厄贝沙坦对糖尿病鼠心肌组织葡萄糖转运蛋白4干预研究
Effect of Irbesartan on GLUT4 of Myocardial Tissue in Streptozotocin-induced Diabetic Rats
-
摘要: 目的探讨厄贝沙坦对糖尿病鼠心肌组织中葡萄糖转运蛋白4(GLUT4)的作用及其意义。方法8周龄体重为250~300g雄性Wistar大鼠27只,腹腔注射STZ(50mg/kg)制成糖尿病鼠模型,饲养11周;观察A组(正常对照组)、B组(糖尿病对照组)、C组(厄贝沙坦用药组:血糖稳定1周后厄贝沙坦50mg/kg.d灌胃)造模前、造模后48小时及造模后11周心肌组织GLUT4(免疫组化法测定)及血糖变化(普通生化法测定)。结果(1)GLUT4的变化:B组术后48hGLUT4无明显改变,但术后11周时GLUT4水平明显下降(208.89±10.96vs143.56±16.99)组化灰度值;P<0.01;C组术后48hGLUT4未见明显变化。(2)血糖的变化:A组,不同时间血糖无明显变化,B组,术后48h及术后11周,血糖升高(16.89±2.46,18.45±2.60vs3.80±1.09)mmol/L,P均小于0.01。C组,术后48h血糖升高,术后11周时血糖较48h有所下降但未达统计学意义(18.32±4.06vs15.84±2.60)mmol/L,P>0.05)。结论糖尿病时心肌组织GLUT4水平下降可能参与糖尿病心肌病的形成;厄贝沙坦具有上调糖尿病心肌组织GLUT4的作用,提示ARB在糖尿病患者中早期应用还能改善病人糖的摄取、代谢。Abstract: Background Abnormal glucose metabolism may be involved in the development of heart failure. Angiotensin receptor blockade has been reported to slow the progress of heart failure. Objective To investigate the significance of a decrease in GLUT4 levels in the diabetic heart and the preventive effect of Irbesartan. Methods Twenty-seven male Wistar rats (age: 8 weeks, weight: 250-300 g)were randomly divided into three groups: group A(normal rats), group B(the diabetic models), group C (the diabetic models with Irbesartan intervention). The diabetic models were obtained by STZ (50 mg/kg) IP. When the diabetic models were established, irbesartan (50 mg/kg·d ) was administered by gavage for 11 weeks. The alteration in GLUT4 in myocardial tissue (measured by immunohistochemistry) and plasma glucose were measured before 48 hours and 11 weeks after the models were made. Results (1) GLUT4 in myocardium was decreased apparently at 11 weeks after operation (208.89±10.96 vs143.56±16.99) grey value of immunochemistry(P<0.01) in group B suggesting GLUT4 was related with the development of diabetes. On the contrary , little changes in GLUT4 was found in group A and C. (2)Plasma glucose:plasma glucose was increased at 48 hours and 11 weeks after the operation in group B (16.89 ±2.46,18.45±2.60 vs. 3.80±1.09)mmol/L(P<0.01 both). Whereas, plasma glucose increased at 48 hours in group C but was likely recovered at 11 weeks after irbesatan treatment (18.32±4.06 vs 15.84±2.60)mmol/L(P>0.05). Conclusion The decrease of GLUT4 in diabetic myocardial tissue may be involved in the formation of diabetic cardiomjyopathy. Irbesartan up-regulated the expression of GLUT4 in diabetic myocardial tissue.