Abstract: ObjectiveTo explore protective effect of alpha-lipotic acid(ALA)on diabetes cardiomyopathy and its mechanism.MethodsSD rats were randomly divided into normal control,diabetes model,low,moderate and high dose ALA treatment groups with a peritoneal injection of streptozotocin(STZ)of 60 mg/kg.The rats in ALA treatment groups were administrated by gavage with ALA at the dosages of 15,30,and 60 mg/kg a day for 12 weeks.The contents of blood sugar and serum fructosoamine were detected.Immunohistochemistry method and western blot method were used to determine matrix metalloproteinase-9(MMP-9),metalloproteinase-2(MMP-2),and tissue inhibitors of matrix metalloproteinase-1 metal protease organization inhibitory factor-1(TIMP-1)in myocardial tissue of the rats.Resultscompared with those of the control group(4.62±1.03,3.2±0.19),fasting blood glucose and serum fructosamine of the diabetic rats(25.45±3.24, 4.43±0.62)were significantly up-regulated(P<0.05).Cardiac function test showed that left ventricular end-diastolic pressure(LVEDP)increased and left ventricular systolic pressure(LVSP),±dp/dtmax declined significantly in diabetecs rats compared with those of control rats(P<0.05 for all)and the protein expressions of MMP-2(68.9±4.35),MMP-9 (87.38±11.10),TIMP-1(81.82±9.61),and MMP-9/TIMP-1(1.07±0.06)were also significantly up-regulated in the diabetic rats(P<0.05 for all).compared with the diabetic group,fasting blood glucose and serum fructosamine of the ALA treated rats were significantly decreased(P<0.05 for all)and LVEDP(5.60±0.98 mmHg)deccreased significantly (P<0.05)and LVSP(127.55±5.45 mmHg)elevated(P<0.05).The protein expression of MMP-2(62.26),MMP-9 (76.78),TIMP-1(72.87)and MMP-9/TIMP-1(1.03)of ALA treated rats were significantly decreased compared to those of the diabetic model rats(P<0.05 for all).ConclusionALA has protective effect on diabetic cardiomyopathy through regulating MMPs and TIMP-1.