Effects of Trimetazidine upon ventricular remodeling and GLUT4 in diabetic rats after myocardial infarction

Abstract

The aim of study is to investigate the changes of structure and function of heart in diabetic rat after myocardial infarction, and to study the expression of the GLUT4 and the effects of trimetazidine on the ventricular remodeling. Type 2 diabetes rat was made by feeding with a diet enriched with sucrose, fat and cholesterol for six weeks and then injecting streptozocin intraperitoneally, then the myocardial infarction by ligating coronary artery. The living rats were randomly divided into three groups twenty-four hours after operation: placebo; trimetazidine and sham operated with diabetes. And other rats which was fed with normal diet were divided into myocardial infarction group without diabetes and sham operated group without diabete. The treat group was intragastric administrated with trimetazidine which was solved in distilled water (30 mgxkg(-1) 1xd(-1)), and others were poured with parts aequalis distilled water. After six weeks, echocardiographic and hemodynamic studies were performed, ventricular were weighed, myocardial infarct size and myocardial collagen volume fraction (CVF) of non-infarction area were detected also. GLUT4 mRNA in the myocardium away from infarction region were measured with fluorescent quantitation RT-PCR and GLUT4 protein were measured with Western blot. Six weeks after diabetes complicating with myocardial infarction, comparing with sham operated group without diabete, diabetes sham operated group and myocardial infarction group without diabete, LVDd of diabetes complicating with myocardial infarction group was increased significantly; the systolic and diastolic function with left ventricular were decreased significantly, VWI and CVF were increased significantly; comparing with placebo group, diastolic function of left ventricular in trimetazidine group was improved significantly (4.7 +/- 1.7 vs 6.8 +/- 1.6, P < 0.05); CVF (3.9 +/- 0.2)% vs (6.3 +/- 0.4)%, (P < 0.05) was decreased significantly, but LVDd, VWI and the systolic function was not chang significantly. The expression of GLUT4 mRNA and protein in sham operated with diabetes and diabetic with myocardial infarction descended significantly compared with sham operated group without diabete (P < 0.01). And in trimetazidine group, GLUT4 protein moderately increased (P < 0.05) compared with placebo group. Trimetazidine could improve the diastolic function of left ventricular. The expression of GLUT4 mRNA and protein in type 2 diabetes complicating with myocardial infarction decreased. Trimetazidine could improve the expression of GLUT4 mRNA and protein in diabetes complicating with myocardial infarction and inhibited myocardial fibrosis.