Abstract: ObjectiveTo explore the effect of alpha lipoic acid(A-LA) on myocardial apoptosis mediated by endoplasmic reticulum stress(ERS) in diabetic rats.MethodsFifty healthy male Sprague-Dawley rats with 250 to 300 g of body weight were selected.The rat diabetes model was established with streptozotocin(STZ) and the diabetic rats were randomly divided into 5 groups:normal group,diabetic group,low,moderate,and high dose A-LA groups at the doses of 15,30,and 60 mg/kg/d by gastric gavage for 12 weeks.The normal group and diabetic group were treated with normal saline daily.Blood glucose,cardiac function,cardiac mass index,and left ventricular mass index of the rats were determined.Apoptosis was detected by TdT-mediated dUTP nick end labeling(TUNEL).The expressions of glucose-regulated protein 78(GRP78) and C/EBP homologous protein(CHOP) were detected with western blotting.ResultsCompared to those of the control group,blood sugar(26.15?4.24 mmol/L)and left ventricular end-diastolic pressure(LVEDP)(9.57?1.16 mmHg)of the diabetic group were significantly increased (P<0.01),but left ventricular systolic pressure(LVSP62.45?4.10 mmHg),眒aximun rate-of-rise left ventricular pressure (LVdp/dtmax4502.32?238.92 mmHg/s) were significantly reduced(P<0.01).The indexes of ventricular mass and left vertricular mass were significantly higher in diabetic rats and the indexes of A-LA treatment groups were improved compared to the diabetic group.Compared to the control group,the apoptosis of diabetic rats(11.28?0.33%) increased significantly(P<0.05) and the expressions of GRP78 and CHOP protein were increased.The apoptosis of A-LA treatment groups was significantly reduced and GRP78 and CHOP protein expressions were decreased(P<0.01).ConclusionA-LA has protective effect on cardiomyopathy in diabetic rats and its mechanism may be associated with ERS.