阿司匹林局部干预防治移植静脉血栓和新生内膜增生

目的 将阿司匹林局部用于大鼠移植血管周围,观察不同时间静脉移植血管血栓及新生内膜增生情况,并分析NO与ET-1等因子的变化及其意义.方法 采用SD大鼠颈静脉分支-颈动脉间置模型,于移植后不同时间获取移植血管进行组织学和α-SM-actin及CD-34免疫组化分析.同时获取血液标本对NO及ET-1进行测定.实验分4组,分别为对照组、局部用药组、口服用药组和联合用药组.结果 术后7 d HE染色,联合用药组血栓面积小于对照组(P<0.05);术后14 d,对照组新生内膜厚度大于局部用药组及联合用药组(P<0.05).α-SM-actin免疫组化显示术后7 d对照组和口服用药组α-SM-actin+细胞增生较为明显,并向新生内膜迁移,而局部用药组和联合用药组其增殖及迁移情况较轻.CD34免疫组化显示术后7 d局部和联合用药组血管内膜CD34+细胞较其余两组明显.术后7 d治疗各组ET-1水平均低于对照组(P<0.05);术后14 d治疗各组NO水平升高(P<0.05).结论 阿司匹林局部应用或局部口服联合应用可能通过增加NO及降低ET-1发挥对内皮细胞的保护作用与对移植静脉血栓形成的抑制作用,并可能抑制平滑肌样细胞增殖,从而减轻新生内膜增生.

Locally applied aspirin inhibits vein grafts thrombosis and neointima formation

Objective To investigate the anti-thrombosis and neointimal hyperplasia effect of local aspirin apply, and analysis the level changes of plasma NO and ET-1. Methods SD rat jugular vein-carotid ＇artery interposition model was selected with different treatment protocols. All rats were divided into control group, topical group, oral group and combined treatment group. Specimens were harvested at different time postoperatively to investigate the severity of thrombus and neointimal hyperplasia , o~-SM-actin and CD-34 immunohistochemical analysis also studied. At the same time, the level changes of plasma NO and ET -1 were also measured using oxidation -reduction or ELISA. Results On the seventh day after surgery, vascular thrombosis area in control group was greater than that of the combined treatment group （P 〈0. 05）. On the fourteenth day ＂after surgery, the neointimal hyperplasia in control group was severe compared with that of the local and combined treatment groups （ P 〈 0. 05 ）. Seven days after surgery, α-SM-actin immunohistochemistry showed that α-SM-actin cell proliferation and migration was more obvious in control and oral groups, while the changes were less in the local and combined treatment groups . CD-34 immunohistochemistry showed that intima CD-34＋ cells integrity was well preserved in local and combined treatment groups compared with the other two groups. Post-surgery, ET-1 levels in the control group was significantly higher than that of the other groups （ P 〈 0. 05 ）, while the NO levels decreased （ P 〈 0. 05 ）. Conclusions Topical or combination application of aspirin may not only play a part in protecting endothelial cell , but also inhabiting vein graft thrombosis, and perhaps inhabiting smooth muscle cell proliferation by increasing NO and reducing ET-1.