目的 研究注射用重组人尿激酶原(rhPro-UK)对家兔下腔静脉血栓的溶栓作用,观察其出血副作用以及对凝血功能的影响,并对其作用机制进行探讨。方法 家兔采用电刺激伴狭窄法制备下腔静脉血栓模型,5d后耳缘iv25、50、100kU/kgrhPro-UK,输注完毕1h后测定家兔出血时间和出血量;颈动脉取血分离血浆,试剂盒法检测血浆凝血因子活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)以及纤维蛋白原(FG)含量,ELISA试剂盒法检测血浆内纤溶酶原(Plg)水平;取血栓,测定血栓湿质量、干质量以及基质量。结果 家兔静脉注射rhPro-UK后,出血时间有所延长,出血量有所增加,FG和Plg水平均有一定程度的降低,但凝血功能指标APTT、PT和TT均无显著增加。血栓湿质量、干质量及基质量均显著降低,并具有一定的剂量相关性,表明rhPro-UK对下腔静脉血栓有显著的抑制作用。结论 rhPro-UK具有良好的抑制下腔静脉血栓作用,作用机制与其特异性地催化血栓生成部位的纤溶酶原生成纤溶酶有关。

Objective To study thrombolysis of Recombinant Human Prourokinase (rhPro-UK) for injection on inferior vena cava thrombosis in rabbits, observe its bleeding side effect and its effect on coagulation function, and explore its mechanism. Methods Inferior vena cava thrombosis model in rabbits were established by electrical stimulation and stenosis. rhPro-UK of 25, 50, and 100 kU/kg were injected into the ear vein of rabbits after 5 d. Bleeding time and blood loss were measured 1 h after infusion. Blood was taken from the jugular vein and prepared into plasma. Activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), and fibrinogen (FG) were determined by kits, and plasminogen level in plasma was determined by ELISA method. Thrombus was taken out, and wet weight, dry weight, and base quality of thrombus were weighed. Results Bleeding time and blood loss of rabbits were extended, and levels of FG and Plg were reduced slightly, but there was no significant increase in coagulation parameters APTT, PT and TT. Wet weight, dry weight, and base quality of thrombus were all significantly reduced in a dose-dependent manner after iv rhPro-UK, which indicated that rhPro-UK had a significant inhibitory effect on deep vein thrombosis. Conclusion rhPro-UK has a good inhibitory effect of inferior vena cava thrombosis, and its mechanism of action is related to its specific catalytic action of promoting plasminogen in angiogenesis site to generate plasmin.

天津市应用基础与前沿技术研究计划青年项目(14JCQNJC13300)