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

DU Hui-xue; JIANG Hai-yu; HU Ying-ying; JIA Dan; HAI Xin

Abstract：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 mmol· L-1),high glucose group (40 mmol· 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-methyladenine (3-MA) group (100 μmol·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 mitochondrial transmembrane potential were observed.The expressions of ATG7,Beclin1,P62,LC3,SOD and SIRT1 were detected by Western Blot.Results:In type 2 diabetic myocardium,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.