Astragaloside Iv Improves Myocardial Damage In Diabetic Rats Induced By STZ Via Inhibiting AMPK/mTOR Pathway

ObjectiveThe purpose is to investigate the protective effect of ASIV on myocardial damage in diabetic rats induced by STZ,and its effect on AMPK/mTOR pathway,oxidative stress and ventricular remodeling.The main aim of the present study to explore the effects of ASIV on reducing oxidative stress and improving myocardial hypertrophy by AMPK/mTOR pathway,and further improving myocardial damage in STZ-induced diabetic rats.Methods40 six-week-old male SD rats were randomly divided into five groups with 8rats in each group:normal control group,diabetic model group,ASIV low-dose group(20mg·kg^-1),ASIV middle-dose group(40mg·kg^-1),ASIV high-dose group(80 mg·kg^-1).The rats of model group and different doses of ASIV group were injected with STZ(50 mg·kg^-1,intraperitoneal injection)at a high dose for five days,and the rats of random blood glucose>15 mmol·L^-1was regarded as successful model.After successful modeling,given different doses of ASIV for12 weeks.After 12 weeks,the glucose concentration in rat serum was measured by glucose kit,and the cardiac hemodynamic parameters were measured with a physiological recorder.The body weight,total heart and left ventricular weight were measured,and calculate the heart weight index（HWI）and left ventricle weight index（LVWI）.The activities of AST,LDH,Mito-SOD and Mito-CAT were detected by kit method.The morphology and arrangement of cardiomyocytes were observed by the hematoxylin and eosin（HE）staining.Protein extracted from left ventricular tissue was used to detect the expression of AMPK,p-AMPK,m TOR,p-mTOR,ANP,BNP and Mito-NOX4 by Western Blot.The expression of ANP and BNP m RNA was detected by RT-PCR.ResultsIn diabetic model group,blood glucose was increased significantly,LVEDP was increased,LVSP and±dp/dtmax was decreased significantly,AST and LDH activity increased significantly,HWI and LVWI was rised significantly.HE staining showed that myocardial cells were disordered and cell surface area was significantly increased.The oxidative index of the activity of Mito-SOD and Mito-CAT were significantly decreased,the protein expression of Mito-NOX4was increase,p-AMPK/AMPK was declined,p-mTOR/mTOR was increased,the protein and mRNA expression of ANP and BNP were significantly increased.The expression of p-mTOR oberserved byimmunohistochemistry was increased.Compared to the model group,in the different doses of ASIV groups,blood glucose was decreased significantly,LVEDP was decreased,while LVSP and±dp/dtmax was increased significantly,the activity of AST and LDH decreased,HWI and LVWI was decreased.HE staining showed that myocardial cells arranged in neat rows,the cell surface area decreased,increased the activity of Mito-SOD and Mito-CAT,decreased the expression of Mito-NOX4,increased the expression of p-AMPK/AMPK,decreased the expression of p-mTOR/mTOR,and the protein and mRNA expression of ANP and BNP was significantly reduced,immunohistochemical observation p-m TOR expression decreased.Conclusions1.AMPK/m TOR pathway activation,oxidative stress and ventricular remodeling damage are present in STZ-induced diabetic rats,thereby aggravating myocardial damage.2.ASIV may reduce oxidative stress and delay myocardial hypertrophy by inhibiting AMPK/mTOR pathway,thereby improving myocardial damage.