辛伐他汀抑制血管平滑肌细胞增殖的可能表遗传新机制  

New probable epigenetic mechanism of simvastatin action of supressing VSMC proliferation

作　　者：谢静[1] 李晓琼[1] 王树人[2] 李丽娟[3] 

机构地区：[1]四川省第四人民医院病理科,四川成都610016 [2]四川大学华西医学中心病理生理学教研室,四川成都610041 [3]贵州省遵义医学院病理生理教研室,贵州遵义563003

出　　处：《四川生理科学杂志》2010年第2期60-63,共4页Sichuan Journal of Physiological Sciences

摘　　要：目的:探讨降脂药辛伐他汀对血管平滑肌细胞多梳基因Bmi-1的表达及其对细胞增殖、凋亡和细胞周期的影响,以了解辛伐他汀除调脂作用外的抗动脉粥样硬化的可能表遗传新机制。方法:逆转录聚合酶链反应检测不同浓度的辛伐他汀作用于第四代血管平滑肌细胞12、24、36h后Bmi-1 mRNA的表达。倒置显微镜下观察对照组及各组药物作用后细胞数量和形态的变化。四甲基偶氮唑盐法分析各组药物作用后细胞增殖活力的改变。流式细胞术检测细胞周期和细胞凋亡。结果:经5～40μmol.L-1辛伐他汀作用于第四代平滑肌细胞12、24和36 h后,Bmi-1mRNA的表达量随药物浓度的增加和时间的延长而呈下降趋势。各浓度辛伐他汀干预组细胞随药物作用时间及浓度的增大均出现了生长抑制。经辛伐他汀处理后各组出现细胞周期G0/G1期阻滞及细胞凋亡,且随药物浓度的升高而增大。结论:辛伐他汀对血管平滑肌细胞表遗传调控基因Bmi-1的抑制,可能是其抗动脉粥样硬化的又一新机制。Objective： To investigate the expression of polycomb gene Bmi-1 in cultured vascular smooth muscle cell （VSMC） in vitro treated by simvastatin with different concentration and different times and the VSMC proliferation, apoptosis and cell cycle, so as to illustrate the potential anti-atherosclerotic mechanism of simvastatin in the level of epigenetics. Methods： The zBmi-1 mRNA transcription in the simvastatin-treated VSMC for 12,24 and 36h were measured by RT-PCR. The morphological changes and the proliferation rate of VSMC were examined by invertmicroscope and methyl tbiazolyl tetrazolium （MTT） assay. The apoptosis and cell cycle were analyzed by flow cytometry. Results： The treatment of VSMC by sirnvastatin induced down-expression of Bmi-1 in a dosedependent and time-dependent manner. The morphological examination and MTT assay in simvastatin-treated groups also disclosed significant inhibition in proliferation rate of VSMC. The analysis of flow cytometry revealed increased apoptosis rate and G0/G1 phase blockage in cell cycle of VSMC in a simvastatin dose-dependent and time-dependent manner. Conclusion：The epigenetic effect of Simvastatin on VSMC could be involved in its anti-atherosclerosis mechanism besides its lipid-lowering role.

关 键 词：辛伐他汀 血管平滑肌细胞 细胞增殖 BMI-1 

分 类 号：R96[医药卫生—药理学]