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目的观察重组尿激酶原(recombinant prourokinase,r Pro-UK)治疗大鼠肺血栓栓塞症(pulmonary tromboembolus,PTE)后血浆纤溶因子的变化及其意义。方法雄性SD大鼠28只,颈外静脉注入加热125-碘(125I)标记纤维蛋白原(Fib)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 5 d组,即在造模成功后观察5 d活杀;3 Pro-UK溶栓治疗组:分为多次给药亚组(PTE造模成功后第3天,予Pro-UK 1 mg/kg,后连续2 d给予Pro-UK 0.25 mg/kg,最后1 d给药2 h后与PTE 5 d组大鼠同时活杀)和单次给药亚组(PTE造模成功后第3天给予Pro-UK 1 mg/kg,后连续2 d给予生理盐水,活杀时间同PTE 5 d组大鼠)。每组7只,在实验结束时经颈动脉放血活杀动物,留取血浆标本测定尿激酶型纤溶酶原激活物(u-PA)、尿激酶型纤溶酶原激活物受体(u-PAR)、Fib的水平和α2-抗纤溶酶(α2-AP)的活性。结果 1多次给药亚组血浆u-PA、u-PAR水平较PTE 5 d组(Pu-PA<0.05,Pu-PAR<0.01)及单次给药亚组(Pu-PA<0.01,Pu-PAR<0.05)明显升高,与血栓溶解率正相关(ru-PA=0.766,P<0.05;ru-PAR=0.785,P<0.05)。2 r Pro-UK溶栓治疗后血浆Fib浓度和α2-AP活性与PTE 5 d组比较无显著差异(P>0.05)。结论 1 r Pro-UK溶栓治疗可促进内皮细胞合成和分泌u-PA、u-PAR,有助于血栓溶解,这可能是r Pro-UK的一个重要的溶栓机制。2 r Pro-UK多次给药方案治疗大鼠PTE没有引起继发全身纤溶激活,具有纤维蛋白特异性。
Objective To observe the changes and significance of plasma fibrinolysis after recombinant prourokinase (r Pro-UK) for the treatment of pulmonary thromboembolism (PTE) in rats. Methods Twenty-eight male Sprague-Dawley rats were randomly divided into the following groups: 1 normal control group; 2 PTE 5 d group, 28 male SD rats were injected with 125I-labeled fibrinogen (Fib) That is, after 5 days of successful modeling, the live kill was observed. 3 Pro-UK thrombolytic therapy group was divided into multiple subgroups (Pro-UK 1 mg / kg on the third day after the success of PTE modeling, Pro-UK 0.25 mg / kg on day 2 and live 2 h on day 1 and PTE on day 5) and a single administration subgroup (Pro-UK 1 mg / kg, and then given normal saline for 2 days. The killing time was the same as that in the PTE 5 d group. (N = 7). The animals were sacrificed at the end of the experiment by bloodletting the carotid artery and the plasma samples were collected for determination of urokinase-type plasminogen activator (u-PA), urokinase-type plasminogen activator receptor -PAR), Fib levels and α2-antiplasmin (α2-AP) activity. Results Compared with PTE 5 d group (Pu-PA <0.05, Pu-PAR <0.01) and single-dose subgroup (Pu-PA <0.01, Pu -PAR <0.05), which was positively correlated with thrombolytic rate (ru-PA = 0.766, P <0.05; ru-PAR = 0.785, P <0.05). There was no significant difference in Fib concentration and α2-AP activity between 2 r Pro-UK and PTE 5 d group after thrombolysis (P> 0.05). Conclusions 1 r Pro-UK thrombolytic therapy can promote the synthesis and secretion of u-PA and u-PAR in endothelial cells, which may contribute to thrombolysis, which may be an important thrombolysis mechanism of r Pro-UK. 2 r Pro-UK multiple regimens for the treatment of rat PTE did not cause secondary systemic fibrinolysis, with fibrin specificity.