Effect Of α-lipoic Acid On Myocardial Apoptosis Of Diabetic Rat Mediated By Endoplasmic Reticulum Stress

ObjectiveThrough the observation of alpha lipoic acid in diabetic rat myocardial cell protection. To investigate the expressions of GRP78, CHOP and Caspase-12the molecules related ERS in the diabetic rats.MethodsSixty healthy male Sprague-Dawley rats of250to300g of body weight were selected. The fifty rats were establested diabetesmellitus rat model by tail vein injection of streptozotocin(STZ) of30mg/kg, and ten rats were randomly selected to the normal control group. the diabetic rats randomly divided into four groups:diabetic group, A-LA low, medium and high dose groups at the doses of15,30and60mg/kg/d by gastric gavage for12weeks. The normal group and diabetic group were treated with normal saline and free diet daily. Blood glucose, left ventricular systolic pressure, left ventricular end-diastolic pressure±dp/dtmax, cardiac mass index and left ventricular mass index of the rats were tested after12weeks; Apoptosis was detected by TdT-mediated dUTP nick end labeling(TUNEL); The expression of glucose-regulated protein78(GRP78), C/EBP homologous protein(CHOP) and Caspse-12were detected by Western blotting of the rats. Protein expression of GRP78on heart by im m unoh istochem istry.ResultsCompared with the normal control group, fasting blood glucose cardiac insufficiency, cardiac insufficiency, HMI and LVMI of the diabetic rats were significantly up-regulated (P<0.01); The protein expression of GRP78, CHOP and Caspase-12were increased significantly, apoptosis increased significantly(P<0.01). But the three doses of a-lipoic acid relieved these damages. Fasting blood glucose of a-lipoic acid therapy groups was significantly decreased(P<0.01); Myocardial hypertrophy has improved.+dp/dtmax and-dp/dtmax were elevated. Heart function was better than befor. HMI and LVMI were improved. compared with diabetic group,the protein expression of GRP78, CHOP and Caspase-12were significantly decreased and the a-lipoic acid II group and a-lipoic acidⅢ group were the best(P<0.01). a-lipoic acid treatment group of apoptosis was significantly reduced(P<0.01).Conclusion1. a-lipoic acid has a protective effect on cardiac muscle in diabetic rats, it may reduce blood sugar, improve heart function and myocardial pathological structure.2. Strough the a-lipoic acid treat, the diabstic rats apoptosis decrease significantly and it should be related with decreased GRP78, CHOP and Caspase-12expression and block the opoptosis pathway caused by the ERS.