ANG Ⅱ诱导大鼠动脉内皮细胞凋亡作用分子机制研究  

Study on the molecular mechanism of AngiotensinⅡ-induced apoptosis in rat arterial endothelial cell

作　　者：周春刚[1] 陆曙[1] 王书乐[1] 张志斌[1] 

机构地区：[1]南京中医药大学无锡附属医院中心实验室,江苏无锡214001

出　　处：《中国实验诊断学》2013年第9期1563-1566,共4页Chinese Journal of Laboratory Diagnosis

基　　金：江苏省中医药局科技项目(LZ09099)

摘　　要：目的探讨ANGⅡ诱导大鼠动脉内皮细胞凋亡的分子机制。方法体外培养大鼠动脉内皮细胞株(RAOEC),通过ANGⅡ诱导RAOEC凋亡,采用流式细胞仪检测ANGⅡ诱导凋亡改变,RT-PCR荧光相对定量检测相关凋亡蛋白mRNA水平变化,组间差异统计性分析采用Students T-test。结果 ANGⅡ诱导大鼠动脉内皮凋亡作用具有时间和剂量依赖性,高浓度和低浓度或者延长作用时间都不能增加凋亡率,血管紧张素特异性的受体拮抗剂缬沙坦和PD123319联合应用能够完全抑制ANGⅡ诱导RAOEC细胞凋亡作用,单独应用均不能完全抑制凋亡。与空白对照组比较,ANGⅡ组AT1R和AT2R mRNA水平显著上调,胞外死亡受体途径相关促凋亡分子Fas、FasL caspase 8mRNA表达水平上调,胞内线粒体途径促凋亡分子BAX、caspase 9mRNA显著上调,差异具有统计学意义(P<0.05)。结论 ANGⅡ诱导RAOEC细胞凋亡具有剂量和时间依赖性,其机制可能是由AT1R和AT2R受体介导通过胞外死亡受体途径和胞内线粒体途径共同参与的信号转导机制。Objective To investigate the molecular mechanism of apoptosis induced by Angiotensin II in rat arterial endothelial cell Iine（RA（）EC）. Methods The RAOEC were cultured in vitro in the presence or absence of ANGII ,de tection of apoptosis were used flow cytometry,the expression of apoptosis-related proteins mRNA were detected by Re al-Time PCR. The data were analyzed for the significant difference by Students T test. Results ANG II induced RAO EC apoptosis in a dose-and time-dependent manner. The proapoptotic effect were attenuated by the ANG II receptor specific antagonist valsartan or PD123319 and was completed blocked by incubation with the combined antagonists. Compared with control group, the expression of AT1R and AT2R mRNA were significantly upregulated in ANG II group,ANG II significantly upregulated the expression of Fas /FasL and caspase 8 mRNA in the extrinsic apoptotic pathway,meanwhile increased the level of caspase 8 and BAX mRNA in the intrinsic apoptotic pathway （P〈0.05）. Conclusion ANG II induced RAOEC apoptosis in a dose and time-dependent manner, these study suggest that ANG II induced apoptosis in RAOEC required both the AT1R and AT2R through the extrinsic and intrinsic apoptotic pathway.

关 键 词：血管紧张素Ⅱ 动脉内皮细胞 凋亡 

分 类 号：R363[医药卫生—病理学]