白介素-1β诱导小型猪冠状动脉内膜增殖时Rho激酶表达与雷帕霉素干预的研究  

Effects of rapamycin on Rho-kinase and p27 mRNA expressions in a porcine coronary intimal proliferation model induced by interleukin-1β

作　　者：苗志林[1] 曾定尹[1] 孙喜琢[2] 周旭晨[1] 程颖[1] 关启刚[1] 张利[2] 何学志[2] 韩凤桐[2] 

机构地区：[1]中国医科大学附属第一医院循环内科 [2]大连市中心医院

出　　处：《中华心血管病杂志》2006年第5期445-449,共5页Chinese Journal of Cardiology

基　　金：国家973计划课题子课题资助项目(2005CB523310)

摘　　要：目的通过小型猪模型观察白介素-1β(IL-1β)诱导冠状动脉内膜增殖时Rho激酶和p27mRNA表达的变化及雷帕霉素干预的作用,探讨Rho激酶表达对冠状动脉狭窄的作用及可能机制。方法通过开胸手术分离小型猪冠状动脉左前降支(LAD)及回旋支(LCX)近端,包裹IL-1β。2周后行冠状动脉造影,然后取标本做病理学检查,并用RT-PCR法测血管壁组织Rho激酶和p27mRNA表达。结果正常冠状动脉血管壁可见Rho激酶mRNA表达及较高水平的p27mRNA表达;用一定量IL-1β诱导冠状动脉内膜增殖,可迅速造成血管管腔狭窄。在此过程中Rho激酶mRNA表达增加3倍以上(30.80±4.10对128.20±15.89),而p27mRNA的表达则明显减弱。雷帕霉素抑制小型猪血管内膜增殖,减少炎细胞浸润,还能减少Rho激酶mRNA表达,并增强p27mRNA的表达。结论Rho激酶在炎症因子诱导的冠状动脉狭窄过程中表达明显增强,通过向下调节p27的活性调控血管内膜的增殖。雷帕霉素通过增强p27mRNA的表达,而减弱Rho激酶对p27的调节,这可能是雷帕霉素抑制血管内膜增殖的新机制。Objective To observe the effects of rapamycin on the expressions of Rho-kinase and p27 mRNA during vascular intimal proliferation in a porcine model of coronary stenosis induced by interleukin-1 β（ IL-1 β）. Methods The proximal segments of LAD and LCX were wrapped with cotton mesh that had absorbed sepharose bead solution with or without IL-1β. Selective coronary angiography was performed two weeks later and the animals were killed for collecting the samples for histopathology and RT- PCR analyzing of Rho-kinase and p27 mRNA. Results The expressions of Rho-kinase and p27 mRNA could be visualized in normal coronary wall. The expression of Rho-kinase mRNA was significantly enhanced and the expression of p27 mRNA was significantly decreased during the process of intimal proliferation induced by IL-1 β. Rapamycin significantly inhibited the intimal proliferation, reduced the infiltration of inflammatory ceils, reduced the expression of Rho-kinase mRNA and increased the expression of p27 mRNA. Conclusions The expression of Rho-kinase mRNA is upregnlated and p27 mRNA downregnlated in coronary artery stenosis induced by IL-1 β and these effects could be abolished by cotreatment with rapamycin.

关 键 词：白细胞介素-1 RHO激酶 雷帕霉素 血管内膜 猪 

分 类 号：R543.3[医药卫生—心血管疾病]