大鼠颈动脉球囊损伤后血管平滑肌细胞E1A激活基因阻遏子的表达变化  

The change of cellular repressor of E1A-stimulated genes of vascular smooth muscle cell after balloon injury of rat carotid arteries

作　　者：韩雅玲[1] 王效增[1] 康建[1] 刘海伟[1] 李少华 

机构地区：[1]沈阳军区总医院全军心血管内外科研究所心内科,110016 [2]美国新泽西州Robert Wood Johnson医学院病理实验科

出　　处：《中华心血管病杂志》2004年第1期53-58,共6页Chinese Journal of Cardiology

基　　金：国家自然科学基金资助项目 (3 0 0 70 2 80 )

摘　　要：目的　探讨血管再狭窄发生的病理生理机制及E1A激活基因细胞阻遏子 (CREG)在新生内膜增殖中的调控作用 ,为研究CREG防治增生性血管疾病的作用奠定基础。方法　采用大鼠颈动脉球囊损伤后血管再狭窄的动物模型 ,以免疫组织化学染色、逆转录 聚合酶链反应 (RT PCR)方法 ,检测新生内膜中增殖细胞核抗原 (PCNA)和平滑肌α肌动蛋白 (SMα actin)的表达变化及血管壁中CREGmRNA水平、蛋白表达的动态变化。结果　大鼠颈动脉球囊损伤后 1d血管壁CREGmRNA水平开始下降 ,至损伤后 5d达最低 ,损伤后 7dCREGmRNA表达回升 ,至 2 8d时仍未回到正常对照组的水平。血管损伤后 3d血管内表面可见增殖的血管平滑肌细胞 (VSMC) ,PCNA染色阳性 ,其胞浆内SMα actin和CREG染色均为阴性 ;损伤后 5d新生内膜形成并增厚 ,PCNA阳性细胞数达到高峰 ,部分VSMC胞浆内SMα actin和CREG染色均呈阳性 ;损伤后 2 8d管腔严重狭窄 ,新生内膜中PCNA表达已较低 ,SMα actin和CREG表达均明显增加 ,新生内膜SMα actin表达程度仍弱于中膜 ,CREG表达程度接近中膜。损伤后不同时间点VSMC增殖程度与血管壁中CREGmRNA水平的变化呈负相关 (r =- 0 80 ,P <0 0 5 ) ,CREGmRNA的表达为先降低 ,后回升 ,而细胞增殖指数为先升高 ,后回降。结论　VSMC的表?Objective To explore pathophysiology pathogenesis of vascular restenosis and regulation role of cellular repressor of E1A stimulated genes(CREG) during neointimal proliferation so as to contribute to the prevention and therapy of vascular proliferative diseases by CREG. Methods The model of vascular restenosis established by balloon injury of rat carotid arteries was used. Immunohistochemistry and reverse transcriptase polymerase chain reaction (RT PCR) were used to detect the change of proliferation cell nuclear antigen (PCNA) and smooth muscle α actin (SM α actin) expression of neointimal formation and CREG expression of the arterial wall at different time after balloon injury. Results The expression of CREG mRNA of the arterial wall was decreased on 1st day after balloon injury of rat carotid arteries, reached its lowest value on 5th day after balloon injury, increased gradually from 7th day after balloon injury and was lower compared with that in the control group on 28th day after balloon injury. The proliferation of vascular smooth muscle cell (VSMC) existed on the surface of vascular lumen on 3rd day after balloon injury, the expression of PCNA was positive, the expression of SM α actin and CREG was negative. On 5th day after balloon injury, the neointima was formed and thickened, the expression of PCNA reached its peak value, the expression of SM α actin and CREG was partly positive in the neointimal VSMC. Vascular lumen was seriously narrow on 28th day after balloon injury, the expression of PCNA was significantly decreased and the expression of SM α actin and CREG was significantly increased, the expression of SM α actin in the neointima was lower than that in the media, but the expression of CREG in the neointima was close to that in the media. There were negative relationships between the cell proliferation index and CREG mRNA expression of the arterial wall at different time after injury ( r =-0 80, P <0 05). The expression of CREG mRNA was decreased at beginning and then in

关 键 词：大鼠 颈动脉球囊损伤 血管平滑肌细胞 E1A激活基因阻遏子 表达 血管再狭窄 

分 类 号：R654.3[医药卫生—外科学]