雌二醇对大鼠血管平滑肌细胞细胞周期和周期相关蛋白的影响

Effects of estradiol on cell cycle and cyclin proteins of vascular smooth muscle cells in rats

目的研究17β雌二醇(E2)对大鼠血管平滑肌细胞(VSMC)生长的影响。方法应用流式细胞仪检测不同浓度E2在有或无血清刺激下对传代VSMC细胞周期及其相关蛋白Cy-clinD1和CDK4表达的影响。结果在有血清的条件下,E2(1、10、100nmol/L)促进VSMC从G1期向S过渡,其S期细胞比率分别为(31.89±9.14)%、(35.90±4.59)%、(30.77±1.20)%,显著高于对照细胞(21.63±1.80)%(P<0.05),并伴随CyclinD1和CDK4蛋白表达量的显著增高;而在无血清的环境中,高浓度(10、100nmol/L)E2则抑制VSMC增殖,其S期细胞比率分别为(9.93±1.43)%、(8.76±1.80)%,显著低于对照细胞(16.58±3.04)%(P<0.05),且伴随Cy-clinD1和CDK4蛋白表达量降低。结论E2在有或无血清条件下分别对VSMC增殖起促进或阻滞作用,其机制可能是通过影响CyclinD1和CDK4蛋白的表达而作用于VSMCG1期。

Objective To study the effects of 17β-estradiol (E2) on the growth of cultured rat vascular smooth muscle cells (VSMC).Methods The cell cycle and the expressions of Cyclin D1 and CDK4 proteins were examined by flow cytometry in VSMC cultured in different concentrations (0-100 nmol/L) of 17β-estradiol with or without serum.Results Under serum-stimulating conditions,17β-estradiol (1,10,100 nmol/L) promoted VSMC proliferation by accelerating their cell cycle progression from G1 to S phases,and the cell rates at S were (31.89±9.14)%,(35.90±4.59)% and (30.77± 1.20)% respectively,significantly higher than the corresponding values of control cells (21.63± 1.80)%. This was accompanied by the significantly increased expression of Cyclin D1 and CDK4 proteins.In the cultures without serum,however,high concentrations (10,100 nmol/L) of E2 induced a cell cycle arrest at G_1 phase,which was characterized by decreased cell rates at S phase [(9.93±1.43)% and (8.76%±1.80)% respectively, P< 0.05] as compared with the corresponding control values and a down-regulation of expressions of Cyclin D1 and CDK4 proteins.Conclusion E2 can either promote or inhibit VSMC proliferation depending upon the presence or absence of serum mitogens.The underlying mechanism may be associated with the hormone's action on the expression of Cyclin D1 and CDK4 that act as the G_1 phase regulators.