大鼠血管平滑肌增殖器官模型的建立及其机制探讨  

Establishing an Organic Model of SMC Proliferation with Cultured Aorta of Rats and Exploring the Underlying Mechanism

作　　者：张艳林[1] 王彩英[1] 杨芹[1] 杨亚安[1] 顾永平[1] 王旻晨[1] 吴开云[1] 

机构地区：[1]苏州大学医学院心血管病研究室,苏州215123

出　　处：《生物医学工程学杂志》2008年第6期1405-1410,共6页Journal of Biomedical Engineering

基　　金：苏州大学创新团队项目资助(9034602);苏州大学医学发展基金资助项目(EE134519)

摘　　要：为更好地研究血管平滑肌细胞增生性疾病的机理及防治,建立一种体外VSMC增殖器官模型,并对其机制作初步探讨。HE染色和免疫组化染色显示,大鼠主动脉段在体外拉伤内皮并经20%血清培养后,会出现中膜VSMCs的增殖。体外培养5 d后血管壁VSMC就出现不同程度增生,其中13 d的血管有明显斑块形成;免疫组织化学染色见有标记的增生VSMCs;RT-PCR检测显示,Hrg-1和SM22αmRNA的表达随培养天数增多而减少,至13 d检测不出。而在同样体外培养10 d情况下,与对照组相比,内皮损伤组培养上清中ET-1明显增多,Hrg-1、SM22a mRNA表达下调,Brdu标记增殖细胞增多,当加入内皮素受体阻断剂BQ123后标记细胞明显减少,其中血清培养组与无血清培养组相比,以上检测变化有显著性差异。结果表明,大鼠主动脉经体外培养能诱导平滑肌细胞异常增生并且表型从收缩型向合成型转化,ET-1和血清作用是该模型平滑肌增殖的主要因素。本模型为研究血管平滑肌增殖性疾病的机理和防治提供了一个较好的实验平台。To study the mechanism of proliferous vascular disease as well as its prevention and treatment, an organic model was established with cultured aortas of rats, and the mechanism there-in invloved was probed. Immunostaining histology showed that smooth muscle celI（SMC） proliferation was observed in the aorta segments of rats, after their endothelia being injured and cultured in vitro with 20% fetal bovine serum. After being cultured for 5 days, various degrees of proliferation of SMC on cultured artery segments were observed by HE staining, and conspicuous plaques were developed after being cultured for 13 days. The prolifemus SMC was also observed by Brdu labeling . RT-PCR examination showed that the mRNA expression of hypertension-related gene-l（Hrg-1） and smooth muscle 22 alpha（SM22α） in the aortas decreased with the prolongation of culture time, and completely disappeared after being cultured for 13 days . But when cul- tured in vitro for ten days, the ET-1 content of supernatant and the pmliferous SMC labeled by Brdu increased obviously and the expressions of Hrg-1 and SM22a decreased after the endothelium was destroyed. Compared with the injured endothelium groups, the proliferous SMC of injured endothelium plus BQ123 groups decreased visibly. The same significant differences between serum groups and serum-free groups were also observed. These results suggest that the culturing of rat aorta segments in vitro can induce the proliferation of SMC and the transform of phenotype from contractile type to synthetic type. The ET-1 and serum are the main factors in the proliferation of SMC and in the transform of phenotype. This organic model could serve as a good experimental platform for the researches into the mechanism of proliferous vascular disease as well as its prevention and treatment.

关 键 词：器官模型 平滑肌增殖 表型 高血压相关基因-1 平滑肌22α 内皮素-1 

分 类 号：R-332[医药卫生]