替罗非班在家兔血栓模型中对血小板聚集的影响

 目的通过替罗非班(tirofiban)对动物血栓模型的干预,观察在动脉粥样硬化(AS)血栓形成过程中替罗非班对血栓成分、血小板聚集率(PAR)和糖蛋白Ⅰb(GPⅠb)的影响。方法20只雄性新西兰白兔,高胆固醇喂养18周,建立AS模型,并随机分为两组:替罗非班组(n=10)和模型组(n=10);另取5只雄性新西兰白兔用普通颗粒饲料喂养作为对照组。第18周末腹腔注射拉塞尔喹蛇毒液(RVV)150μg·kg^-1,0.5 h后行耳缘静脉或耳缘中央静脉留置针注射血管紧张素Ⅱ(ATⅡ)30μg·kg^-1。24 h后重复1次,建立血栓模型。第二次注射时,替罗非班组经电子蠕动泵给予替罗非班注射液0.4μg·kg^-1·min^-1静滴,模型组和对照组给予生理盐水静滴,于注射前和注射后8 h取静脉血,比浊法测定血小板聚集率。处死动物取斑块和血栓部位的动脉壁进行病理组织形态学观察,高倍光镜分析血栓成分差异。取血栓进行GPⅠb免疫组化检测。结果镜下观察替罗非班组血栓成分以红细胞为主,模型组的血栓成分以大量血小板为主;替罗非班组和模型组血小板聚集率明显高于对照组(P<0.05);替罗非班组与模型组相比较,替罗非班静滴后明显降低了血小板聚集率(P<0.05),GPⅠb在替罗非班组血栓中的表达较模型组明显减少。结论GPⅡb/Ⅲa受体拮抗剂替罗非班可明显降低PAR和GPⅠb,减少血栓成分中的血小板数量,为临床上治疗急性冠脉综合征(ACS)提供了理论依据。

Effect of Tirofiban on Platelet Aggregation in Rabbit Thrombosis Model

OBJECTIVE To investigate the intervention of GPⅡb/Ⅲa antagonist tirofiban on platelet aggregation in the rabbit model with atherosclerosis and thrombosis in vivo.METHODS AngiotensinⅡinduced thrombosis models in atherosclerotic rabbits.Twenty-five male New Zealand white rabbits were randomize divided into the treated group(cholesterol-rich diet +RVV+ ATⅡ+tirofiban 0.4 μg·kg^-1·min^-1 continuous venous injection for 24 h),untreated group(cholesterol-rich diet +RVV+ATⅡ+saline venous injection for 24 h) and controlled group(normal diet +RVV +ATⅡ+saline venous injection for 24 h).Platelet aggregation rate was measured by nephelometery.The thrombus was harvested for GPⅠb immunohistochemistry analysis.RESULTS Lots of plaques existed in aortic in both the treated group and the untreated group.Thrombus obtained in the treated group consisted of erythrocyte and fibrin,while thrombus in the untreated group consisted of platelet and fibrin.No thrombus and plaque were found in control group.Compared with untreated group,PAR and GPⅠb decreased in the treated group(P<0.05).CONCLUSION Tirofiban can inhibit platelet aggregation in thrombosis.