氯沙坦对动脉粥样硬化斑块内平滑肌细胞凋亡的调控机制研究

目的:研究血管紧张素Ⅱ1型受体阻断剂氯沙坦对动脉粥样斑块内血管平滑肌细胞(vascu-larsmoothmusclecell,VSMC)凋亡的影响及调控机制,阐明氯沙坦抗动脉粥样硬化的作用机理。方法:将21只新西兰大白兔随机分为对照组、高胆固醇组和氯沙坦组。用流式细胞仪检测动脉壁粥样斑块内VSMC增殖周期和凋亡,用透射电镜观察斑块内VSMC超微结构的变化,采用免疫组化染色法检测c-myc蛋白表达水平,采用反转录多聚酶链反应(RT-PCR)方法检测caspases-3mRNA水平。结果:氯沙坦对血脂代谢无影响,氯沙坦组与高胆固醇组比较,主动脉粥样斑块面积比和胆固醇含量减少(P<0.05),粥样斑块中VSMC凋亡增加(P<0.01),c-myc蛋白表达低于高胆固醇组(P<0.05),caspases-3mRNA水平降低(P<0.05)。结论:氯沙坦可能通过对c-myc蛋白和caspase-3基因的调控而促进动脉斑块内过度增殖的VSMC凋亡,从而抑制粥样斑块的形成。

Effect of losartan on the apoptosis of vascular smooth muscle cells in the atherosclerotic plaques in rabbits

Objective:To study the effect of losartan on apoptosis of vascular smooth muscle cells(VSMCs)in the atherosclerotic plaque in rabbits and the antiatherosclerotic effect of losartan.Methods:Twenty one New Zealand rabbits were divided into3groups:control group,high cholesterol group and losartan group.The cell cycles and apoptosis of VSMC were determined by cytometry tech-nique,ultra-structures of VSMCs were observed by electronic microscopy,expression of c-myc protein was detected by immunohistochemistry,and the level of caspases-3mRNA was examined by RT-PCR.Results:A significantly smaller plaque area ratio(P<0.05)was observed in losartan group compaired with high cholesterol group (P<0.05),apoptosis of VSMCs was significantly increased in the losartan group(P<0.01),and there was a higher expression of c-myc protein and lower level of caspases-3in the losartan group(P<0.05).Conclu sion:Losartan could increase the apoptosis of VSMCs in plaque by regu-lating the expression of c-myc protein and caspases-3gene,and so could inhibit the formation of atherosclerotic plaque.