摘要
目的通过VCAM一1siRNA（小分子干扰RNA）抑制血管细胞黏附分子（VCAM-1）的表达，观察对大鼠颈动脉内膜切除术（CEA）后再狭窄的影响。方法构建VCAM-1特异性的siRNA并与慢病毒载体连接；在体外培养的大鼠血管内皮细胞中，应用蛋白印迹的方法验证VCAM-1 siRNA抑制VCAM-1表达的有效性；大鼠颈动脉内膜切除后局部给予VCAM-1siRNA，通过蛋白印迹方法观察VCAM-1表达量变化，应用超声检测和形态学测定，分析术后再狭窄程度的变化。结果VCAM-1 siRNA可以降低VCAM-1蛋白在血管内皮细胞及颈动脉组织中的表达量（P〈0．05）；VCAM．1siRNA可减轻再狭窄程度，增加术后管腔内径和局部血流速度，与对照siRNA相比差异有统计学意义（P〈0．05）；形态学测定分析血管内膜与中膜面积比（I／M），假手术、内膜切除（CEA）组分别为0．35±0．13、3．99±0．65。CEA后再狭窄明显，与假手术组间的差异有统计学意义（P〈0．05）；CEA联合对照siRNA及CEA联合VCAM-1 siRNA的I／M值分别为4．33±0．59、1．79±0．43，VCAM-1 siRNA可以明显减轻再狭窄的程度，两组间的差异有统计学意义（P〈0．05）。结论VCAM．1参与颈动脉内膜切除术后再狭窄的发生，通过VCAM-1 siRNA抑制VCAM-1的表达可以防治再狭窄。
Objective To evaluate the inhibitory effects of VCAM-1 siRNA on VCAM-1 protein expression and restenosis following carotid endartereetomy in rats. Methods Lentivirus-based VCAM-1 siRNA was constructed and its efficacy of blocking VCAM-1 protein expression in endothelial cells and carotids was identified by Western blot. Doppler uhrasonography and morphometrie analysis were performed to measure the degree of restenosis. Results VCAM-1 siRNA decreased the protein expression of VCAM-1 in cultured endothelial cells and carotids. Treatment of VCAM-1 siRNA showed a significant reduction in the restenosis and manifested as an increased blood velocity and linear diameter as compared with control siRNA （ P 〈0.05 ） . Morphometric analysis showed that the ratio of intima to media area （ I/M ） increased significantly in CEA group （ 3.99±0. 65 ） versus sham-operated group （ 0. 35±. 13 ） （ P 〈 0. 05 ）. Furthermore, VCAM-1 siRNA resulted in an evident decrease in the neointimal area （1.79±0. 43 ） as compared with that of the eontrol siRNA （4. 33±0. 59 ） （ P 〈 0. 05 ）. Conclusion VCAM-1 plays an important role in pathogenesis of restenosis after carotid endarterectomy. VCAM-1 siRNA blocks VCAM-1 protein expression and alleviates the restenosis following carotid endarterectomy in rats.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2009年第25期1783-1786,共4页
National Medical Journal of China
基金
国家自然科学基金（30571902）
