罗格列酮对2型糖尿病大鼠心肌脂联素及其受体1蛋白表达的影响  

Effect of rosiglitazone on protein expression of cardiac adiponectin and its receptor type 1 in rats with type 2 diabetes

作　　者：郭志新[1] 秦志宏[1] 魏萍[1] 郑彩虹[1] 徐国君[1] 赵慧琴[1] 

机构地区：[1]山西医科大学第二医院内分泌科,太原030001

出　　处：《解放军医学杂志》2009年第7期851-854,共4页Medical Journal of Chinese People's Liberation Army

基　　金：山西省留学基金项目(200744)

摘　　要：目的研究罗格列酮对2型糖尿病大鼠心肌脂联素以及心肌脂联素受体1(AdipoR1)表达的影响,探讨罗格列酮对糖尿病心肌病变的保护作用及机制。方法36只雄性Wistar大鼠,分为对照组(n=10)、糖尿病组(n=13)和罗格列酮组(n=13)。用高糖高脂饲料加小剂量链脲佐菌素建立2型糖尿病大鼠模型,成模后罗格列酮组给予3mg/(kg.d)罗格列酮及生理盐水混悬液灌胃3个月,对照组、糖尿病组给予同体积生理盐水灌胃3个月。3个月后处死动物,取出心脏,测量大鼠心脏重量(HW)并计算心脏重量与体重之比(HW/BW)。应用Western blotting检测各组心肌AdipoR1、AMP激活蛋白激酶-α(AMPK-α)、磷酸化AMPK-α、葡萄糖转运子4(GLUT4)蛋白的表达情况,酶联免疫吸附法检测血浆和心肌脂联素水平。通过颈动脉插管检测等容舒张期左室内压力下降最大速率(-dp/dtmax)。结果与对照组比较,糖尿病组大鼠3个月时HW/BW升高(P<0.05),而血浆和心肌脂联素水平及心肌Adi-poR1蛋白表达、磷酸化AMPK-α水平、GLUT4蛋白表达降低(P<0.05)。与糖尿病组比较,罗格列酮组大鼠HW/BW降低(P<0.05),血浆和心肌脂联素水平及心肌AdipoR1表达、磷酸化AMPK-α水平、GLUT4表达均升高(P<0.05)。与对照组比较,糖尿病组、罗格列酮组心功能均降低(P<0.05),等容舒张期左室内压下降的最大速率(-dp/dtmax)≤5250mmHg/s(正常值低限)。与糖尿病组比较,罗格列酮组心功能得到明显改善。结论2型糖尿病大鼠心肌脂联素及其受体1的表达水平降低。罗格列酮可上调心肌脂联素及其受体1的表达水平,促进心肌葡萄糖氧化,从而改善2型糖尿病大鼠的心功能。Objective To investigate the effects of rosiglitazone on the expression of cardiac adiponectin and its receptor type 1 in type 2 diabetic rats, and explore the protective effect and its mechanisms of rosiglitazone on diabetic cardiomyopathy. Methods Thirty-six male Wistar rats were randomly divided into control group, diabetic group and rosiglitazone group. Type 2 diabetes rat model was reproduced by feeding a high-fat, high-sugar diet followed by an intraperitoneal injection of a low dose of streptozotocin （STZ）. Rats in rosiglitazone group were laraged with rosiglitazone 3mg/（kg · d）, while in control group and diabetic group received same amount of normal saline for 3 months. After 3 months, rats were sacrificed, the heart of each rat was weighed and HW/BW was calculated. Cardiac protein expression of adiponectin receptor 1 （AdipoRl）, AMP-activated protein kinase a （AMPK-α）, phosphorylation of AMP activated protein kinase α-subunits and glucose transporter 4 （GLUT4） were determined by Western blotting. Plasma and myocardial adiponectin levels were assayed by enzyme immunoassay. The maximum descent speed （-dp/dtmax） in the left ventricle isovolumetric relaxation period was measured by carotid artery intubation. Results After 3 months, HW/BW was elevated, while plasma and myocardial adiponectin levels, the protein expression of AdipoR1, phosphorylation of AMPK-α and GLUT4 were significantly decreased in diabetic group compared with that in control group （P〈0. 05）. Compared with that in diabetic group, HW/BW declined, while plasma and myocardial adiponectin levels, protein expression of AdipoR1, phosphorylation of AMPK-α and GLUT4 in rosiglitazone group had significantly increased （P〈0. 05）. The heart function in both diabetic and rosiglitazone group was significantly decreased compared with that in control group. -dp/dtmax in the left ventricle isovolumic relaxation period was 5250mmHg/s or less. The heart function was obviously improved in rosiglitazone group compared wi

关 键 词：罗格列酮 脂联素 糖尿病 2型 心肌疾病 

分 类 号：R587.1[医药卫生—内分泌]