雌激素促进合成型大鼠血管平滑肌细胞增殖并诱导细胞周期特异性凋亡  

Estrogen induces proliferation and cell cycle specific apoptosis of synthetic vascular smooth muscle cells

作　　者：阳朝晖[1] 宋健[1] 程蓓[1] 程邦昌[2] 陈锡昌[1] 

机构地区：[1]武汉大学医学院人体解剖与组织胚胎学系,430071 [2]武汉大学人民医院胸心外科

出　　处：《中华实验外科杂志》2005年第3期328-330,i010,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目(30470906)

摘　　要：目的研究17β雌二醇(E2)对大鼠血管平滑肌细胞(VSMC)增殖与凋亡的影响及其可能机制。方法应用流式细胞术检测不同浓度E2(0～100nmol/L)对传代VSMC增殖周期、细胞凋亡及其相关蛋白CyclinD1、bcl2和bax表达的影响;并采用荧光组化技术和共聚焦激光扫描荧光显微镜术对bax的分布进行定位。结果E2(1～100nmol/L)促进VSMC从G1期向S过渡(G0/G1期比率显著低于对照细胞,而S期比率显著高于对照细胞,P<0.05),并伴随CyclinD1蛋白的表达显著增高;与此同时,当浓度达到10nmol/L以上时,E2以时间和剂量依赖的方式导致G2/M期VSMC的凋亡率增高,并伴随bax蛋白表达及bax/bcl2比值上升。结论E2对合成型VSMC具有双重效应,即通过影响CyclinD1表达加速G1～S期转换,从而促进VSMC增殖;同时通过上调bax蛋白的表达选择性地诱导G2/M期细胞凋亡。Objective To investigate the effect of 17β-estradiol (E_2) on proliferation and apoptosis of vascular smooth muscle cells (VSMC) and the possible underlying mechanisms.Methods The progression of cell cycle,the apoptosis and the expressions of CyclinD1,bcl-2 and bax proteins were examined by flow cytometry in subcultured rat VSMC exposed to different concentrations (0-100 nmol/L) of 17β-estradiol.The intracellular localization of bax in VSMC was detected by using immunofluorescent cytochemistry and confocal laser scanning fluorescence microscopy.Results 17β-estradiol (1-100 nmol/L) promoted VSMC proliferation by accelerating their cell cycle progression from G1 to S phases (the rates of the VSMC at S phase were significantly increased,while those at G0/G1 decreased).This was accompanied by an up-regulation of CyclinD1 expression.At the same time,E_2 selectively increased the rate of apoptosis of the cells at G2/M phases in a time-and dose-dependant manner,which was accompanied by a significant raise of bax expression and the ratio of bax/bcl-2.The bax was located in the cytoplasm.Conclusion The effects of E_2 on subcultured (synthetic) VSMC are multiple:it promotes VSMC proliferation by enhancing the expression of CyclinD1 that accelerates G1 to S phase transition,and on the other hand,it induces apoptosis of the cells at G2/M phase by up-regulating the expression of bax.

关 键 词：VSMC 表达 凋亡 大鼠 血管平滑肌细胞增殖 诱导 BAX蛋白 细胞周期 特异性 荧光显微镜 

分 类 号：R543[医药卫生—心血管疾病]