雷米普利对糖尿病心肌梗死大鼠葡萄糖转运体4的影响

目的 观察2型糖尿病合并心肌梗死大鼠室重构及葡萄糖转运体(GLUT4)表达及雷米普利对其影响.方法 46只雄性Wistar大鼠由哈尔滨医科大学第一临床医学院实验动物中心提供.高脂喂养加低剂量链脲佐菌素(STZ,30mg/kg)腹腔注射,血糖值≥16.7 mmol/L为2型糖尿病模型,结扎冠状动脉左前降支制备心肌梗死模型;糖尿病合并心肌梗死大鼠随机(随机数字法)分为安慰剂组(n,=9),雷米普利组(n=10),糖尿病假手术组(n=10);非糖尿病大鼠随机分为心肌梗死组(n=9)及非糖尿病假手术组(n=8).术后6周查心脏超声、测定心室重量指数、心肌梗死面积及左室非梗死区心肌胶原容积分数.取大鼠非梗死区心肌,采用实时定量RT-PCR技术测定GLUT4 mRNA.Western blot法测定GLUT4蛋白含量.用SPSS 13.0统计软件进行统计学分析;组间比较用方差分析,P<0.05为差异具有统计学意义.结果 与糖尿病假手术组和非糖尿病心肌梗死组相比,安慰剂组EF值显著降低(32±3)%vs.(65±4)%,P<0.01;(32±3)%vs.(38±4)%,P<0.05];E/A比值(P<0.01)、左室非梗死区胶原容积分数(P<0.05)及心室重量指数(P<0.05)升高.与安慰剂组相比,雷米普利组盯值改善明显(45±3)%vs.(32±3)%,P<0.01],且E/A比值显著降低(P<0.01),左室非梗死区胶原容积分数下降、心室重量指数减少(3.1±0.2) vs.(4.2±0.4),P<0.01].安慰剂组GLUT4 mRNA及蛋白表达较非糖尿病心肌梗死组低,与糖尿病假手术组相比差异无统计学意义.与安慰剂组相比,雷米普利组GLUT4 rnRNA及蛋白表达升高.结论 雷米普利可防治心室重构并改善心脏收缩及舒张功能;2型糖尿病合并心肌梗死大鼠心肌GLUT4 mRNA和蛋白的表达下降,雷米普利可以改善糖尿病合并心肌梗死大鼠心肌GLUT4 mRNA和蛋白的表达.

Effects of Ramipril on the ventricular remodeling and GLUT4 in diabetic rats complicated with myocardial infarction

Objective To investigate ventricular remodeling and glucose transporter 4(GLUT4) expression in rat with type 2 diabetes mellitus(DM) complicated with myocardial infarction (MI), as well as the effects of ramipril on ventricular remodeling and CLUT4 expression. Method Diabetic animal model (DM) was produced by cholesterol-diet and intraperitoneal injedtion of streptozotocin (STZ,30 mg/kg). The successful model was identified based on the blood gulcose value > 6.7 mmol/L. Left anterior descending coronary artery was ligated to produce the model of MI. 46 wistar rats were randomly(random number) divided into 5 groups: DM + MI + placebo group(placebo group, n = 9), DM + MI + ramipril group(ramipril group, n = 10), DM + sham-operation group (DM group, n = 10),non-DM group + MI (MI group, n = 9), and non-DM + sham-operation group (n = 8). After six weeks, echocardiographic studies was performed ; Left ventricular mass index (LVMI), myocardial infarct size and myocardial collagen volume fraction(CVF) of non-infarction area were also detected. GLUT4 mRNA in the myocardium away from infarction region was measured with real-time fluorescent quantitative RT-PCR and the expression of GLUT4 protein was measured with western blot. Analysis of variance was used to compare the groups. P -values< 0.05 were considered to indicate statistically significant differences. Results Compared with Ml group and DM group,EF(32 ±3)% vs. (65 ±4)%, P <0.01 and (32 ±3)% vs. (38 ±4)%, P <0.05 respectively] significantly decreased,while E/A ratio (P < 0.01), LVMI (P < 0.05) and CVF (P < 0.05) obviously increased in placebo group. The expression of GLUT4 mRNA and protein were similar between placebo group and DM group, however, much lower than those in MI group(P<0.01).In rampiril group, E/A ratio (P < 0.01), LVMI(3.1±0.2 vs.4.2±0.4, P <0.01) and CVF(P < 0.05) significantly decreased compared with placebo group, while EF(45±3)% vs.(32±3)%, P <0.01] and the expression of GLUT4 mRNA and protein (P < 0.05) increased. Conclusions Rampiril could improve left ventricular hypertrophy and systolic/di-astolic dysfunction, increase the expression of GLUT4 mRNA and protein in diabetic rats complicated with MI.