白藜芦醇对大鼠肝缺血再灌注损伤的保护作用及其与Sirt1-p53通路的关系  

Protective effect of resveratrol against hepatic ischemia reperfusion injury in rats and its relationship with Sirt1-p53 signaling pathway

作　　者：苟毅[1] 余天雾[1] 黄中荣[1] 张雷达[2] 

机构地区：[1]重庆医科大学附属永川医院肝胆外科,重庆永川402160 [2]第三军医大学西南医院全军肝胆外科研究所,重庆400038

出　　处：《第三军医大学学报》2017年第13期1366-1370,共5页Journal of Third Military Medical University

基　　金：重庆医科大学附属永川医院院内项目(YJQN201432)~~

摘　　要：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 effect of resveratrol （RES） on hepatic ischemia reperfusion injury （HIRI） in rats and explore the underlying molecular mechanism. Methods Twenty male SD rats （ aged 6 weeks, weighting 200 ± 20 g） were randomly divided into 4 groups （ n = 5 ） ： sham operation group, HIRI group, RES pretreatment group, and RES pretreatment ＋ inhibitor group. The rat model of 70% hot liver ischemia-reperfusion was established through ischemia for 1 h followed by reperfusion for 6 h. RES and Sirtl inhibitors, EX527 were gave in the rats from the pretreatment group 1 h before the model infliction. Serum ALT activity and SOD activity in liver tissue were detected. The pathological changes of liver tissues were observed by HE staining. The apoptosis of hepatocytes were detected by TUNEL. The expression levels of Sirtl, acetylation p53 and Bax were analyzed by real-time fluorescent quantitative PCR and Western blotting. Results RES significantly reduced the increased ALT activity caused by HIRI （ P 〈 0.01 ） and enhanced the activity of SOD （P 〈0.01 ）, alleviated the pathological changes of the liver tissues induced by HIRI （P 〈 0.01 ）, and decreased the apoptosis of liver cells （P 〈 0.01 ）. Moreover, RES obviously increased of the transcriptional levels of Sirtl and Bax （ P 〈 0.01 ）, improved their protein levels （ P 〈 0.01 ）, butdown-regulated the expression of acetylation p53 at protein level （ P 〈 0.01 ） the liver injury induced by ischemia reperfusion, which may be partially signaling pathway. Conclusion RES attenuates through activation of Sirtl-p53

关 键 词：白藜芦醇 肝缺血再灌注损伤 sirt1-p53通路 

分 类 号：R285.5[医药卫生—中药学] R364.12[医药卫生—中医学]