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目的探讨白藜芦醇(resveratrol,RES)对大鼠肝脏缺血再灌注损伤(hepatic ischemia reperfusion injury,HIRI)的保护作用及其具体分子机制。方法雄性6周龄SD大鼠20只[体质量(200±20)g]随机数字法分为4组(n=5):假手术组、缺血再灌注组、RES预处理组、RES预处理+抑制剂组。建立大鼠肝脏70%热缺血再灌注模型(缺血1 h,再灌注6 h),并提前1 h给予RES及Sirt1抑制剂(EX527)。建模后检测血清标本中ALT活力及肝组织SOD活性,HE染色观察肝组织病理损伤,TUNEL法检测肝细胞凋亡,实时荧光定量PCR和Western blot检测肝组织Sirt1、乙酰化p53、Bax表达水平。结果 RES能够显著降低由HIRI引起的ALT活力升高(P<0.01)并增加SOD活性(P<0.01),显著缓解由HIRI引起的肝脏病理学改变(P<0.01)和减少肝细胞凋亡(P<0.01),显著提高Sirt1和Bax mRNA表达水平(P<0.01,P<0.01),提高Sirt1和Bax蛋白表达水平(P<0.01,P<0.01)并降低乙酰化p53蛋白表达水平(P<0.01)。结论 RES能减轻缺血再灌注诱导的肝脏损伤,该保护作用部分是通过激动Sirt1-p53通路实现。
Objective To investigate the protective effect of resveratrol (RES) on hepatic ischemia reperfusion injury (HIRI) in rats and its molecular mechanism. METHODS: Twenty male Sprague-Dawley (SD) rats of 6 weeks old (body mass (200 ± 20) g] were randomly divided into 4 groups (sham operation group, ischemia reperfusion group, RES preconditioning group, Treatment + inhibitor group. To establish a model of 70% hot ischemia-reperfusion in rat liver (ischemia 1 h, reperfusion 6 h), and RES and Sirt1 inhibitor (EX527) were given 1 h earlier. The activity of ALT and the activity of SOD in liver tissue were detected after modeling. The pathological changes of liver tissue were observed by HE staining. The apoptosis of hepatocytes was detected by TUNEL method. The expression of Sirt1, acetylated p53 and Bax in liver tissues were detected by real-time fluorescence quantitative PCR and Western blot . Results RES significantly reduced the activity of ALT induced by HIRI (P <0.01) and increased the activity of SOD (P <0.01), and significantly alleviated the hepatic pathological changes induced by HIRI (P <0.01) and decreased the apoptosis of hepatocytes (P <0.01, P <0.01), significantly increased Sirt1 and Bax mRNA expression (P <0.01, P <0.01), increased the expression of Sirt1 and Bax protein and decreased the expression of acetylated p53 protein 0.01). Conclusion RES can relieve liver injury induced by ischemia-reperfusion, which is partly through the activation of Sirt1-p53 pathway.