6、IL-26、TNF-α及CK-MB含量显著升高( P <0.01),T-SOD 含量下降( P <0.01);与I/R组比较,Statin 组 IL-6、IL-26、TNF-α及 CK-MB含量较低(P <0.05),T-SOD含量较高( P <0.01)。结论匹伐他汀可有效抑制炎性介质释放,提高机体抗氧化能力,减少心肌细胞坏死数量,减轻再灌注后心肌坏死程度,对预防缺血再灌注心肌损伤有积极作用。%Objective To explore the effects of pitavastain on inflammatory factors ( IL-6,IL-26,TNF-α) and T-SOD and cardiac infarct area in a rat model of myocardial ischemia-reperfusion , which will provide a theoretical basis for pitavastain clinical application in myocardial ischemia-reperfusion .Methods A total of 42 male SD rats were randomly assigned to three groups:Sham group , control group ( I/R group ) and experimental group ( Statin group ) .In Sham group and control group , 2ml saline were irrigated into stomach daily for 4 weeks, 0.42mg/kg pitavastain dissolved in 2ml saline were given

  2. Effects of pitavastatin on role of oxidative stress in a rat model of myocardial ischemia-reperfusion%匹伐他汀对大鼠心肌缺血再灌注后氧化应激作用的影响

    Institute of Scientific and Technical Information of China (English)

    尤杨; 冯倩; 夏岳; 戚国庆; 张燕; 张庆文

    2015-01-01

    Objective To explore the effects of pitavastain on the role of oxidative stress in a rat model of myocardial ischemia-reperfusion,which will provide a theoretical basis for pitavastain clinical application in myocardial ischemia-reperfusion.Methods A total of 42 male SD rats were randomly assigned to three groups:Sham group,control group (IR group)and experimental group(Statin group).In Sham group and control group,2 mL saline was irrigated into stomach daily for four weeks,0.42 mg/kg pitavastain dissolved in 2 mL saline was given in experimental group.In surgery,we wore line under the coronary artery without ligation in Sham group,and ligated the line for 30 minutes and then released it for 2 hours in IR group and Statin group.The levels of CK-MB were discerned after operation.Some myocardium tissue specimens under the line for ligation were used to detect the activity of total superoxide dismutase (T-SOD).The myocardial infarction size and risk area of each group were analyzed through comparing the differentiation of myocardium tissue stained by triphenyl tetrazolium chloride(TTC)and Evansblue by computer software system.Results The levels of CKMB elevated and TSOD contentdecreased significantly in control group and experimental group as compared with Sham group(P 0.05).Statin group significantlyreduced infarct size compared with IR group(P <0.01).Conclusion Pitavastatin could increaseantioxidant capacity and it took a positive role in ischemiareperfusion myocardial injuryprevention.%目的:探讨匹伐他汀对大鼠急性心肌缺血再灌注损伤(myocardial ischemia reperfusion inj ury,MIRI)的保护作用,为他汀类药物在缺血再灌注(ischemia reperfusion,IR)心肌的临床应用提供理论依据。方法将成年雄性 SD 大鼠42只随机分为假手术组(Sham 组)、IR 组及实验组(Statin 组)各14只。Sham 组与 IR 组术前给予生理盐水2 mL/d灌胃4周,Statin 组给予匹伐他汀0.42 mg·kg-1

  3. 门静脉淤血对肝脏缺血再灌注后肺脏和肾脏损伤的影响%The effect of portal blood stasis on lung and renal injury induced by hepatic ischemia reperfusion in a rabbit model

    Institute of Scientific and Technical Information of China (English)

    王野; 杨甲梅; 侯元凯; 李殿启; 胡明华; 刘鹏

    2008-01-01

    目的 探讨门静脉淤血对肝脏缺血再灌注后肺脏和肾脏损伤的影响及机制.方法 对24只新西兰大白兔行肝门阻断,同时经门静脉肝脏原位冷灌注30 min,恢复灌流时按门静脉淤血去除量的不同随机分为3组:A5组去除5 ml、A10组去除10 ml、B组不去除门静脉淤血,每组8只.另取8只作为对照(C组),仅行手术解剖,不做肝门阻断及肝脏灌注.检测去除门静脉淤血对恢复灌流4 h后血清内毒素、肿瘤坏死因子-α(TNF-α)、尿素氮(BUN)、肌酐(Cr)的影响;取肺脏、肾脏组织观察组织学改变并检测组织匀浆丙二醛(MDA)、超氧化物歧化酶(SOD)及肺湿/干重、肺灌洗液蛋白含量的变化.结果 去除门静脉淤血能降低复流后血清内毒素、TNF-α、BUN、Cr、肺湿/干重、肺灌洗液蛋白含量和肺脏、肾脏组织匀浆中MDA含量.其中A5组血清TNF-α、Cr、肺灌洗液蛋白含量、肾组织匀浆中MDA均明显低于B组(P<0.05);A10组血清内毒素、TNF-α肺湿/干重及肺组织匀浆中MDA也明显低于B组(P<0.05).去除门静脉淤血可增加肺脏、肾脏组织匀浆中SOD活性,其中A5组肾组织匀浆中SOD活性明显高于B组(P<0.05).同时,去除门静脉淤血能明显改善肺脏、肾脏组织学变化.结论 去除门静脉淤血可以减轻肝脏缺血再灌注后肺脏、肾脏功能的损伤,其机制可能与门静脉淤血去除减少内毒素吸收,进而降低了血清TNF-α产生有关.%Objective To investigate the effect and mechanism of portal blood stasis on lung and renal injury induced by hepatic ischemia reperfusion. Methods A rabbit hepatic ischemia reperfusion injury model was established by hepatic portal occlusion and in situ hypothermic irrigation for 30 min.Twenty-four New Zealand white rabbits were employed and randomly divided into 3 groups equally by different dosage of portal blood stasis removal:group A5(5 ml blood removal),group A10(10 ml blood removal),and group B

  4. Calreticulin Binds to Fas Ligand and Inhibits Neuronal Cell Apoptosis Induced by Ischemia-Reperfusion Injury

    Directory of Open Access Journals (Sweden)

    Beilei Chen

    2015-01-01

    Full Text Available Background. Calreticulin (CRT can bind to Fas ligand (FasL and inhibit Fas/FasL-mediated apoptosis of Jurkat T cells. However, its effect on neuronal cell apoptosis has not been investigated. Purpose. We aimed to evaluate the neuroprotective effect of CRT following ischemia-reperfusion injury (IRI. Methods. Mice underwent middle cerebral artery occlusion (MCAO and SH-SY5Y cells subjected to oxygen glucose deprivation (OGD were used as models for IRI. The CRT protein level was detected by Western blotting, and mRNA expression of CRT, caspase-3, and caspase-8 was measured by real-time PCR. Immunofluorescence was used to assess the localization of CRT and FasL. The interaction of CRT with FasL was verified by coimmunoprecipitation. SH-SY5Y cell viability was determined by MTT assay, and cell apoptosis was assessed by flow cytometry. The measurement of caspase-8 and caspase-3 activity was carried out using caspase activity assay kits. Results. After IRI, CRT was upregulated on the neuron surface and bound to FasL, leading to increased viability of OGD-exposed SH-SY5Y cells and decreased activity of caspase-8 and caspase-3. Conclusions. This study for the first time revealed that increased CRT inhibited Fas/FasL-mediated neuronal cell apoptosis during the early stage of ischemic stroke, suggesting it to be a potential protector activated soon after IRI.

  5. Effect of Nigella sativa on ischemia-reperfusion induced rat kidney damage

    Directory of Open Access Journals (Sweden)

    Shahrzad Havakhah

    2015-12-01

    Full Text Available Objective(s:There are a few previously reported studies about the effect of Nigella sativa oil on renal ischemia-reperfusion injury (IRI. The aim of the present study was to test the hypothesis whether pre- or post-treatment with N. sativa hydroalcoholic extract (NSE would reduce tissue injury and oxidative damages in a clinically relevant rat model of renal IRI.    Materials and Methods: IRI was induced by clamping of bilateral renal arteries for 40 min fallowed by reperfusion for 180 min. NSE was prepared in a Soxhlet extractor and administrated with doses of 150 mg/kg or 300 mg/kg at 1 hr before ischemia induction (P-150 and 300 or at the beginning of reperfusion phase (T-150 and 300, via jugular catheter intravenously. The kidneys were then removed and subjected to biochemical analysis, comet assay or histopathological examination. Results: The kidneys of untreated IRI rats had a higher histopathological score (P

  6. The effect of erythropoietin on platelet distribution width during ischemia reperfusion injury in rats

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    Constantinos Tsompos

    2014-04-01

    Full Text Available OBJECTIVE: Aim of this experiment study was the erythropoietin (Epo testing, on rat model and particularly on ischemia reperfusion protocol. The benefit or the non effect of that molecule was studied hematologically on platelet distribution width (PDW. METHODS: 40 rats were used of mean weight 247,7 gr. PDW was measured on these time points: on 60 min after reperfusion (groups A and C, and on 120 min after reperfusion (groups B and D, A and B without but C and D with Epo administration. RESULTS: Epo administration increased significantly the PDW levels by 0.22 % [0.034374 % - 0.4056259 %] (P= 0.0214, in accordance also with paired t-test (P= 0.0196, 2 reperfusion time decreased significantly the PDW levels by 0.27 % [-0.4483669 % - 0.0916332 %] (P= 0.0040, in accordance also with paired t-test (P= 0.0012, and 3 interaction of Epo administration and reperfusion time increased non significantly the PDW levels by 0.06 % [-0.054648 % - 0.1819207 %] (P= 0.0615. CONCLUSION: Epo administration has significant increasing short-term effects on PDW levels. However, reperfusion time attenuates significantly this effect. Their interaction seems to resemble the action of Epo administration. The following question is whether these PDW levels alterations are the cause or the result of diseases process modification.

  7. MG132 Inhibits Myocardial Ischemia-reperfusion Injury by Regulating Apoptotic Pathway

    Institute of Scientific and Technical Information of China (English)

    Dai Cuilian; Luo Kailiang; Chen Zhangrong

    2007-01-01

    Objectives To administrated proteasome inhibitor-MG-132 prior to reperfusion in rat myocardial ischemia-reperfusion model to determine whether MG-132 could reduce myocytic apoptosis. Methods and results MG-132 (0.75 mg/kg in 2 ml DMSO) injection 5 min prior to reperfusion resulted significant reduction of myocardial reperfusion injury. This effect was accompanied by reduced polymorphonuclear neutrophils(PMN) infiltration in myocardial region surrounding the myocardial infarct, reduced apoptosis in cardiac myocytes, reduced NF-κB activation, as determined by electron microscopy, histology, immunohistochemistry, the terminal deoxynucleotidyl transferase-mediated nick endlabeling (TUNEL) method, reverse transcription-polymerase chain reaction. Functional effects of MG-132 on PMN accumulation, activation of nuclear factor kappa B(p65 mRNA and protein levels ), and apoptosis were characterized in rat myocardial tissue. MG132 time-dependently inhibited myocardial p65 mRNA expression and reduced myocardial apoptotic index (AI) after reperfusion for 2 h, 6 h and 24 h ( P<0.01 ). Moreover, MG-132 time-dependently decreased Bax protein levels, while increased Bcl-2 protein levels in ischemic and reperfused myocardium ( P<0.05 ), its effect peaked after reperfusion for 24 h. Conclusions Our results demonstrate that MG-132 reduced myocardial reperfusion injury by inhibiting myosytic apoptotic cell death and blocking activation of NF-κB, down-regulating Bax expression and up-regulating Bcl-2 expression as well as elevating Bcl-2/Bax ratio.

  8. Expression profiles of microRNAs after focal cerebral ischemia/reperfusion injury in rats

    Institute of Scientific and Technical Information of China (English)

    Fengguo Zhai; Xiuping Zhang; Yue Guan; Xudong Yang; Yang Li; Gaochen Song; Lixin Guan

    2012-01-01

    Rat models of focal cerebral ischemia/reperfusion injury were established by occlusion of the middle cerebral artery. Microarray analysis showed that 24 hours after cerebral ischemia, there were nine up-regulated and 27 down-regulated microRNA genes in cortical tissue. Bioinformatic analysis showed that bcl-2 was the target gene of microRNA-384-5p and microRNA-494, and caspase-3 was the target gene of microRNA-129, microRNA-320 and microRNA-326. Real-time PCR and western blot analyses showed that 24 hours after cerebral ischemia, bcl-2 mRNA and protein levels in brain tissue were significantly decreased, while caspase-3 mRNA and protein levels were significantly increased. This suggests that following cerebral ischemia, differentially expressed microRNA-384-5p, microRNA-494, microRNA-320, microRNA-129 and microRNA-326 can regulate bcl-2 and caspase-3 expression in brain tissue.

  9. Inhibitory effect of zileuton on inflammatory injury to myocardium following ischemia/reperfusion in rats

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    Hua-di QIN

    2014-03-01

    Full Text Available Objective  To investigate the protective effect of zileuton, an inhibitor of 5-lipoxygenase (5-LO, on ischemia/ reperfusion (I/R injury of rat myocardium, and its probable mechanisms. Methods  Thirty female SD rats were randomly divided into 3 groups (10 each: sham group (S group, ischemic/reperfusion group (I/R group, and zileuton group (Z group. The I/ R model was reproduced by left anterior descending (LAD artery occlusion for 45min followed by 120-min reperfusion. To rats of Z group 3mg/kg zileuton was given 15min before ischemia. Animals were sacrificed after reperfusion. The degree of myocardial damage was determined by means of pathological examination. Myocardial apoptosis was identified by TUNEL assay. The levels of leukotriene B4 (LTB4, interleukin-1β (IL-1β and tumor necrosis factor-α (TNF-α in plasma were determined by ELISA; the distribution of 5-LO in neutrophils was determined by immunofluorescence and Western blotting. Results  Compared with I/ R group, zileuton attenuated the I/R-induced myocardial damage significantly. TUNEL assay demonstrated a significant decrease in myocardial apoptosis by zileuton (P0.05. Conclusion  Zileuton may protect myocardium from I/R injury in rats through suppressing myocardial apoptosis and inflammation by inhibiting the 5-LO activation and redistribution. DOI: 10.11855/j.issn.0577-7402.2014.03.05

  10. Allopurinol Protects against Ischemia/Reperfusion-Induced Injury in Rat Urinary Bladders

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    Ju-Hyun Shin

    2015-01-01

    Full Text Available Bladder ischemia-reperfusion (I/R injury results in the generation of reactive oxygen species (ROS and markedly elevates the risk of lower urinary tract symptoms (LUTS. Allopurinol is an inhibitor of xanthine oxidase (XO and thus can serve as an antioxidant that reduces oxidative stress. Here, a rat model was used to assess the ability of allopurinol treatment to ameliorate the deleterious effects of urinary bladder I/R injury. I/R injury reduced the in vitro contractile responses of longitudinal bladder strips, elevated XO activity in the plasma and bladder tissue, increased the bladder levels of tumor necrosis factor-α (TNF-α, c-Jun N-terminal kinase (JNK, and p38 mitogen-activated protein kinase, reduced the bladder levels of extracellular regulated kinase (ERK, and decreased and increased the bladder levels of Bcl-2 and Bax, respectively. I/R injury also elevated lipid peroxidation in the bladder. Allopurinol treatment in the I/R injury was generated significantly ameliorating all I/R-induced changes. Moreover, an in situ fluorohistological approach also showed that allopurinol reduces the generation of intracellular superoxides enlarged by I/R injury. Together, the beneficial effects of allopurinol reducing ROS production may be mediated by normalizing the activity of the ERK, JNK, and Bax/Bcl-2 pathways and by controlling TNF-α expression.

  11. Berberine alleviates cardiac ischemia/reperfusion injury by inhibiting excessive autophagy in cardiomyocytes.

    Science.gov (United States)

    Huang, Zhouqing; Han, Zhihua; Ye, Bozhi; Dai, Zhenyu; Shan, Peiren; Lu, Zhongqiu; Dai, Kezhi; Wang, Changqian; Huang, Weijian

    2015-09-05

    Ischemia/reperfusion (I/R)-induced autophagy increases the severity of cardiomyocyte injury. The aim of this study was to investigate the effects of berberine, a natural extract from Rhizoma coptidis, on the I/R-induced excessive autophagy in in vitro and in vivo models. Autophagy was increased both in H9c2 myocytes during hypoxia/reoxygenation (H/R) injury and in mouse hearts exposed to I/R. And the expression level of p-AMPK and p-mTORC2 (Ser2481) were increased during H/R period. In addition, the increased autophagy level was correlated with reduced cell survival in H9c2 myocytes and increased infarct size in mouse hearts. However, berberine treatment significantly enhanced the H/R-induced cell viability and reduced I/R-induced myocardial infarct size, which was accompanied by improved cardiac function. The beneficial effect of berberine is associated with inhibiting the cellular autophagy level, due to decreasing the expression level of autophagy-related proteins such as SIRT1, BNIP3, and Beclin-1. Furthermore, both the level of p-AMPK and p-mTORC2 (Ser2481) in H9c2 myocytes exposed to H/R were decreased by berberine. In summary, berberine protects myocytes during I/R injury through suppressing autophagy activation. Therefore, berberine may be a promising agent for treating I/R-induced cardiac myocyte injury.

  12. The Role of Tetrahydrobiopterin and Dihydrobiopterin in Ischemia/Reperfusion Injury When Given at Reperfusion

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    Qian Chen

    2010-01-01

    Full Text Available Reduced nitric oxide (NO bioavailability and increased oxidative stress are major factors mediating ischemia/reperfusion (I/R injury. Tetrahydrobiopterin (BH4 is an essential cofactor of endothelial NO synthase (eNOS to produce NO, whereas dihydrobiopterin (BH2 can shift the eNOS product profile from NO to superoxide, which is further converted to hydrogen peroxide (H2O2 and cause I/R injury. The effects of BH4 and BH2 on oxidative stress and postreperfused cardiac functions were examined in ex vivo myocardial and in vivo femoral I (20 min/R (45 min models. In femoral I/R, BH4 increased NO and decreased H2O2 releases relative to saline control, and these effects correlated with improved postreperfused cardiac function. By contrast, BH2 decreased NO release relative to the saline control, but increased H2O2 release similar to the saline control, and these effects correlated with compromised postreperfused cardiac function. In conclusion, these results suggest that promoting eNOS coupling to produce NO and decrease H2O2 may be a key mechanism to restore postreperfused organ function during early reperfusion.

  13. Ultrasound-enhanced protective effect of tetramethylpyrazine against cerebral ischemia/reperfusion injury.

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    Chunbing Zhang

    Full Text Available In traditional Chinese medicine, Ligusticum wallichii (Chuan Xiong and its bioactive ingredient, tetramethylpyrazine (TMP, have been used to treat cardiovascular diseases and to relieve various neurological symptoms, such as those associated with ischemic injury. In the present study, we investigated whether ultrasound (US exposure could enhance the protective effect of TMP against cerebral ischemia/reperfusion (I/R injury. Glutamate-induced toxicity to pheochromocytoma (PC12 cells was used to model I/R injury. TMP was paired with US to examine whether this combination could alleviate glutamate-induced cytotoxicity. The administration of TMP effectively protected cells against glutamate-induced apoptosis, which could be further enhanced by US-mediated sonoporation. The anti-apoptotic effect of TMP was associated with the inhibition of oxidative stress and a change in the levels of apoptosis-related proteins, Bcl-2 and Bax. Furthermore, TMP reduced the expression of proinflammatory cytokines such as TNF-α and IL-8, which likely also contributes to its cytoprotective effects. Taken together, our findings suggest that ultrasound-enhanced TMP treatment might be a promising therapeutic strategy for ischemic stroke. Further study is required to optimize ultrasound treatment parameters.

  14. A polysaccharide (PNPA) from Pleurotus nebrodensis offers cardiac protection against ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Yan, Bingju; Jing, Liying; Wang, Jun

    2015-11-20

    In this study, we isolated a polysaccharide (PNPA), with a molecular weight of 105kDa, from the fruiting bodies of Pleurotus nebrodensis. It had a backbone consisting of 1,3-linked-d-glucpyranosyl and 1,3,6-linked-d-galactopyranosyl residues, which was terminated with 1-linked-d-mannopyranosyl terminal at O-3 position of 1,3,6-linked-d-galactopyranosyl unit along the main chain in the ratio of 4:1:1. We further examined the effect of PNPA on myocardial ischemia-reperfusion (I/R) injury in rats and elucidated the underlying mechanism. Pretreatment with PNPA (100 and 400mg/kg) for 30 days significantly attenuated myocardial infarct size as compared to I/R model group. A decrease in superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels, as well as an increased malondialdehyde (MDA) content were observed in both myocardial serum and tissues of control I/R group, whereas pretreatment with PNPA markedly restored these change, and also relieved myocardial cell apoptosis. These results suggested that PNPA achieved protective effect on myocardial I/R injury in part through improving endogenous antioxidants and suppressing myocardial cell apoptosis.

  15. Comparative analysis of different cyclosporine A doses on protection after myocardial ischemia/reperfusion injury in rat

    Institute of Scientific and Technical Information of China (English)

    Kang Huang; Shi-Juan Lu; Jiang-Hua Zhong; Qun Xiang; Liu Wang; Miao Wu

    2014-01-01

    Objective:To investigate the protective effect of different cyclosporinA(CsA) doses on myocardial ischemia/reperfusion injury in rat models.Methods:A rat model of myocardial ischemia/reperfusion injury was established in vivoand the rats were randomly divided into four groups: placebo(PBS;T1), low-dose(CsA dose:1.0 mg/kg;T2), medium-dose(CsA dose:2.5 mg/kg;T3), and high-dose(CsA dose:5.0 mg/kg;T4) groups.Heart function indexes were monitored at different time points, the extent of myocardial infarction was assessed byEvans Blue-TTC staining, and creatine kinase MB mass and cardiac troponinI values were measured by biochemical assays.Results:Compared with theT1 andT2 groups, both the creatine kinase MB mass and cardiac troponinI were significantly lower in theT3 andT4 groups(P<0.05).The mean arterial pressure(MAP) and left ventricular systolic pressure(LVSP) decreased sequentially in each group, with the extending reperfusion time.Significant decreases inLVSP andMAP were observed in theT3 andT4 groups as compared to theT1 andT2 group(P<0.05), and theT2 group showed a significantly lowerLVSP andMAP decline than theT1 group(P<0.05).Compared with theT1 group, the rats from theT2,T3, andT4 groups suffered from a significantly lower extent of myocardial infarction(P<0.05).Also, the animals in theT3 andT4 groups had a significantly smaller extent of myocardial infarction than those in theT2 group(P<0.05).Conclusions:Various CsA doses exert different degrees of protection against ischemia/reperfusion injury, and this protective effect peaks at approximately2.5 mg/kg in rat models.

  16. Mechanism of the protective effects of noninvasive limbs preconditioning on myocardial ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiao-guang; WU Bin-yang; WANG Jun-ke; BAI Tao

    2005-01-01

    Background This study aimed at assessing the effect of noninvasive limb preconditioning on myocardial infarct size, and determining whether nitric oxide and neurogenic pathway play an important role in the mechanism of acute remote ischemic preconditioning (IPC).Methods Forty Wistar rats were randomly divided into four experimental groups. In Group Ⅰ, the rats underwent 30-minute occlusion of the left anterior descending coronary artery, and 120-minute reperfusion. In Group PL, the rats underwent four cycles of 5-minute occlusion and reperfusion of both hind limbs using a tourniquet before the experiment was continued as in Group Ⅰ. In Group PL-N and Group PL-H, we administered L-nitro-arginine methyl ester (L-NAME) 10 mg/kg or hexamethonium chloride 20 mg/kg intravenously, 10 minutes before IPC. Infarct size as a percentage of the area at risk was determined by triphenyltetrazolium chloride staining. Results There were no statistically significant differences in mean arterial pressure and heart rate among these groups at any time point during the experiment (P>0.05). The myocardial infarct size (IS) was decreased significantly in Group PL and Group PL-H compared with Group Ⅰ, and the IS/AAR was 34.5%±7.6%, 35.9%±8.6% and 58.5%±8.5%, respectively (P0.05).Conclusions Noninvasive limb IPC is effective in protecting the myocardium from ischemia reperfusion injury. Nitric oxide plays an important role in the mechanism of acute remote IPC, in which the neurogenic pathway is not involved.

  17. Soluble epoxide hydrolase activity determines the severity of ischemia-reperfusion injury in kidney.

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    Jung Pyo Lee

    Full Text Available Soluble epoxide hydrolase (sEH in endothelial cells determines the plasma concentrations of epoxyeicosatrienoic acids (EETs, which may act as vasoactive agents to control vascular tone. We hypothesized that the regulation of sEH activity may have a therapeutic value in preventing acute kidney injury by controlling the concentration of EETs. In this study, we therefore induced ischemia-reperfusion injury (IRI in C57BL/6 mice and controlled sEH activity by intraperitoneal administration of the sEH inhibitor 12-(3-adamantan-1-ylureido-dodecanoic acid (AUDA. The deterioration of kidney function induced by IRI was partially moderated and prevented by AUDA treatment. In addition, AUDA treatment significantly attenuated tubular necrosis induced by IRI. Ischemic injury induced the down-regulation of sEH, and AUDA administration had no effect on the expression pattern of sEH induced by IRI. In vivo sEH activity was assessed by measuring the substrate epoxyoctadecenoic acid (EpOME and its metabolite dihydroxyoctadec-12-enoic acid (DHOME. Ischemic injury had no effects on the plasma concentrations of EpOME and DHOME, but inhibition of sEH by AUDA significantly increased plasma EpOME and the EpOME/DHOME ratio. The protective effect of the sEH inhibitor was achieved by suppression of proinflammatory cytokines and up-regulation of regulatory cytokines. AUDA treatment prevented the intrarenal infiltration of inflammatory cells, but promoted endothelial cell migration and neovascularization. The results of this study suggest that treatment with sEH inhibitors can reduce acute kidney injury.

  18. The protective effect of erdosteine on short-term global brain ischemia/reperfusion injury in rats.

    Science.gov (United States)

    Ozerol, Elif; Bilgic, Sedat; Iraz, Mustafa; Cigli, Ahmet; Ilhan, Atilla; Akyol, Omer

    2009-02-01

    Experimental studies have demonstrated that free radicals play a major role on neuronal injury during ischemia/reperfusion (I/R) in rats. Erdosteine is a thioderivative endowed with mucokinetic, mucolytic and free-radical-scavenging properties. The aim of the present study was to investigate the effect of erdosteine treatment against short-term global brain ischemia/reperfusion injury in rats. The study was carried out on Wistar rats divided into four groups. (i) Control group, (ii) ischemia/reperfusion group, (iii) ischemia/reperfusion+erdosteine group, and (iv) erdosteine group. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities as well as thiobarbituric acid reactive substances (TBARSs) and nitric oxide (NO) levels were analysed in erythrocyte and plasma of rats. Plasma NO levels were significantly higher in the ischemia/reperfusion group than the other groups. The activities of SOD and GSH-Px were decreased, while TBARS levels increased in the ischemia/reperfusion group compared to other groups in both plasma and erythrocyte. The erythrocyte CAT activity was higher in erdosteine group and there was a statistically significant increase, when compared with the erdosteine plus ischemia/reperfusion group. By treating the rats with erdosteine, the depletion of endogenous antioxidant enzymes (SOD, CAT, GSH-Px) and increase of TBARS and NO levels were prevented. This study, therefore, suggests that erdosteine reduces parameters of oxidative stress is well supported by the data.

  19. Anisodamine augments mucosal blood flow during gut ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Hu Sen; Sheng Zhiyong

    2002-01-01

    Objective: To determine if anisodamine is able to augment mucosal perfusion during gut ischemia-reperfusion (I/R). Methods: A jejunal sac was formed in Sprague Dawley rat. A Laser Doppler probe and a tonometer were inserted into the sac which was filled with saline. The superior mesenteric artery was occluded (SMAO) for 60minutes followed by 90 minutes of reperfusion. At the end of 60 minutes of SMAO, either 0.2mg/kg of anisodmine or dobutamine was injected into the jejunal sac. Laser Doppler mucosal blood flow and regional PCO2 (PrCO2) measurements were made. Results: Mucosal blood flow was significantly increased at 30,60 and 90 minutes of reperfusion (R30, R60, R90 ) when intraluminal anisodamine or dobutamine was introduced compared to intraluminal saline only (44±3.3)% or (48±4.1)% vs. (37±2.6) % at R30, (57±5.0)% or (56±4.7)% vs. (45±2.7)% at R60, (64±3.3) % or (56 ± 4.2) % vs. (48 ± 3.4) % at R90 , respectively P<0.05). Blood flow changes were also reflected by lowering of jejunal PrCO2 measurements after intraluminal anisodamine or dobutamine compared with that of the saline controls (41±3. 1)mmHg or (44±3.0)mmHg vs. (49±3.7) mmHg at R30 , (38±3.7)mmHg or (40±2. 1)mmHg vs. (47±3.8) mmHgat R60, (34±2.1) mmHg or (39± 3.0) mmHg vs. (46±3.4) mmHg at R90, respectively,P<0. 05). The most interesting finding was that there were significantly higher mucosal blood flow and lower jejunal PrCO2 in anisodamine group than those in dobutamine group at 90 minutes of reperfusion (64± 3.3) %vs. (56±4.2)% for blood flow or (34 ± 2.1)mmHg vs. (39 ± 3.0)mmHg for PrCO2, respectively, P<0.05),suggesting that anisodamine had more lasting effect on mucosal perfusion than dobutamine. Conclusions:Intraluminal anisodamine can augment mucosal blood flow during gut I/R, and it may provide the protective effect on gut from ischemia and reperfusion injury.

  20. Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Xing-miao CHEN; Han-sen CHEN; Ming-jing XU; Jian-gang SHEN

    2013-01-01

    Ischemic stroke accounts for nearly 80% of stroke cases.Recanalization with thrombolysis is a currently crucial therapeutic strategy for re-building blood supply,but the thrombolytic therapy often companies with cerebral ischemia-reperfusion injury,which are mediated by free radicals.As an important component of free radicals,reactive nitrogen species (RNS),including nitric oxide (NO) and peroxynitrite (ONO0ˉ),play important roles in the process of cerebral ischemia-reperfusion injury.Ischemia-reperfusion results in the production of nitric oxide (NO) and peroxynitrite (ONOOˉ) in ischemic brain,which trigger numerous molecular cascades and lead to disruption of the blood brain barrier and exacerbate brain damage.There are few therapeutic strategies available for saving ischemic brains and preventing the subsequent brain damage.Recent evidence suggests that RNS could be a therapeutic target for the treatment of cerebral ischemia-reperfusion injury.Herein,we reviewed the recent progress regarding the roles of RNS in the process of cerebral ischemic-reperfusion injury and discussed the potentials of drug development that target NO and ONO0ˉ to treat ischemic stroke.We conclude that modulation for RNS level could be an important therapeutic strategy for preventing cerebral ischemiareperfusion injury.

  1. The antiendotoxin agent taurolidine potentially reduces ischemia/reperfusion injury through its metabolite taurine.

    LENUS (Irish Health Repository)

    Doddakula, Kishore K

    2010-09-01

    Cardiopulmonary bypass results in ischemia\\/reperfusion (I\\/R)-induced endotoxemia. We conducted a prospective randomized trial to investigate the effect of taurolidine, an antiendotoxin agent with antioxidant and membrane-stabilizing properties, on patients undergoing coronary artery bypass grafting (CABG).

  2. Protective function of tocilizumab in human cardiac myocytes ischemia reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Hai-Feng Cheng; Yan Feng; Da-Ming Jiang; Kai-Yu Tao; Min-Jian Kong

    2015-01-01

    Objective:To investigate the protective function of tocilizumab in human cardiac myocytes ischemia-reperfusion injury.Methods:The human cardiac myocytes were treated by tocilizumab with different concentrations(1.0 mg/mL, 3.0 mg/mL, 5.0 mg/mL) for 24 h,then cells were cultured in ischemia environment for 24 h and reperfusion environment for 1 h. The MTT and flow cytometry were used to detect the proliferation and apoptosis of human cardiac myocytes, respectively. The mRNA and protein expressions of Bcl-2 and Bax were measured by qRT-PCR and western blot, respectively.Results:Compared to the negative group, pretreated by tocilizumab could significantly enhance the proliferation viability and suppress apoptosis of human cardiac myocytes after suffering ischemia reperfusion injury(P<0.05).The expression of Bcl-2 in tocilizumab treated group were higher thanNC group(P<0.05), while theBax expression were lower(P<0.05).Conclusions:Tocilizumab could significantly inhibit apoptosis and keep the proliferation viability of human cardiac myocytes after suffering ischemia reperfusion injury. Tocilizumab may obtain a widely application in the protection of ischemia reperfusion injury.

  3. Preoperative fasting protects against renal ischemia-reperfusion injury in aged and overweight mice

    NARCIS (Netherlands)

    F. Jongbloed (Franny); R.W.F. de Bruin (Ron); J.L.A. Pennings (Jeroen); C. Payan-Gomez; S. van den Engel (Sandra); C.T.M. van Oostrom (Conny); A. de Bruin (Alain); J.H.J. Hoeijmakers (Jan); H. van Steeg (Harry); J.N.M. IJzermans (Jan); M.E.T. Dollé (Martijn)

    2014-01-01

    textabstractIschemia-reperfusion injury (IRI) is inevitable during kidney transplantation leading to oxidative stress and inflammation. We previously reported that preoperative fasting in young-lean male mice protects against IRI. Since patients are generally of older age with morbidities possibly l

  4. Therapeutic potential of cannabidiol against ischemia/reperfusion liver injury in rats.

    Science.gov (United States)

    Fouad, Amr A; Jresat, Iyad

    2011-11-16

    The therapeutic potential of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated in rats exposed to ischemia/reperfusion liver injury. Ischemia was induced by clamping the pedicle of the left hepatic lobe for 30 min, and cannabidiol (5mg/kg, i.v.) was given 1h following the procedure and every 24h thereafter for 2 days. Ischemia/reperfusion caused significant elevations of serum alanine aminotransferase and hepatic malondialdehyde, tumor necrosis factor-α and nitric oxide levels, associated with significant decrease in hepatic reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters mediated by ischemia/reperfusion. Histopathological examination showed that cannabidiol ameliorated ischemia/reperfusion-induced liver damage. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin protein in ischemic/reperfused liver tissue. These results emphasize that cannabidiol represents a potential therapeutic option to protect the liver against hypoxia-reoxygenation injury.

  5. NADPH oxidase inhibitor apocynin attenuates ischemia/reperfusion induced myocardial injury in rats

    Institute of Scientific and Technical Information of China (English)

    罗秀菊

    2013-01-01

    Objective To explore the role of NADPH oxidase inhibitor apocynin on ischemia/reperfusion(I/R)-induced myocardial injury. Methods Male SD rat hearts were divided into the normal control group; sham group;I/R group(1 h ischemia followed by 3 h reperfusion); I/R+ apocynin group(50 mg/kg,administrated at 30 min

  6. MRI of renal oxygenation and function after normothermic ischemia-reperfusion injury

    NARCIS (Netherlands)

    Oostendorp, M. van; Vries, E.E. de; Slenter, J.M.; Peutz-Kootstra, C.J.; Snoeijs, M.G.; Post, M.J.; Heurn, L.W. van; Backes, W.H.

    2011-01-01

    The in vivo assessment of renal damage after ischemia-reperfusion injury, such as in sepsis, hypovolemic shock or after transplantation, is a major challenge. This injury often results in temporary or permanent nonfunction. In order to improve the clinical outcome of the kidneys, novel therapies are

  7. Preoperative fasting protects against renal ischemia-reperfusion injury in aged and overweight mice

    NARCIS (Netherlands)

    Jongbloed, Franny; De Bruin, Ron W F; Pennings, Jeroen L A; Payán-Gómez, César; Van Den Engel, Sandra; Van Oostrom, Conny T.; De Bruin, Alain; Hoeijmakers, Jan H J; Van Steeg, Harry; IJzermans, Jan N M; Dollé, Martijn E T

    2014-01-01

    Ischemia-reperfusion injury (IRI) is inevitable during kidney transplantation leading to oxidative stress and inflammation. We previously reported that preoperative fasting in young-lean male mice protects against IRI. Since patients are generally of older age with morbidities possibly leading to a

  8. Protective effects of amifostine on ischemia-reperfusion injury of rat kidneys

    Directory of Open Access Journals (Sweden)

    Ayse Arducoglu Merter

    2015-01-01

    Conclusion: Amifostine could decrease the degree and severity of necrosis after reperfusion. Amifostine could not prevent membrane lipid peroxidation caused by superoxide anion radicals in kidney but they could protect tissues from the harmful effects of ischemia/reperfusion injury by increasing the level of reduced GSH which is a well-known oxygen radical eliminator.

  9. Effect of tramadol on lung injury induced by skeletal muscle ischemia-reperfusion: an experimental study

    Directory of Open Access Journals (Sweden)

    Mohammad Ashrafzadeh Takhtfooladi

    2013-06-01

    Full Text Available OBJECTIVE: To determine whether tramadol has a protective effect against lung injury induced by skeletal muscle ischemia-reperfusion. METHODS: Twenty Wistar male rats were allocated to one of two groups: ischemia-reperfusion (IR and ischemia-reperfusion + tramadol (IR+T. The animals were anesthetized with intramuscular injections of ketamine and xylazine (50 mg/kg and 10 mg/kg, respectively. All of the animals underwent 2-h ischemia by occlusion of the femoral artery and 24-h reperfusion. Prior to the occlusion of the femoral artery, 250 IU heparin were administered via the jugular vein in order to prevent clotting. The rats in the IR+T group were treated with tramadol (20 mg/kg i.v. immediately before reperfusion. After the reperfusion period, the animals were euthanized with pentobarbital (300 mg/kg i.p., the lungs were carefully removed, and specimens were properly prepared for histopathological and biochemical studies. RESULTS: Myeloperoxidase activity and nitric oxide levels were significantly higher in the IR group than in the IR+T group (p = 0.001 for both. Histological abnormalities, such as intra-alveolar edema, intra-alveolar hemorrhage, and neutrophil infiltration, were significantly more common in the IR group than in the IR+T group. CONCLUSIONS: On the basis of our histological and biochemical findings, we conclude that tramadol prevents lung tissue injury after skeletal muscle ischemia-reperfusion.

  10. 76 FR 42716 - Effects of Ischemia Reperfusion Injury on Outcomes in Kidney Transplantation; Public Workshop

    Science.gov (United States)

    2011-07-19

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Effects of Ischemia Reperfusion Injury on Outcomes in Kidney... Food and Drug Administration (FDA) is announcing a public workshop to discuss the effects of...

  11. Marginal Copper Deficiency Increases Liver Neutrophil Accumulation After Ischemia/Reperfusion in Rats

    Science.gov (United States)

    Copper deficiency can lead to an augmented inflammatory response through effects on both neutrophils and the microvascular endothelium. In the present study, we evaluated the effect of marginal copper deficiency on the inflammatory injury response to hepatic ischemia/reperfusion injury. Male weanlin...

  12. Ischemia-Reperfusion Injury : Maintaining skeletal muscle function and vasomotor control

    NARCIS (Netherlands)

    With, M.C.J. de

    2009-01-01

    In reconstructive surgery, ischemia-reperfusion (I-R) injury of skeletal muscle tissue occurs during replantations, free vascularized transfers of muscle flaps and following composite tissue allograft (CTA) transplantations. The latter is a newly emerging field and involves the allotransplantation o

  13. Protective effects of acupuncture on brain tissue following ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Mingshan Wang; Fuguo Ma; Huailong Chen

    2008-01-01

    BACKGROUND: In patients with cerebrovascular disease, by means of the neuroendocrine system, acupuncture supports the transformation of a local pathological status into a physiological status. Recently, great progress has been made in studying the protective effects of acupuncture on brain ischemia/reperfusion injury. OBJECTIVE: To summarize research advances in the protective effects of acupuncture on brain ischemia/reperfusion injury. RETRIEVAL STRATEGY: Using the terms "acupuncture, transcutaneous electrical acupoint stimulation, cerebral ischemia/reperfusion injury, and cerebral protection", we retrieved articles from the PubMed database published between January 1991 and June 1994. Meanwhile, we searched the China National Knowledge Infrastructure with the same terms. Altogether, 114 articles and their results were analyzed. Inclusive criteria: studies that were closely related to the protective effects of acupuncture on brain ischemia/reperfusion injury, or studies, whose contents were in the same study field and were published recently, or in the authorized journals. Exclusive criteria: repetitive studies. LITERATURE EVALUATION: Thirty articles that related to the protective effects of acupuncture on brain ischemia/reperfusion injury were included. Among them, 7 were clinical studies, and the remaining 23 articles were animal experimental studies. DATA SYNTHESIS: ① Animal experimental studies have demonstrated that acupuncture improves brain blood perfusion and brain electrical activity, influences pathomorphological and ultramicrostructural changes in ischemic brain tissue, is beneficial in maintaining the stability of intracellular and extracellular ions, resists free radical injury and lipid peroxidation, and influences cytokine, neurotransmitter, brain cell signal transduction, and apoptosis-regulating genes. ② Clinical studies have demonstrated that acupuncture not only promotes nutritional supply to local brain tissue in patients with cerebral

  14. IMPACT OF SEVOFLURANE AND ACETYLCYSTEINE ON ISCHEMIA-REPERFUSION INJURY OF THE LIVER FROM BRAIN-DEAD DONOR

    Directory of Open Access Journals (Sweden)

    A. E. Shcherba

    2013-01-01

    Full Text Available Aim. The purpose of our work was to estimate the impact of preconditioning with acetylcysteine and sevoflurane on ischemia-reperfusion injury of cadaveric donor liver with marginal features. Methods and results. In this prospective randomized controlled trial we recruited 21 heart beating donors with brain death. We assigned 11 donors to the study group, and 10 donors to the control group. Morphological characteristics of ischemia- reperfusion injury in both groups were analyzed. Conclusion. Use of pharmacological preconditioning with acetylcysteine and sevoflurane resulted in necrosis and hepatocyte apoptosis reduction as compared to the control group, thereby had a protective effect against ischemia-reperfusion injury. 

  15. Impact of ischemia-reperfusion on extracellular matrix processing and structure of the basement membrane of the heart.

    Directory of Open Access Journals (Sweden)

    Alexander Lauten

    Full Text Available PURPOSE: Acute ischemic injury is a strong inductor of cardiac remodelling, resulting in structural changes of the extracellular matrix (ECM and basement membrane (BM. In a large animal model of ischemia-reperfusion (I/R we investigated the post-ischemic liberation of the collagen-IV-fragments Tumstatin (TUM; 28 kDa-fragment of collagen-IV-alpha-3, Arresten (ARR; 26 kDa-fragment of collagen-IV-alpha-1 and Endorepellin (LG3, 85 kDa-fragment of perlecan which are biologically active in angiogenesis and vascularization in the post-ischemic myocardium. METHODS AND RESULTS: In this blinded study, 30 pigs were randomized to 60 min of global I/R at either 4°C or 32°C or served as control. Three transmyocardial tissue samples were collected prior to ischemia and within 30 min and 150 min of reperfusion. Tissue content of TUM, ARR and LG3 was analyzed by western blotting and immunostaining. Within 150 min of mild hypothermic I/R a significantly increased tissue content of ARR (0.17±0.14 vs. 0.56±0.56; p = 0.001 and LG3 (1.13±0.34 vs. 2.51±1.71, p11fold elevation of creatine kinase (2075±2595 U/l vs. 23248±6551 U/l; p<0.001 in the coronary sinus plasma samples. Immunostaining demonstrated no changes for ARR and LG3 presentation irrespective of temperature. In contrast, TUM significantly decreased in the BM surrounding cardiomyocytes and capillaries after mild and deep hypothermic I/R, thus representing structural al