替米沙坦对糖尿病大鼠心肌脂联素及其受体1表达的影响  

On the expression of cardiac adiponectin and its receptor 1 by telmisartan in diabetic rats

作　　者：郑彩虹[1] 郭志新[1] 秦志宏[1] 魏萍[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：《中华内分泌代谢杂志》2010年第4期311-316,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：基金项目：山西省留学基金项目（2007-44）;山西省留学回国人员科技活动择优资助项目

摘　　要：目的观察替米沙坦对糖尿病大鼠心肌脂联素及其受体1表达的影响，探讨替米沙坦对糖尿病大鼠心肌病变的保护作用及机制。方法30只雄性Wistar大鼠随机分为对照组，糖尿病组和糖尿病替米沙坦治疗组（替米沙坦组）。用高糖高脂饲料加小剂量链脲佐菌素建立糖尿病大鼠模型。成模后，替米沙坦组予以替米沙坦（5mg·kg^-1·d^-1）灌胃12周。实验结束时，测定心功能，用酶联免疫法检测血浆和心肌脂联素水平，用RT-PCR方法检测心肌脂联素受体1（AdipoRl）mRNA表达，用Western印迹法检测心肌脂联素受体1、磷酸化的磷酸腺苷激活的蛋白激酶-α（AMPK-α）、葡萄糖转运子4（GluT4）蛋白表达。结果与正常对照组比较，糖尿病组大鼠12周时出现心重／体重增加[（4．38±0．07对2．99±0．67）g/kg，P〈0．05]，心功能降低，血浆和心肌脂联素水平降低[（1．09±0．03对1．87±0．05）μg／ml，（0．12±0．02对0．21±0．02）μg／mg蛋白，均P〈0．05]，心肌脂联素受体1mRNA和蛋白表达降低（0．35±0．08对0．78±0．11，0．34±0．07对0．77±0．08，均P〈0．05），心肌磷酸化AMPK-α和Glurr4蛋白表达降低（0．47±0．12对0．72±0．10，0．41±0．09对0．79±0．08，均P〈0．05）。与糖尿病组比较，替米沙坦治疗12周后心室重／体重降低[（3．49±0．39对4．38±0．07）g／kg，P〈0．05]，心功能改善，血浆和心肌脂联素水平升高[（1．41±0．02对1．09±0．03）μg／ml，（0．16±0．01对0．12±0．02）μg／mg蛋白，均P〈0．05]，心肌脂联素受体1mRNA和蛋白表达增加（0．48±0．06对0．35±0．08，0．47±0．09对0．34±0．07，均P〈0．05），心肌磷酸化AMPK—α和GluT4表达水平均升高（0．57±0．10对0．47±0．12，0．52±0．10对0．41±0．09，均P〈0．05）。结论糖尿病大鼠心肌脂联素及其受体1的表达水平降低。替米沙坦上调糖尿�Objective To observe the effects of telmisartan on the expression of cardiac adiponectin and its receptor 1 in diabetic rats, and to investigate the protective roles and mechanisms of telmisartan on cardiomyopathy of diabetic rats. Methods Thirty male Wistar rats were randomly divided into control group, diabetic group, and telmisartan group. Diabetes mellitus was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin. After establishment of diabetes model, telmisartan （5 mg · kg^-1 · d^-1 ） was administered by lavage for 12 weeks in telmisartan group. At termination, the cardiac function was detected. Plasma and myocardial adiponectin levels were assayed by enzyme immunoassay mRNA expression of adiponectin receptor 1 （ adipoR1 ） was assayed by RT-PCR, and protein expression of adipoR1, phosphorylated- AMPK-α, and glucose transporter 4 （GluT4） were determined by Western blotting in myocardium. Results After 12 weeks, the ratio of heart to body weight was increased [ （4.38±0.07 vs 2.99±0.67） g/kg, P〈0.05 ], but adiponectin levels in plasma and myocardium were decreased [ （1.09±0.03 vs 1.87±0.05 ）μg/ml, （0.12±0.02 vs 0. 21±0.02）μg/mg protein, both P〈0.05 ] in diabetic rats. In myocardium of diabetic rats, the protein and mRNA of adipoR1 were also decreased （0.35±0.08 vs 0. 78±0.11, 0.34±0.07 vs 0. 77±0.08, both P〈0.05 ） , so were the expressions of phosphorylated-AMPK-α and GluT4 （0.47±0.12 vs 0. 72±0.10, 0.41±0.09 vs 0. 79±0.08, both P〈0.05 ）. The cardiac function was also significantly decreased in diabetic group. The ratio of heart to body weight was significantly decreased in telmisartan group [ （3.49±0.39 vs 4.38±0.07） g/kg, P〈0.05 ]. Both of plasma and myocardial adiponectin levels were increased [ （ 1.41 ±0.02 vs 1.09±0.03 ） μg/ml, （0.16±0.01 vs 0.12±0.02） μg/mg protein, P〈0.05 ] , as well as mRNA （0.48±0.06 vs 0. 35±0.08） and protein expression of adipoR1 （0.47±0. 09 vs

关 键 词：替米沙坦 糖尿病 实验性 脂联素受体1 心肌病 

分 类 号：R587.1[医药卫生—内分泌]