Zhang Rui-Ying, Yu Ping, Wang Fei, Shen Jing-Xia, Wang Yu-Mie
Department of Cardiovascular, First Hospital, Harbin Medical University, Harbin150001, China.
Zhonghua Yi Xue Za Zhi. 2009 May 12;89(18):1240-5.
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.
研究糖尿病大鼠心肌梗死后心脏结构和功能的变化，探讨葡萄糖转运蛋白4（GLUT4）的表达及曲美他嗪对心室重构的影响。
采用高糖高脂高胆固醇饲料喂养6周后腹腔注射链脲佐菌素制备2型糖尿病大鼠模型，然后结扎冠状动脉造成心肌梗死。术后24小时将存活大鼠随机分为三组：安慰剂组；曲美他嗪组；糖尿病假手术组。另将正常饮食喂养的大鼠分为非糖尿病心肌梗死组和非糖尿病假手术组。曲美他嗪组大鼠用蒸馏水配制的曲美他嗪溶液灌胃（30mg·kg⁻¹·d⁻¹），其余组灌胃等体积蒸馏水。6周后行超声心动图和血流动力学检查，称量心室重量，检测心肌梗死面积及非梗死区心肌胶原容积分数（CVF）。采用荧光定量RT-PCR检测梗死周边区心肌GLUT4 mRNA表达，Western blot检测GLUT4蛋白表达。
糖尿病合并心肌梗死后6周，与非糖尿病假手术组、糖尿病假手术组和非糖尿病心肌梗死组比较，糖尿病合并心肌梗死组左室舒张末期内径（LVDd）显著增大；左室收缩和舒张功能显著降低，心室重量指数（VWI）和CVF显著增加；与安慰剂组比较，曲美他嗪组左室舒张功能显著改善（4.7±1.7 vs 6.8±1.6，P<0.05）；CVF显著降低（3.9±0.2)% vs (6.3±0.4)%，（P<0.05），但LVDd、VWI和收缩功能无显著变化。糖尿病假手术组和糖尿病合并心肌梗死组GLUT4 mRNA和蛋白表达较非糖尿病假手术组显著降低（P<0.01）。与安慰剂组比较，曲美他嗪组GLUT4蛋白表达中度增加（P<0.05）。
曲美他嗪可改善糖尿病合并心肌梗死后左室舒张功能。2型糖尿病合并心肌梗死后GLUT4 mRNA和蛋白表达降低。曲美他嗪可提高糖尿病合并心肌梗死后GLUT4 mRNA和蛋白表达，抑制心肌纤维化。
