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①目的探讨全反式维甲酸(ATRA)对球囊剥脱大鼠胸主动脉内皮后血管平滑肌细胞(VSMC)表型变化及增殖的影响。②方法雄性SD大鼠54只,随机分为3组。ATRA治疗组(n=24)行球囊剥脱大鼠胸主动脉内皮术,术前4d开始予ATRA芝麻油混悬液(30mg.kg-1.d-1)灌胃至术后处死;手术组(n=24)行球囊剥脱大鼠胸主动脉内皮术,术前4d开始予芝麻油(1mL.kg-1.d-1)灌胃至术后处死;对照组(n=6)除不插入球囊导管外,其他操作同手术组。分别于术后2、7、14、28d取胸主动脉应用苏木精-伊红染色、免疫组化和计算机图像分析法进行形态学、平滑肌α肌动蛋白(SM--αactin)和增殖细胞核抗原(PCNA)表达水平检测。③结果正常动脉VSMC高表达SM--αactin,处于非增殖状态;损伤后中膜SM--αactin表达迅速下降,2d达最低水平,而增殖旺盛,后趋向正常水平;新生内膜在术后7d出现,处于高度增殖状态,SM--αactin含量少,术后14、28d的SM--αactin表达明显增多,而增殖下降。ATRA治疗能明显抑制中膜SM--αactin的下调,诱导内膜和中膜SM--αactin表达,显著抑制VSMC的迁移和增殖,明显抑制新生内膜形成和管腔缩窄。SM--αactin表达与PCNA表达呈显著负相关(r=-0.738,P<0.01)。④结论维持并诱导VSMC于较高的分化状态,抑制VSMC迁移和增殖,是ATRA抑制球囊损伤大鼠主动脉后新生内膜增生和管腔狭窄的可能机制之一。
Objective To investigate the effect of all-trans retinoic acid (ATRA) on the phenotype and proliferation of vascular smooth muscle cells (VSMCs) in the aorta of balloon-evacuated rats. Methods 54 male SD rats were randomly divided into three groups. ATRA treatment group (n = 24) underwent balloon-stripped thoracic aorta endothelia. ATRA sesame oil suspension (30mg.kg-1.d-1) (n = 24) underwent balloon-stripped thoracic aortic endothelium. Sesame oil (1 mL.kg-1.d-1) Insert the balloon catheter, other operations with the surgery group. The thoracic aorta was taken at 2, 7, 14 and 28 days after operation. The morphology, smooth muscle actinine (α - actin) and proliferating cell nuclear were detected by hematoxylin - eosin staining, immunohistochemistry and computer image analysis. Antigen (PCNA) expression level detection. Results The expression of SM - αactin in normal artery VSMC was highly nonsproliferative. The expression of SM - αactin in the mesangial membrane rapidly decreased after 2 days, reached the lowest level on the 2nd day, and proliferated vigorously and then returned to the normal level. The neointimal hyperplasia was found on the 7th day Appeared in a highly proliferative state, the content of SM - αactin was small, the expression of SM - αactin increased obviously and the proliferation decreased after 14 and 28 days. ATRA treatment could significantly inhibit the down - regulation of SM - αactin, induce the expression of SM - αactin in intima and media, significantly inhibit the migration and proliferation of VSMC, and significantly inhibit neointimal formation and lumen narrowing. There was a significant negative correlation between SM - αactin expression and PCNA expression (r = -0.738, P <0.01). ④Conclusion Maintaining and inducing VSMCs to differentiate into higher states and inhibiting the migration and proliferation of VSMCs is one of the possible mechanisms by which ATRA can inhibit neointimal hyperplasia and stenosis after aorta injury in balloon-injured rats.