Exendin-4对肥胖大鼠内皮依赖性血管舒张功能的作用研究  

Exendin-4 Improves Impaired Endothelial Dependent Vasodilation in Obese Rat

作　　者：韩丽娜[1] 余叶蓉[1] 王犇[1] 

机构地区：[1]四川大学华西医院内分泌代谢科,成都610041

出　　处：《四川大学学报（医学版）》2013年第1期49-52,共4页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(No.81070675)资助

摘　　要：目的研究肽类肠道激素高血糖素样肽1(GLP-1)类似物艾塞那肽(exendin-4,Ex-4)对高脂饲料诱导的肥胖大鼠内皮依赖性血管舒张功能的影响。方法将20只雄性Wistar大鼠随机分成2组(每组10只),正常对照组给予普通饲料喂养,肥胖组给予高脂饲料。观察各组动物体质量变化,10周后处死大鼠,采集心脏血液,检测血浆生化指标,计算体脂比,分离出主动脉置于器官浴槽中,肥胖组血管环分为肥胖Ex-4组与空白对照组两亚组(每组10个血管环)。肥胖Ex-4组血管环以Ex-4加Krebs-Henseleit液(K-H液)孵育,正常对照组及肥胖空白对照组以K-H液孵育,加入不同浓度的乙酰胆碱和硝普钠,观察各组血管环内皮依赖性与非内皮依赖性血管舒张功能。结果肥胖组动物脂代谢紊乱,血浆甘油三酯、总胆固醇及游离脂肪酸浓度较正常对照组升高(P<0.01),腹腔脂肪质量及体脂比均高于正常对照组(P<0.05)。与正常对照组相比,肥胖大鼠内皮依赖性血管舒张功能受损(P<0.05)。肥胖Ex-4组大鼠内皮依赖性血管舒张功能较肥胖空白对照组改善(P<0.05)。3组间非内皮依赖性血管舒张功能差异无统计学意义(P>0.05)。结论 Ex-4对肥胖大鼠血管受损的内皮细胞具有确切的保护作用。Objective To determine whether exendin-4 （Ex-4）might improve endothelial dysfunction in aorta isolated from high-fatty diet induced obese rats. Methods 20 male Wistar rats were divided into normal control and high-fat supplement （OB） groups （n ： 10 for each group）. The rats were sacrificed after 10 weeks feeding and fhoracic aorta was dissected and cut into four rings of 3 mm length, the response to acethylcholine （Ach） and sodium nitroprusside （SNP） were examined in organ bath containing Krebs-Henseleit （K-H） solution. In order to study the direct effects of Ex-4 on obese rats vascular function, the aortic rings obtained from obese rats were incubated with K-H solution （OBC group, n=10）,or with K-H solution plus Ex-4 （OI3-Ex group, n=10）. Aortic rings obtained from normal control group （n： 10） were incubated with K-H solution. After I hour of incubation, the aortic rings were precontracted with norepinephrine （0.1 μmol/L）, then the rings were exposed to cumulative concentration of Ach （10-9-10-4 mol/L）or sodium SNP （10-10-10-6 mol/L） to test the endothelial dependent （EDV） and independent vasodilation （EIV）. The blood plasma of the rats was collected for biochemical test and celiac fat and body mass data were also obtained. Results The levels of serum triglyceride, total cholesterol, and free fat acid were elevated in the obese group compared with that of normal control group （P^0.01）. The ratio of celiac fat and body mass in the obese rats was also higher than the control （P〈O. 05）. Ach caused a concentration dependent vascular relaxation in all preconstricted aortic rings. Compared to the control group, maximal endothelium dependent relaxation in the obese group was impaired （P〈0.05）. The EIV values were comparable between two groups. Pre-incubation of obese rat＇s vessels with Ex-4 significantly increased cumulative relaxation to Ach （P〈0.05）. SNP induced vessels relaxation had no statistical significance each groups （P〉0.

关 键 词：肥胖 高血糖素样肽1 艾塞那肽 内皮依赖性血管舒张功能 

分 类 号：R589.2[医药卫生—内分泌]