血管紧张素Ⅱ诱导人脐静脉内皮细胞增殖的分子机制  

The Molecular Mechanism of the Proliferation of Human Umbilical Vein Endothelial Cells Induced by Angiolensin Ⅱ

作　　者：李健[1] 崔进[1] 姚树明[1] 刘湉[1] 胡忆[1] 王殿华[1] 

机构地区：[1]昆明医学院天然药物药理重点实验室,昆明650031

出　　处：《昆明医学院学报》2005年第2期32-37,共6页Journal of Kunming Medical College

基　　金：云南省自然科学基金项目(2001C0047M)

摘　　要：目的:探讨AngⅡ诱导人脐静脉内皮细胞增殖的分子机制.方法:体外培养人脐静脉内皮细胞株,分为AngⅡ处理组、NAC干预组和正常对照组.采用各种生物化学方法观察不同浓度AngⅡ在不同时间对人脐静脉内皮细胞的增殖率和细胞产生ROS(·OH)的量.应用基因芯片技术检测人脐静脉内皮细胞增殖作用的相关基因表达谱.结果:一定浓度的AngⅡ作用12h时人脐静脉内皮细胞增殖率增加(P<0·05);ROS(·OH)的含量与人脐静脉内皮细胞增殖率呈显著负相关;NAC可以减少人脐静脉内皮细胞ROS(·OH)的含量,明显抑制AngⅡ对人脐静脉内皮细胞的增殖作用;0·0625μmol/LAngⅡ作用人脐静脉内皮细胞12h时,与细胞增殖相关的ERK、CDK、CCN、PCNA等25个基因普遍上调,而与细胞凋亡相关的DR6、Caspas-es6、BAK1、PDCD8等12个基因普遍下调,在1μmol/LAngⅡ作用12h时,呈相反结果.结论:AngⅡ可诱导人脐静脉内皮细胞产生ROS(·OH),引起多种与人脐静脉内皮细胞增殖相关的靶基因表达;ROS(·OH)可能是AngⅡ诱导人脐静脉内皮细胞增殖的主要信号转导分子和基因表达调节分子.Objective: To explore the molecular mechanism of the proliferation of human umbilical vein endothelial cells induced by AngⅡ.Methods: The lines of human umbilical vein endothelial cell cultured in vitro were divided into 3 groups which were treated by AngⅡ, AngⅡ+NAC, and normal culture medium respectively. First we observed the proliferous effect of human umbilical vein endothelial cells induced by AngⅡ at different concentration at different time with biochemical methods. Then the contents of ROS(·OH) in 3 groups were detected by spectrophotometer. Finally we detected the related gene expression in the process of human umbilical vein endothelial cells proliferation via the technique of genechips.Results: Human umbilical vein endothelial cells incubated with AngⅡ(0.03125～1μmol/L ) for 12 hours increased the proliferation rate (P<0.05);the negative correlation between proliferation rate and the contents of ROS(·OH)(r=-0.8, P<0.01) was significant;NAC can reduce the content of ROS(·OH) and inhibit the proliferation of human umbilical vein endothelial cells;The technique of genechips analysis suggests that the genes expression related to proliferation such as ERK, Akt, CCN and PCNA increased, while the gene expression related to apoptosis such as DR6, Caspases6 BAK1 and PDCD8 decreased when human umbilical vein endothelial cell were induced by AngⅡ(0.0625μmol/L) for 12 hours; In contrast, when human umbilical vein endothelial cells were induced by AngⅡ(1μmol/L) for 12 hours, we can obtain reverse results. Conclusion: Human umbilical vein endothelial cells induced by AngⅡcan produce ROS(·OH).The target gene expression related to proliferation of human umbilical vein endothelial cells may be mediated by ROS(·OH), ROS(·OH) may be the molecules which play an important role in the signal transduction and gene expression of proliferation.

关 键 词：内皮细胞增殖 分子机制 血管紧张素Ⅱ 人脐静脉内皮细胞 静脉内皮细胞株 相关基因表达谱 细胞增殖率 细胞增殖作用 生物化学方法 抑制AngⅡ 基因表达调节 信号转导分子 正常对照组 mol/L 靶基因表达 体外培养 技术检测 

分 类 号：R732.2[医药卫生—肿瘤] R735.7[医药卫生—临床医学]