艾溴利平对糖尿病小型猪心肌组织蛋白激酶-B表达的影响  

Effect of ibrolipim on expression of protein kinase-B in myocardium of diabetic miniature pigs

作　　者：魏寒松[1] 陈安平[2] 余坚[3] 李宏光[1] 刘毅[1] 易光辉[2] 尹卫东[2] 王宗保[3] 

机构地区：[1]南华大学生物化学与分子生物学研究所,湖南衡阳421001 [2]南华大学实验动物学部,湖南衡阳421001 [3]南华大学心血管病研究所,湖南衡阳421001

出　　处：《中国新药与临床杂志》2008年第10期727-731,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：湖南省科技厅科研项目(2006TP3015)

摘　　要：目的观察磷脂酰肌醇-3激酶信号通路中关键分子蛋白激酶-B(Akt2)在饮食诱导的糖尿病小型猪心肌组织中的表达,以及合成化合物艾溴利平对Akt2表达的影响,探讨艾溴利平在糖尿病心肌病变中的作用。方法15只雄性广西巴马小型猪按体重随机分为3组,每组5只。正常对照组饲正常饲料,高能量组饲高脂高糖高胆固醇饲料,加药组在高脂高糖高胆固醇饲料中加入艾溴利平(0.4 g·kg^(-1)·d^(-1))。每月末测定血糖、三酰甘油(TG)、胰岛素、高密度脂蛋白胆固醇(HDL-C)并行口服葡萄糖耐量实验(OGTF)。5 mo末取部分心肌组织,用Western blotting和免疫组织化学方法检测Akt2蛋白的表达。结果与正常对照组相比,高能量组血糖、TG、胰岛素和HDL-C升高,糖耐量减低;加药组与高能量相比,血糖、TG和胰岛素明显降低,HDL-C水平升高,OGTF血糖清除和胰岛素分泌近似正常对照组。心肌组织Akt2蛋白表达量正常对照组为1.48±s 0.22,明显高于高能量组(1.00±0.16,P<0.01);而加药组Akt2蛋白表达量1.38±0.20,高于高能量组(P<0.01),与正常对照组相近(P>0.05)。结论高脂高糖高胆固醇饮食诱导的糖尿病小型猪心肌组织Akt2表达降低,艾溴利平能够上调心肌组织Akt2蛋白的表达。AIM diabetic minipigs induced To observe the change of protein kinase-B by high-fat/high-sucrose/high-cholesterol lipase （LPL） activator ibrolipim on the protein expression of Akt2. minipigs were randomized into three groups： control group （n = 5, with （Akt2） expression in myocardium of to investigate the effect of lipoprotein METHODS Fifteen Guangxi Bama the normal control diet）, high calorie group （n = 5, with the high-fat/high-sucrose/high-cholesterol diet）, and high calorie＋ibrolipim group （n = 5 with the high calorie supplemented with ibrolipim, 0.4 g·kg^-1·d^-1） . Plasma glucose, triglyceride, insulin and high density lipoprotein-cholesterol and oral glucose tolerance test （OGTF） were carried out each month following overnight fasting. The pigs were sacrificed at the end of mo 5. Cardiac muscle was obtained for histological preparations, the protein expression of Akt2 in myocardium was measured by Western blotting and immunohistochemistry. RESULTS Comparing with control group, the levels of plasma glucose, triglyceride, insulin and high density fipoprotein-cholesterol were evidently increased in the high calorie group, but with impaired glucose tolerance. After supplementing ibrolipim into high calorie, the concentration of plasma glucose, triglyceride and insulin obviously decreased in comparing with the high calorie group, but high density lipoprotein-cholesterol increased with repair of glucose tolerance. The protein expression of Akt2 decreased in myocardium of high calorie group, but increased in ibrolipim group. CONCLUSION Ibrolipim can up-regulate the protein expression of Akt2 in myocardium of diabetic minipigs induced by the high-fat/high-sucrose/high-cholesterol diet by lowering the levels of plasma glucose, triglyceride and insulin with simultaneous increase of high density lipoprotein-cholesterol and improvement of glucose tolerance.

关 键 词：糖尿病 心肌疾病 蛋白质丝氨酸苏氨酸激酶 猪 艾溴利平 

分 类 号：R972.6[医药卫生—药品]