目的 研究注射用重組人尿激酶原(rhPro-UK)對家兔下腔靜脈血栓的溶栓作用,觀察其出血副作用以及對凝血功能的影響,并對其作用機制進行探討。方法 家兔采用電刺激伴狹窄法制備下腔靜脈血栓模型,5d后耳緣iv25、50、100kU/kgrhPro-UK,輸注完畢1h后測定家兔出血時間和出血量;頸動脈取血分離血漿,試劑盒法檢測血漿凝血因子活化部分凝血活酶時間(APTT)、凝血酶原時間(PT)、凝血酶時間(TT)以及纖維蛋白原(FG)含量,ELISA試劑盒法檢測血漿內纖溶酶原(Plg)水平;取血栓,測定血栓濕質量、干質量以及基質量。結果 家兔靜脈注射rhPro-UK后,出血時間有所延長,出血量有所增加,FG和Plg水平均有一定程度的降低,但凝血功能指標APTT、PT和TT均無顯著增加。血栓濕質量、干質量及基質量均顯著降低,并具有一定的劑量相關性,表明rhPro-UK對下腔靜脈血栓有顯著的抑制作用。結論 rhPro-UK具有良好的抑制下腔靜脈血栓作用,作用機制與其特異性地催化血栓生成部位的纖溶酶原生成纖溶酶有關。

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.

天津市應用基礎與前沿技術研究計劃青年項目(14JCQNJC13300)