阿托伐他汀下调活性caspase-9／caspase-3的表达抑制H2O2诱导的血管内皮细胞凋亡  

Atorvastatin inhibits the H2O2 -induced apoptosis of human vascular endothelial cells through a down-regulation of cleaved caspase-9/caspase-3

作　　者：徐哲荣[1] 姚航平[2] 李素军[1] 吴薇珍[1] 杨云梅[1] 

机构地区：[1]浙江大学医学院附属第一医院老年病科,杭州310003 [2]传染病诊治国家重点实验室

出　　处：《中华医学杂志》2012年第24期1711-1714,共4页National Medical Journal of China

基　　金：浙江省教育厅科研基金（ZC200804919）;浙江省中医药管理局科研基金（2008CB034）

摘　　要：目的探讨阿托伐他汀在过氧化氢（H2O2）诱导的血管内皮细胞凋亡中的作用，以及内在分子机制。方法采用H2O2（100μmol／L）损伤ECV-304细胞18h建立细胞凋亡模型，予以不同浓度阿托伐他汀（0．1、1和10μmol／L）预处理2h，利用荧光显微镜观察细胞形态变化，MTT检测细胞活性，流式细胞技术测定凋亡细胞比例，最后采用Western印迹方法检测活性片段caspase-3和caspase-9的表达。结果H2O2损伤导致ECV-304细胞发生明显的凋亡形态学改变，细胞活性显著下降，凋亡细胞比例高达50．71％。经过不同浓度阿托伐他汀预处理后，细胞活性明显恢复，凋亡细胞比例显著减少（39．45％、20．53％和7．83％）。Western印迹检测发现，H2O2损伤组caspase-3和caspase-9活性片段表达非常明显，阿托伐他汀预处理后，两者表达水平下降，并且呈现明显的剂量依赖性。结论阿托伐他汀具有抑制H2O2诱导的血管内皮细胞凋亡的作用，并且这一作用呈现剂量依赖性；caspase-9／caspase-3活性片段表达水平降低与阿托伐他汀的这一保护作用有关。Objective To investigate the effect and potential mechanism of atorvastatin against H2 P2-induced apoptosis of human umbilical vein endothelial cells （ECV-304）. Methods ECV-304 cells were pretreated with different concentrations of atorvastatin （0. 1, 1 and 10 μmol/L） for 2 h, followed by an exposure to 100 μmoL/L H2O2 for 18 h. Cellular morphology was observed under fluorescence microscope. Cellular viability and apoptosis were evaluated by methyl thiazolyl tetrazolium （MTF） and flow cytometry. Finally the expressions of cleaved caspase-3 and caspase-9 were measured by Western blot. Results H2O2 treatment caused an obvious apoptosis of ECV-304 ceils and significantly decreased the cellular viability as characterized by a high percentage （ 50. 71% ） of apoptotic cells. Atorvastatin pretreatment inhibit cellular apoptosis induced by H202 （39.45%, 20. 53% and 7.83%）. Western blot assay showed that H202 treatment caused a high expression of cleaved caspase-3 and caspase-9 while atorvastatin pretreatment obviously inhibited the expression in a dose-dependent manner. Conclusions Atorvastatin inhibits the H2 O2-induced apoptosis of ECV-304 cells in a dose-dependent manner. This effect may be associated with the down-regulation of cleaved caspase-9/caspase-3.

关 键 词：细胞凋亡 半胱氨酸天冬氨酸蛋白酶 阿托伐他汀 血管内皮细胞 

分 类 号：R96[医药卫生—药理学]