p38MAPK/eNOS信号通道在胰高血糖素样肽-1抑制AGEs诱导的人脐静脉内皮细胞凋亡中的作用  

Role of p38MAPK/e NOS signaling pathway in the inhibition of AGEs-induced apoptosis of human umbilical vein endothelial cells by glucagon-like peptide-1

作　　者：曾海龙[1] 黄志秋[1] 张艺能 孙慧琳[1] 

机构地区：[1]广东药学院附属第一医院内分泌科,广东广州510080 [2]广东药学院附属第一医院科教科,广东广州510080

出　　处：《南方医科大学学报》2016年第1期116-119,139,共5页Journal of Southern Medical University

基　　金：广东省自然科学基金(S2011010002074);清远市科技计划项目(2011B011112044)

摘　　要：目的探讨p38MAPK信号通道在胰高血糖素样肽-1(GLP-1)拮抗糖基化终末产物(AGEs)诱导的人脐静脉内皮细胞凋亡的作用。方法实验组分为对照组、AGEs组、GLP-1组、AGEs+GLP-1组、AGEs+抑制剂组及AGEs+GLP-1+抑制剂组,western blot技术检测p-p38MAPK/p38MAPK、p-e NOS/e NOS蛋白表达情况,Annexin V/PI流式检测细胞凋亡率。结果与对照相比较,单独加入AGEs或GLP-1可分别导致p-p38MAPK蛋白表达水平明显上升(P=0.001)或下降(P<0.001);与对照组相比AGEs可显著降低p-e NOS表达水平(P=0.007),而予以GLP-1或p38MAPK抑制剂(SB203580)预处理后,受抑制的e NOS蛋白表达水平再次显著升高(P=0.004);在AGEs组加入SB203580或GLP-1预处理后,AGEs诱导的细胞凋亡率均显著下降(P<0.001,P<0.001)。结论 GLP-1至少部分通过抑制p38MAPK蛋白磷酸化,上调磷酸化e NOS蛋白的表达,对人脐静脉内皮细胞起到抗凋亡的保护作用。Objective To investigate the role of p38 MAPK signaling pathway in the mechanism by which glucagon-like peptide-1（GLP- 1） inhibits endothelial cell damage induced by AGEs. Methods Human umbilical vein endothelial cells were divided into control group, AGEs group, GLP-1 group, AGEs＋GLP-1 group, AGEs＋inhibitor group, and AGEs＋GLP-1＋inhibitor group.The expressions of p- p38MAPK/p38 MAPK and p- e NOS/e NOS protein were examined by Western blotting, and the cell apoptosis rates were tested by flow cytometry. Results Compared with the control group, AGEs significantly enhanced the expression of p- p38 MAPK protein（P=0.001） while GLP- 1 significantly inhibited its expression（P0.001）. AGEs significantly inhibited the expression of p-e NOS protein（P=0.007）, which was enhanced by GLP-1 and p38 MAPK inhibitor（SB203580）（P=0.004）. Both SB203580 and GLP- 1 treatment decreased the apoptosis rate of AGEs- treated cells（P0.001）. Conclusion GLP- 1can protect human umbilical vein endothelial cells against AGEs- induced apoptosis partially by inhibiting the phosphorylation of p38 MAPK protein and promoting the expression of p-e NOS protein.

关 键 词：胰高血糖素样肽-1 P38MAPK 人脐静脉内皮细胞 内皮细胞损伤 糖基化终末产物 

分 类 号：R587.1[医药卫生—内分泌]