内皮细胞转分化

汤日宁戴厚永李青吕林莉张建东马坤岭刘必成

【摘要】目的探讨高糖对内皮细胞转分化的影响及其与血管紧张素Ⅱ(ATⅡ)的关系。方法将人主动脉内皮细胞分成正常浓度葡萄糖(NG)组、高糖(HG)组和厄贝沙坦干预(HG+Irb)组。放射免疫法检测细胞上清液中ATⅡ的浓度。共聚焦显微镜观察CD31和成纤维细胞特异蛋白1(FSP1)的双染色结果。Western blot检测FSP1蛋白水平的表达。结果与NG组比，高糖刺激的内皮细胞导致ATⅡ和FSP1表达增加(P<0.05)，呈浓度和时间依赖性。共聚焦显微镜可见CD31和FSP1表达重叠，且一些细胞获得纺锤样的改变并失去CD31染色。厄贝沙坦可抑制高糖引起的上述改变(P<0.05)。结论高糖可能通过ATⅡ介导的内皮细胞转分化导致内皮细胞损伤，而厄贝沙坦抑制内皮细胞转分化。

【关键词】高糖;内皮细胞转分化;血管紧张素Ⅱ;厄贝沙坦

doi:10.3969/j.issn.1006-6187.2011.05.013

Angiotesin Ⅱ mediates the high glucose-induced endothelial-to-mesenchymal transition in human aortic endothelial cells

TANG Ri-ning, DAI Hou-yong, LI Qing, et al. Institute of Nephrology, Zhongda Hospital, Southeast University, Nanjing 210009, China

Corresponding author: LIU Bi-cheng,E-mail:liubc64@yahoo.com.cn

【Abstract】ObjectiveThe aim was to investigate the influence of high glucose on endothelial to mesenchymal transition (EndMT) and its relevance with the activation of angiotensin Ⅱ.MethodsHuman aortic endothelial cells (HAEC) were divided into three groups: normal glucose group (NG), high glucose group (HG) and the Irbesartan (1μmol/L) treated group. The concentration of angiotensin Ⅱ in the HAEC supernatant was detected by radioimmunoassay. Immunofluorescence staining was performed to detect the co-expression of CD31 and fibroblast specific protein1 (FSP1).ResultsHG led to a significant increase of expression of angiotensin Ⅱ and FSP1 protein in HAEC in dose and time dependent manner. Double staining of HAEC showed co-localization of CD31 and FSP1. These changes were inhibited by treatment with irbesartan (P<0.05).ConclusionThese findings suggest a novel mechanism on the high glucose HG induced endothelial damage through angiotensin II mediated EndMT, which is inhibited by irbesartan.

【Key words】High glucose; Endothelial-to-mesenchymal transition; Angiotensin Ⅱ; Irbesartan