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

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

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。

Aim To explore the effects of Atorvastatin on the senescence in human umbilical vein endothelial cells （HUVEC） induced by angiotensin Ⅱ（ Ang Ⅱ ） and to study its potential molecular mechanism. Method The HUVEC were cultured in vitro and divided into 3 groups, the control group, Ang H group （ stimulated and intervened by Ang Ⅱ10 -6mol/L for 48 h） ,Atorvastatin group （ 10-3mol/L Atorvastatin was added to cell 1 h before 10-6mol/L Ang Ⅱ ）. β-Gal stain and ceil cycle analysis were used to identify cell aging status;and the expression of apoptosis-asseciation genes Bcl-2 and Bax were detected by immunocytochemistry, and Western blot. Results Ang H stimulation enhanced the positive cell number of β-gal stained HUVEC, depressed cell proliferation. The Ang Ⅱ 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 Ang H group. The Atorvastatin group increased the expression of Bcl- 2 protein and decreased the expression of Bax protein compared with the Ang Ⅱ group evidently （ P 〈 0. 05 ）, Bcl-2/Bax was increased significantly（P 〈 0. 05） in the Atorvastatin group. Conclusions Atorvastatin probably delay the senescence of vascular endothelial cell induced by Ang Ⅱ through regulating the expression of Bcl-2/Bax protein.