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p38 MAPK通路介导胰高血糖素样肽-1对人脐静脉内皮细胞凋亡的抑制

徐华, 李海龙, 牛自勇, 李桂忠, 曹军, 姜怡邓

宁夏医科大学基础医学院病理生理学系,银川 750004;宁夏第三人民医院内科,银川 750021

摘要

本文旨在探讨胰高血糖素样肽-1 (glucagon-like peptide-1, GLP-1)对棕榈酸盐诱导的人脐静脉内皮细胞(human umbilical vein endothelial cells, HUVECs)凋亡的影响及其机制。体外培养HUVECs,用棕榈酸盐诱导其凋亡,同时加入GLP-1干预。酶联接免疫吸附剂测定(enzyme-linked immunosorbnent assay, ELISA)法分别测定Caspase-3活性和DNA碎片含量,Western blot测定磷酸化细胞丝裂原活化蛋白激酶(phospho-p38 mitogen-activated protein kinase, p-p38 MAPK)表达。结果显示,与对照组相比,棕榈酸盐处理的HUVECs中Caspase-3活性和DNA碎片含量显著增多;而GLP-1可呈剂量依赖性降低棕榈酸盐所诱导升高的Caspase-3活性和DNA碎片。另外,GLP-1显著抑制由棕榈酸盐诱导的HUVECsp-p38 MAPK表达上调。以上结果提示,GLP-1可以抑制棕榈酸盐诱发的HUVECs脂性凋亡,其机制可能是对p-p38 MAPK表达的下调。

关键词: 胰高血糖素样肽-1; 人脐静脉内皮细胞; p38 MAPK; 凋亡

分类号:R363.2

[Involvement of p38 MAPK pathway in GLP-1-induced inhibition of apoptosis in human umbilical vein endothelial cells.] [Article in Chinese]

XU Hua, LI Hai-Long, NIU Zi-Yong, LI Gui-Zhong, CAO Jun, JIANG Yi-Deng

Department of Pathophysiology, Ningxia Medical University, Yinchuan 750004; Department of Internal Medicine, Ningxia Third Hospital, Yinchuan 750021

Abstract

The aim of the present study was to investigate the effect of glucagon-like peptide-1 (GLP-1) on palmitate-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and the underlying mechanism. HUVECs were cultured in vitro, and then treated by palmitate to induce apoptosis. Meanwhile, GLP-1 was added to explore its effect. After 24 h of the treatments, Caspase-3 activity and DNA fragmentation were measured using ELISA kits. Phospho-p38 mitogen-activated protein kinase (p-p38 MAPK) expression was detected by Western blot. The results showed that incubating HUVECs with 0.125 mmol/L GLP-1 increased Caspase-3 activity and DNA fragmentation. GLP-1 significantly inhibited palmitate-induced increases of Caspase-3 activity and DNA fragmentation in a concentration-dependent manner. Moreover, GLP-1 inhibited the up-regulation of p-p38 MAPK expression induced by palmitate in HUVECs. These results suggest GLP-1 protects HUVECs against lipo-apoptosis, and this effect may be mediated through inhibiting p38 MAPK pathway.

Key words: glucagon-like peptide-1; human umbilical vein endothelial cells; p38 MAPK; apoptosis

收稿日期:2012-02-28  录用日期:2012-05-28

通讯作者:曹军,姜怡邓  E-mail: jwcjyd@163.com, CAO Jun: Tel: +86-951-6980093

引用本文:

徐华, 李海龙, 牛自勇, 李桂忠, 曹军, 姜怡邓. p38 MAPK通路介导胰高血糖素样肽-1对人脐静脉内皮细胞凋亡的抑制[J]. 生理学报 2012; 64 (4): 444-448.

XU Hua, LI Hai-Long, NIU Zi-Yong, LI Gui-Zhong, CAO Jun, JIANG Yi-Deng. [Involvement of p38 MAPK pathway in GLP-1-induced inhibition of apoptosis in human umbilical vein endothelial cells.] [Article in Chinese]. Acta Physiol Sin 2012; 64 (4): 444-448 (in Chinese with English abstract).