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

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-eNOS/eNOS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-eNOS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eNOS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eNOS蛋白的表达，对人脐静脉内皮细胞起到抗凋
亡的保护作用。

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

Objective To investigate the role of p38MAPK 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/p38MAPK and p-eNOS/eNOS 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 (P<0.001). AGEs
significantly inhibited the expression of p-eNOS 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 (P<0.001).
Conclusion GLP-1 can protect human umbilical vein endothelial cells against AGEs-induced apoptosis partially by inhibiting
the phosphorylation of p38MAPK protein and promoting the expression of p-eNOS protein.