损伤血管内、外膜致动脉粥样硬化形成及信号转导机制的对比研究  

Vascular intimal and adventitia injuries in atherogenesis and signal transduction mechanism:a comparative study

作　　者：王华[1] 贺治青[1] 刘星[1] 陈玮[1] 周卫健[1] 梁春[1] 吴宗贵[1] 

机构地区：[1]第二军医大学附属长征医院心内科,上海200003

出　　处：《上海医学》2009年第4期293-295,I0002,共4页Shanghai Medical Journal

基　　金：国家重点基础研究发展计划(973计划)资助项目(2005CB523309)

摘　　要：目的对比研究损伤血管内、外膜致动脉粥样硬化形成及信号转导的机制。方法新西兰大白兔高脂喂养两周后,剔除血脂不高者,分别采用胶原酶消化颈动脉内膜和外膜的方法建立相应的血管损伤模型。将造模后的新西兰大白兔随机分为未损伤对照组和内、外膜损伤组。通过苏木精-伊红染色和Western印迹法,观察颈动脉内、外膜损伤对内膜增生和动脉粥样硬化斑块形成,以及P38、细胞外信号调节激酶(ERK)、核因子-κB(NF-κB)信号通路的影响。结果1周时,外膜损伤组内膜/中膜面积比(IMR)为0.38±0.02,显著高于内膜损伤组(0.17±0.01,P<0.05);8周后,内膜损伤组的IMR为0.75±0.05,反而显著高于外膜损伤组(0.64±0.03,P<0.05)。血管损伤造膜8周后,内、外膜损伤组血管组织中P38、NF-κB的蛋白表达均显著高于未损伤对照组(P值均<0.05),仅内膜损伤组ERK1的表达显著高于未损伤对照组(P<0.05)。结论血管内、外膜损伤诱导的动脉粥样硬化斑块形成,除激活共同的P38以及NF-κB信号通路外,对ERK1/2表达的影响不同。Objective To investigate the different roles of vascular intimal and adventitial injuries in atherosclerosis and the related signal transduction pathways in rabbits. Methods New Zealand rabbits were fed with high cholesterol diet for two weeks and those without high blood lipid were excluded. Adventitial and intimal injury models were created by digesting rabbit carotid arteries with collagenase. The animals were then divided into non-injury control group, intimal injury group, and adventitial group. Immunochemistry was used to evaluate the difference of atherosclerosis induced by vascular intimal and adventitial injuries, and Western blotting was used to explore the protein expression of P38, ERK1/2 and nuclear factor （NF）-κB in vascular tissues. Results One week later the intimal-to-medial area ratio （IMR） in the adventitial injury group was 0.38± 0.02, which was significantly higher than that of the intimal injury group （0.17± 0.01, P〈0.05）. Eight weeks later, the IMR in the adventitial injury group was 0.64 ± 0.03, which was significantly lower than that of the intimal injury group （0.75± 0.05, P〈0. 05） meanwhile, the expression of P38 and NF-KB protein in the two injury groups was significantly higher than that of the non-injury control group （all P〈0. 05）. The ERK1 expression was markedly higher in the intimal injury group compared with the non-injury group （P〈0.05）. Conclusion Both of vascular intimal and adventitial injuries can induce atherosclerosis and activate P38 and MAPK-NF-κB pathway, but they have no effect on ERK1/2 expression.

关 键 词：动脉粥样硬化 血管外膜 内膜 丝裂原激活的蛋白激酶 核因子-ΚB 

分 类 号：R543.5[医药卫生—心血管疾病] R392.12[医药卫生—内科学]