Protective effects of gliclazide on myocardium of diabetic rats and its mechanism

Abstract

Objective: To investigate the protective effects of gliclazide on myocardium of diabetic rats and its possible mechanisms. Methods: Sixty healthy SD rats were randomly divided into two groups: normal group (NC, n=10) and model group (n=50). Rats in model group were fed with high glucose and high fat diet for 4 weeks and then intraperitoneally injected with STZ (45 mg/kg) to establish a diabetic model and randomly selected FBG ≥ 16.7 mmol / L as a successful diabetes model. Thirty-eight diabetic rats were randomly divided into model group (MC, n=9), gliclazide group (Glic, 80 mg/kg, n=10), glibenclamide group (Glib, 2.5 mg/kg, n=10) and fasudil group (Fas, 10 mg/kg, n=9). NC group and MC group were given equal volume distilled water by gavage, Glic group and Glib group were treated with gliclazide or glibenclamide by gavage, and the Fas group was treated with fasudil by intraperitoneal injection. Rats in each group were given once a day and recorded body mass and fasting blood glucose (FBG) weekly for 8 weeks. At the end of the experiment, the heart weight was measured, and the heart weight index (HWI) was calculated; the contents of glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), the level of serum malondialdehyde MDA) and the activity of superoxide dismutase (SOD) were measured; the pathological changes of myocardial tissue were observed by HE and Masson staining. The expressions of RhoA, ROCK1, eNOS, Bcl-2 and Bax protein were detected by Western blot. Results: Compared with NC group, in MC group, the levels of FBG, HWI, HbA1c, TC, TG, LDL-C, MDA, myocardial collagen deposition and cardiomyocyte apoptosis rate and RhoA, ROCK1, Bax protein in myocardial tissue were increased significantly, while the SOD activity, the levels of HDL-C, eNOS, Bcl-2 and body weight were decreased significantly (P＜0.01). Compared with MC group, Glic treatment decreased the levels of FBG, HWI, HbA1c, LDL-C, TG, TC and MDA, increased the levels of SOD activity and HDL-C (P＜0.01 or P＜0.05); decreased myocardial collagen deposition, inhibited cardiomyocyte apoptosis (P ＜ 0.01); decreased the expression levels of RhoA, ROCK1 and Bax protein; increased the levels of eNOS and Bcl-2 protein (P＜0.01 or P＜0.05). Compared with Glic group, in Glib group, the levels of blood lipids, BM, FBG, HWI, MDA, myocardial fibrosis and cardiomyocyte apoptosis rate were increased, the levels of SOD and Bcl-2 were decreased, and the expressions of RhoA, ROCK1 and Bax in myocardial tissue were upregulated (P＜0.01 or P＜0.05). Conclusion: Gliclazide significantly alleviates myocardial injury and reduces myocardial apoptosis in diabetic rats, and its mechanism may be related to lowering blood glucose, improving oxidative stress and regulating RhoA / ROCK1 / eNOS signaling pathway.