血管紧张素Ⅱ对血管平滑肌细胞迁移的影响及分子机制  

The Effect and Molecular Mechanism of Ang Ⅱ on Vascular Smooth Muscle Cells Migration

作　　者：帅维 张伟[1] 范致星 Shuai Wei;Zhang Wei;Fan Zhixing(Department of Cardiology,Renmin Hospital of Wuhan University,Wuhan 430061,China)

机构地区：[1]武汉大学人民医院心血管内科,湖北武汉430061

出　　处：《巴楚医学》2021年第1期6-10,共5页Bachu Medical Journal

基　　金：国家自然科学基金项目(No:81800258)。

摘　　要：目的:探讨血管紧张素Ⅱ(AngⅡ)对血管平滑肌细胞(VSMCs)迁移的影响及AngⅡ-1型受体(AT1R)依赖的PI3K/Akt信号通路介导的分子机制。方法:体外分离培养大鼠胸主动脉VSMCs,分为Control对照组、AT1R siRNA转染组、Control siRNA转染组和PI3K抑制剂(LY294002)干预组,观察AngⅡ对VSMCs迁移的影响;RT-PCR检测AT1R mRNA表达水平;Western blot检测AT1R、Akt、p-Akt、PI3K蛋白表达水平;ELISA测定PI3K的活性。结果:AngⅡ(0.1~1000 ng/mL)可明显促进VSMCs迁移(P<0.05),AngⅡ浓度为100 ng/mL时促迁移效应最显著,且对VSMCs无细胞毒性作用。AngⅡ(100 ng/mL)处理后,VSMCs中PI3K活性及Akt磷酸化水平明显增加(均P<0.05)。经AT1R siRNA转染或PI3K抑制剂干预,PI3K/Akt的活化和AngⅡ介导的VSMCs迁移被明显抑制(均P<0.05)。结论:AngⅡ呈剂量依赖性促进VSMCs迁移,AT1R依赖的PI3K/Akt信号通路参与了此过程。Objective:To investigate the effect of angiotensinⅡ(AngⅡ)on the migration of vascular smooth cells(VSMCs),and explore the role of AngⅡ-type 1 receptor(AT1R)-dependent PI3K/Akt pathway in this process.Methods:Primary VSMCs were isolated from the thoracic aorta of male SD rats and cultured in vitro.Cells were divided into the Control group,the AT1R siRNA transfected group,the Control siRNA transfected group and the PI3K inhibitor(LY294002)intervention group,to observed the effect of AngⅡon VSMCs migration.Expression of AT1R mRNA was detected by RT-PCR,protein expression of AT1R,Akt,p-Akt and PI3K were detected by Western blot.The activity of PI3K was determined by ELISA.Results:AngⅡ(0.1 to 1000 ng/mL)obviously promoted VSMCs migration(P<0.05),the most significant pro-migration effect was at the concentration of 100 ng/mL,without any cytotoxic effects on VSMCs.PI3K activity and Akt phosphorylation levels were significantly increased in VSMCs induced by AngⅡat the concentration of 100 ng/mL(both P<0.05).Pretreated with AT1R siRNA or the PI3K inhibitor LY294002 markedly blocked PI3K/Akt pathway activation and VSMCs migration under the stimulation of AngⅡ(all P<0.05).Conclusion:AngⅡcould enhance VSMCs migration in a dose-dependent manner,and AT1R-dependent PI3K/Akt signaling pathway may participate in this process.

关 键 词：血管紧张素Ⅱ AngⅡ-1型受体 PI3K/AKT信号通路 血管平滑肌细胞 

分 类 号：R543.5[医药卫生—心血管疾病]