缬沙坦对人脐静脉平滑肌细胞凋亡的影响

Effects of valsartan for apoptosis of human umbilical vascular smooth muscle cells

目的:研究血管紧张素受体阻滞剂缬沙坦对人脐静脉血管平滑肌细胞(VSMC)凋亡的调节作用,以探讨缬沙坦抗动脉粥样硬化的作用机制。方法:荧光显微镜观察缬沙坦作用后VSMC凋亡的形态学变化,用流式细胞仪测定缬沙坦用药前后VSMC凋亡率并作周期分析,用流式细胞仪检测缬沙坦对凋亡相关基因Bax,Bcl-2和caspase3表达的影响。结果:缬沙坦高浓度+血管紧张素Ⅱ(AngⅡ)组的VSMC凋亡率较AngⅡ模型组明显提高,缬沙坦单药高、中、低浓度组的VSMC凋亡率较对照组明显提高。细胞周期分析表明,AngⅡ+缬沙坦组与AngⅡ组比较,G0/G1期百分率显著升高,S期百分率显著降低,且具有浓度依赖性。Bax和caspase 3基因经高浓度缬沙坦组作用24 h后表达水平增加,Bcl-2则没有改变。结论:缬沙坦对AngⅡ诱导VSMC的增殖有抑制作用;缬沙坦可能促进VSMC凋亡;缬沙坦促进VSMC凋亡可能与Bax和caspase基因表达增加有关。

Objective ： To investigate the modulation and mechanism of valsartan on the apoptosis of the vascular smooth muscles cells （VSMC）. Methods： Following after the incubation of angiotensin Ⅱ （Ang Ⅱ） and/or valsartan with human umbilical VSMC, respectively, for 24 h, the apoptosis rate of VSMC and the expression of Bax, Bcl-2, caspase 3 were measured using Flow Cytometry （FCM）. The morphologic features of VSMC apoptosis were assessed using fluorescent microscope. Results： Combination of valsartan and Ang Ⅱ showed signi growth cycle ficant increase of the VSMC apoptosis rate, compared to Ang Ⅱ alone. The analysis of the cell disclosed that the combination of Ang Ⅱ and valsartan significantly increased G0/G1 phase rate and decreased S phase in a dose-dependent manner, compared with Ang Ⅱ alone （P 〈 0.05 ）. Significant increments of the Bax and caspase 3 expressions post the incubation with higher concentration of valsartan were observed. No statistical difference in the Bcl-2 expression was found. Conclusion： Valsartan antagonized the VSMC proliferation induced by Ang Ⅱ ; Increment of the VSMC apoptosis by valsartan might be associated with the higher expression of the Bax and caspase 3.