阿托伐他汀通过调节Bcl-2/Bax蛋白表达延缓血管内皮细胞衰老
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国家973重点基础研究发展规划基金资助项目(2007CB507405);中华医学会临床医学科研专项资金-动脉粥样硬化研究资金资助(09010530208);辽宁省科学技术研究项目(20091104);沈阳市科学技术计划项目(F10-205-1-44)


Atorvastatin Delay the Senescence of Vascular Endothelial Cell Induced by AngiotensinⅡ Through Regulating the Expression of Bcl-2/Bax Protein
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    摘要:

    目的探讨阿托伐他汀对血管紧张素Ⅱ诱导人脐静脉内皮细胞衰老中凋亡调控基因Bcl-2、Bax及Bcl-2/Bax蛋白表达的影响。方法体外培养人脐静脉内皮细胞,用血管紧张素Ⅱ(AngⅡ)及阿托伐他汀干预,分为对照组、血管紧张素Ⅱ诱导组及阿托伐他汀组,采用β-半乳糖苷酶染色和流式细胞术鉴定细胞衰老,并利用免疫细胞化学染色法、Western blot法分析各组凋亡相关基因Bcl-2、Bax蛋白表达水平。结果血管紧张素Ⅱ诱导组存活的细胞数与对照组相比81.90%±0.04%;约80%的细胞呈现β-半乳糖苷酶活性阳性染色和流式细胞仪检测细胞周期停滞于G0/G1,证实细胞衰老;与血管紧张素Ⅱ诱导组相比,阿托伐他汀组Bcl-2蛋白表达水平明显增高(p<0.05),Bax蛋白表达水平降低(p<0.05),Bcl-2/Bax比值显著增加(p<0.05)。结论血管紧张素Ⅱ可诱导体外培养的人脐静脉内皮细胞老化,从而复制细胞衰老。Bcl-2、Bax蛋白表达的失衡可能是血管衰老的重要分子机制之一,阿托伐他汀有一定的延缓血管衰老的作用。

    Abstract:

    AimTo explore the effects of Atorvastatin on the senescence in human umbilical vein endothelial cells (HUVEC) induced by angiotensinⅡ(AngⅡ) and to study its potential molecular mechanism.MethodThe HUVEC were cultured in vitro and divided into 3 groups,the control group,AngⅡgroup (stimulated and intervened by AngⅡ10-6mol/L for 48 h),Atorvastatin group (10-3mol/L Atorvastatin was added to cell 1 h before 10-6mol/L AngⅡ).β-Gal stain and cell cycle analysis were used to identify cell aging status;and the expression of apoptosis-association genes Bcl-2 and Bax were detected by immunocytochemistry,and Western blot.ResultsAngⅡ stimulation enhanced the positive cell number of β-gal stained HUVEC,depressed cell proliferation.The AngⅡ group inhibited the expression of Bcl-2 protein and increased the expression of Bax protein compared with the Atorvastatin group markedly (p<0.05),Bcl-2/Bax was decreased significantly(p<0.05) in the AngⅡgroup.The Atorvastatin group increased the expression of Bcl-2 protein and decreased the expression of Bax protein compared with the AngⅡ group evidently (p<0.05),Bcl-2/Bax was increased significantly(p<0.05) in the Atorvastatin group.ConclusionsAtorvastatin probably delay the senescence of vascular endothelial cell induced by AngⅡ through regulating the expression of Bcl-2/Bax protein.

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单海燕,刘姝,白小涓,陈香美.阿托伐他汀通过调节Bcl-2/Bax蛋白表达延缓血管内皮细胞衰老[J].中国动脉硬化杂志,2012,20(1):11~15.

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  • 收稿日期:2011-06-23
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