艾塞那肽对同型半胱氨酸诱导的人脐静脉内皮细胞氧化损伤的保护作用及其潜在机制  

Protective effect and its underlying mechanism of exenatide on human umbilical vein endothelial cell oxidative damage induced by homocysteine

作　　者：马世凤[1] 洪天配[1] 魏蕊[1] 刘烨[1] 杨进[1] 张琳[1] 王广[1] 

机构地区：[1]北京大学第三医院内分泌科,100191

出　　处：《中国糖尿病杂志》2013年第4期345-348,共4页Chinese Journal of Diabetes

基　　金：国家自然科学基金资助项目(81070701;81270858;81000315);高等学校博士学科专项科研基金资金项目(20100001110083;20120001120069);国家973计划资助项目(2012CB517502)

摘　　要：目的观察艾塞那肽对同型半胱氨酸(Hcy)所诱导的内皮细胞氧化损伤的保护作用,并探讨其潜在的机制。方法体外分离和培养人脐静脉内皮细胞(HUVECs),艾塞那肽预处理1h后,加入Hcy、艾塞那肽和/或exendin(9-39)共同孵育24h。利用激光共聚焦显微镜技术检测细胞内活性氧簇(ROS)和一氧化氮(NO)的水平,采用Western印迹检测内皮型一氧化氮合酶(eNOS)和磷酸化eNOS(p-eNOS,Ser1177)的表达。结果与NC组相比,Hcy组的细胞内ROS水平平均增加54%,NO水平平均下降34%(P均<0.05);艾塞那肽不仅可逆转Hcy所致的细胞内ROS水平增高和NO水平降低,而且可依赖性上调p-eNOS的表达;胰升血糖素样肽-1(GLP-1)受体阻滞剂exendin(9-39)可消除部分艾塞那肽的上述效应。结论艾塞那肽可上调eNOS的磷酸化,并且对Hcy所致的内皮细胞氧化损伤具有保护作用,艾塞那肽的上述作用至少部分是GLP-1受体依赖性的。Objective To investigate the protective effect of exenatide on the endothelial cell oxidative damage induced by homocysteine （Hcy） and to explore its underlying mechanism. Methods The in-vitro isolated human umbilical vein endothelial cells （HUVECs） were pre-incubated with exenatide for 1 h and then incubated with Hcy, exenatide and/or exendin （9-39） for 24 h. A confocal laser scanning microscope was used to detect the levels of intracellular reactive oxygen species （ROS） and nitric oxide （NO）. The expression of endothelial nitric oxide synthase （eNOS） and phosphorylated eNOS （p-eNOS, Ser1177） was detected by Western blot. Results Compared with the control group, the intracellular level of ROS was increased by 54% and the intracellular level of NO was reduced by 34% in the Hcy- treated group （both P〈0. 05）. Exenatide not only significantly reversed the increment of ROS generation and the reduction of NO production induced by Hcy treatment, but also dose-dependently upregulated the expression of p-eNOS. The above effects of exenatide were partly abolished by adding the glucagon-like peptide-1 （GLP-1） receptor antagonist exendin （9-39）. Conclusion Exenatide activates the phosphorylation of eNOS and therefore has protective effect on the vascular endothelial cell oxidative damage induced by Hcy. All these effects of exenatide are at least in part dependent on GLP-1 receptor.

关 键 词：艾塞那肽 同型半胱氨酸 血管内皮 氧化应激 

分 类 号：R96[医药卫生—药理学]