肺血栓栓塞症大鼠血浆尿激酶型纤溶酶原激活物及其受体的动态变化及其意义

目的观察大鼠肺血栓栓塞症(PTE)后不同时间血浆尿激酶型纤溶酶原激活物(uPA)和尿激酶型纤溶酶原激活物受体(uPAR)的动态变化,并探讨两者与血栓自溶率的相关性。方法经颈外静脉注入加热125I-标记纤维蛋白原自体血栓,复制大鼠PTE模型,随机分组如下:1)正常对照组;2)PTE组:又分为PTE 4 h组(PTE 4 h)、PTE 24 h组(PTE 24 h)、PTE 3 d组(PTE 3d)、PTE 5 d组(PTE 5 d),即分别在造模成功后观察4 h2、4 h3、d、5 d后处死小鼠,留取血浆标本测定uPA、uPAR的水平;留取左肺观察肺组织病理改变;留取心脏、肺脏、全血以计算血栓自溶率。结果血浆uPA、uPAR水平在PTE后4 h略有上升(P>0.05),PTE后24 h明显增加(P<0.05),3 d时最高(P<0.01),5 d时开始下降,但仍明显高于正常对照组(uPAP<0.05,uPARP<0.01);PTE后4 h组、24 h组、3 d组血浆uPA质量浓度与血栓自溶率正相关(4 hr=0.758,P<0.05;24 hr=0.764,P<0.05;3 dr=0.778,P<0.05),血浆uPAR质量浓度与血栓自溶率正相关(4 hr=0.701,P<0.05;24 hr=0.764,P<0.05;3 dr=0.777,P<0.05)。肺组织病理改变:PTE后4 h有少量继发血栓形成,血栓及血管壁内可见白细胞浸润;PTE后3 d、5 d见注入的血凝块明显溶解,代之以新形成的血栓。结论PTE后血浆uPA、uPAR水平增加,促进内源性纤维蛋白溶解。

Dynamic Changes and Significance of Plasma Urokinase-Type Plasminogen Activator and its Receptor in Rats after Pulmonary Thromboembolism

Objective To observe the dynamic changes of urokinase-type plasminogen activator(uPA) and its receptor(uPAR) in rats after pulmonary thromboembolism(PTE) and their relationship to spontaneous thrombolysis rate.Methods PTE was induced in Male Sprague Dawley(SD) rats through injecting heated()~(125)iodine-labeled fibrinogen autologous thromboembolic into external jugular veins.Thirty-five rats were randomly assigned into following groups(each 7): 1) Healthy control group;2) PTE group including PTE 4 h group,PTE 24 h subgroup,PTE 3 d subgroup,PTE 5 d subgroup.The rats were separately sacrificed at 4 h,24 h,3 d,5 d after the PTE model was successfully made.Plasma samples were extrated and reserved for analysis of urokinase-type plasminogen activator(uPA) and its receptor(uPAR),so were hearts,lungs and whole blood for spontaneous thrombolysis rate.Results 1) Plasma concentrations of uPA and uPAR elevated after PTE(24 h P<0.05;3 d P<0.01;PTE 5 d uPA P<0.05,uPAR P<0.01)and reached a peak valuein PTE 3 d group,then began to decrease in PTE 5 d subgroup.Plasma concentration of uPA was positively correlated with spontaneous thrombolysis rate after PTE in 4 h,24 h,3 d subgroups(4 h r=0.758,P<0.05;24 h r=0.764,P<0.05;3 d r=0.778,P<0.05),so was plasma uPAR(4 h r=0.701,P<0.05;24 h r=0.764,P<0.05;3 d r=0.777,(P<)(0.05)).Histopathological results of the lung: Secondary thrombosis and infiltration of leukocyte in thrombus and vascular wall was observed in PTE 4 h subgroup.The injected clot was obviously dissolved in PTE 3 d and 5 d subgroup replaced by secondary thrombus.Conclusion 1) Plasma levels of endogenous uPA and uPAR are increased at different time points after PTE which promote endogenous fibrinolysis.