首页|期刊导航|中华医学杂志（英文版）|Attenuation of myocardial apoptosis by alpha-lipoic acid through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy
中华医学杂志（英文版）Issue(21)：2580-2586,7.DOI:10.3760/cma.j.issn.0366-6999.2009.21.010
Attenuation of myocardial apoptosis by alpha-lipoic acid through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy
Attenuation of myocardial apoptosis by alpha-lipoic acid through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy
摘要
Abstract
Background Cardiac failure is a leading cause of the mortality of diabetic patients.In part this is due to a specific cardiomyopathy,referred to as diabetic cardiomyopathy.Oxidative stress is widely considered to be one of the major factors underlying the pathogenesis of the disease.This study aimed to test whether the antioxidant α-lipoic acid(α-LA)could attenuate mitochondrion-dependent myocardial apoptosis through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy.Methods A rat model of diabetes was induced by a single tail intravenous injection of streptozotocin(STZ)45 mg/kg.Experimental animals were randomly assigned to 3 groups:normal control(NC),diabetes(DM)and DM treated with α-LA (α-LA).The latter group was administered with α-LA(100 mg/kg ip per day),the remainder received the same volume vehicle.At weeks 4,8,and 12 after the onset of diabetes,cardiac apoptosis was examined by TUNEL assay.Cardiomyopathy was evaluated by assessment of cardiac structure and function.Oxidative damage was evaluated by the content of malondialdehyde(MDA),reduced glutathione(GSH)and the activity of manganese superoxide diamutase (Mn-SOD)in the myocardial mitochondria.Expression of caspase-9 and caspase-3 proteins was determined by immunohistochemistry and mitochondrial cytochrome c release was detected by Western blottingResults At 4,8,and 12 weeks after the onset of diabetes,significant reductions in TUNEL-positive cells,caspase-9,-3 expression,and mitochondrial cytochrome c release were observed in the α-LA group compared to the DM group.In the DM group,the content of MDA in the myocardial mitochondria was significantly increased,and there was a decrease in both the mitochondrial GSH content and the activities of Mn-SOD.They were significantly improved by α-LA treatment.HE staining displayed structural abnormalities in diabetic hearts,while α-LA reversed this structural derangement.The index of cardiac function(±dp/dtmax)in the diabetes group was aggravated progressively from 4 weeks to 12 weeks,but α-LA delayed deterioration of cardiac function(P＜0.05).Conclusions Our findings indicate that the antioxidant α-LA can effectively attenuate mitochondria-dependent cardiac apoptosis and exert a protective role against the development of diabetic cardiomyopathy.The ability of α-LA to suppress mitochondrial oxidative damage is concomitant with an enhancement of Mn-SOD activity and an increase in the GSH content of myocardial mitochondria.关键词
alpha-lipoic acid/myocardial apoptosis/mitochondrial oxidative stress/diabetic cardiomyopathyKey words
alpha-lipoic acid/myocardial apoptosis/mitochondrial oxidative stress/diabetic cardiomyopathy分类
医药卫生引用本文复制引用
LI Chun-jun,ZHANG Qiu-mei,LI Ming-zhen,ZHANG Jing-yun,YU Pei,YU De-min..Attenuation of myocardial apoptosis by alpha-lipoic acid through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy[J].中华医学杂志（英文版）,2009,(21):2580-2586,7.基金项目
This work was supported in part by Metabolic Disease Hospital Foundation and University Scholar of the Tianjin Medical University(No.2006ky43). （No.2006ky43）
