目的探讨大剂量阿司匹林在移植动脉血管病(TA)发展中的保护作用及其机制。方法建立Brown-Norway(BN)至Lewis大鼠、Lewis至Lewis大鼠的颈总动脉移植模型,受体随机分为阿司匹林组(n=7,术后给予阿司匹林80mg.kg-1.d-1)、空白对照组(n=7,不给予阿司匹林)和同系对照组(n=6,供受体均为Lewis大鼠,不给予阿司匹林)。术后8周取移植动脉行病理组织学检查,利用图像分析系统计算内膜厚度,并采用免疫组织化学方法检测移植动脉壁环氧化酶2(COX-2)和血小板衍生生长因子B链(PDGF-B)的表达。结果同系对照组、阿司匹林组、空白对照组新生内膜厚度分别为3.86±0.61、37.99±9.99、73.10±11.56μm,三组间两两比较差异均有统计学意义(P<0.05),且空白对照组移植动脉新生内膜见丰富的新生毛细血管形成。免疫组化检测显示,COX-2、PDGF-B在同系对照组几乎不表达,在空白对照组高表达,而在阿司匹林组的表达较空白对照组明显下调,阳性细胞数显著减少(P<0.05)。结论大剂量阿司匹林可减轻大鼠TA病情,其机制可能与COX-2、PDGF-B表达下调有关。
Objective To investigate the protective effects of high-dose aspirin on angiopathy of artery transplant and its underlying mechanisms.Methods The common carotid artery transplantation models of Brown-Norway to Lewis and Lewis to Lewis rats were reproduced,and the recipients were randomly divided into three groups: Aspirin group [Brown-Norway to Lewis,aspirin administered in a dose of 80mg/(kg·d),n=7],control group(Brown-Norway to Lewis,received no special treatment,n=7),and isografts group(Lewis to Lewis,received no special treatment,n=6).Eight weeks after transplantation,the transplanted arteries were harvested to observe the histopathological changes,and the intima thickness was estimated using a computer image analysis system.The expression of cyclooxygenase-2(COX-2) and platelet-derived growth factor B(PDGF-B) in the transplanted carotid artery wall was determined by immunohistochemistry method.Results The neointima thickness was significantly lower in isografts group(3.86±0.61μm) than in aspirin group(37.99±9.99μm) and control group(73.10±11.56μm),and in aspirin group it was significantly lower than that in control group(P0.05).Abundant neocapillaries were observed in neointima of vessel transplant in control group.Immunohistochemical analysis showed that PDGF-B and COX-2 were almost negatively expressed in isograft group,but highly expressed in control group,while the expression in aspirin group was lower than that in control group and the count of positive cells decreased significantly(P0.05).Conclusion High-dose aspirin could attenuate artery angiopathy of transplanted common carotid artery in rats,the mechanism may be related with down-regulation of expression of COX-2 and PDGF-B.