白藜芦醇通过上调SIRT1促进自噬抑制2型糖尿病心肌病  

Resveratrol attenuates type 2 diabetes-induced cardiomyopathy through promoting autophagy by up-regulating SIRT1

作　　者：杜慧雪[1] 姜海宇 胡莹莹[1] 贾丹[3] 海鑫 

机构地区：[1]哈尔滨医科大学附属第一医院药学部,哈尔滨150080 [2]哈尔滨医科大学附属第一医院超声科,哈尔滨150080 [3]哈尔滨医科大学附属肿瘤医院药学部,哈尔滨150080

出　　处：《中国新药杂志》2017年第24期2970-2977,共8页Chinese Journal of New Drugs

摘　　要：目的:探讨白藜芦醇(RSV)对2型糖尿病心肌中自噬功能的影响并对其分子机制进行探讨。方法:8周龄自发性2型糖尿病db/db小鼠与同源不发病db/m小鼠,随机分为正常对照组(db/m组)、模型组(db/db组)、白藜芦醇给药组(db/db+RSV组),db/db+RSV组小鼠灌胃白藜芦醇400 mg·kg-1·d-112周。H9c2细胞分为正常对照组(5.5 mmol·L^(-1)葡萄糖)、高糖高脂组(40 mmol·L^(-1)葡萄糖+200 mmol·L^(-1)palmitate)以及给予白藜芦醇治疗组(resveratrol,RSV,100μmol·L^(-1))、给予线粒体抗氧化剂治疗组(MitoTempo,2μmol·L^(-1))、给予自噬抑制剂组(3-methyladenine,3-MA,100μmol·L^(-1))处理H9c2细胞48 h。高糖高脂培养H9c2细胞模拟高血糖和高血脂的2型糖尿病模型。H9c2细胞小片段干扰RNA(siRNA)干涉SIRT1基因后,观察H9c2细胞中ROS含量、自噬体、线粒体膜电位,Western Blot检测自噬标志蛋白ATG7,Beclin1,P62,LC3,SOD和SIRT1蛋白的表达水平。结果:2型糖尿病心肌中,SIRT1和自噬水平下降,线粒体ROS产生增多,膜电位下降。给予白藜芦醇和抗氧化剂处理后SIRT1和自噬水平均增加,线粒体功能提高。结论:白藜芦醇可能通过SIRT1促进心肌细胞自噬,从而提高心肌线粒体抗氧化能力。Objective：To observe the effect of resveratrol on autophagy in type 2 diabetes cardiomyopathy and its molecular mechanism. Methods： Eight week-old db/db mice and homology db/m mice with spontaneously type 2 diabetes mellitus were divided into normal group （db/m group）, model group （db/db group） and resveratrol group （db/db ＋ RSV） and fed for 12 weeks. RSV group were treated with resveratrol of 400 mg·kg^-1·d^-1. H9c2 cells were randomly divided into the following groups ： control group （ low glucose, LG, 5.5 mol· L^-1 ） , high glucose group （40 mol· L^-1 glucose ＋ 200 μmol·L^-1 palmitate） , Resveratrol group （ RSV, 100 μmol·L^-1 ） , Mito-Tempo group （2 μmol·L^-1, an inhibitor of mitochondrial reactive oxygen species） , 3-metbyladenine （3-MA） group （100μmol·L^-1, an inhibitor of autophagy）. Drugs were added directly into culture medium and treated for 48 h. H9c2 cells were treated with high glucose and palmitate to mimic type 2 diabetes with hyperglycemia and hyperlipidemia. With treatment of SIRT1 gene interfered with siRNA, the ROS, autophagy and mitoehondrial transmembrane potential were observed. The expressions of ATGT, Beclinl, P62, LC3, SOD and SIRT1 were detected by Western Blot. Results： In type 2 diabetic myoeardium, the expression level of SIRT1 and the level of autophagy were decreased, ROS production was increased and mitochondrial transmembrane potential was decreased.The treatment of resveratrol increased the expression level of SIRT1 and the level of autophagy, and improved the mitochondrial function. Conclusion： Resveratrol can protect cardiocytes against oxidative stress by promoting autophagy through increasing the expression of SIRT1.

关 键 词：白藜芦醇 SIRT1 自噬 抗氧化 

分 类 号：R965[医药卫生—药理学]