摘要
目的观察在不同时间窗重组尿激酶型纤溶酶原激活物(ru-PA)的溶栓效果,并与重组组织型纤溶酶原激活物(rt-PA)的溶栓效果比较。方法通过颈外静脉注入125I标记人纤维蛋白原的大鼠加热血凝块,建立不同时间大鼠的肺血栓栓塞症(PTE)模型。按随机原则将60只大鼠分成三组:①对照组:再分为PTE2h对照组和PTE3d对照组;②PTE2h溶栓组:再分为ru-PA2h组和rt-PA2h组;③PTE3d溶栓组:再分为ru-PA3d组和rt-PA3d组。PTE2h对照组及溶栓组于处理后2h处死大鼠,PTE3d对照组及溶栓组于处理后48h处死大鼠,留取血标本检测血浆纤维蛋白原(FIB)及α2-抗纤溶酶(α2-AP)水平。取血、肺脏及心脏,测量每分钟γ放射性(cpm)。结果(1)rt-PA2h组的溶栓率明显高于ru-PA2h组,ru-PA2h组又明显高于PTE2h对照组(P均=0.000);其血浆FIB、α2-AP水平明显低于ru-PA2h组(P=0.002,P=0.001)及PTE2h对照组(P=0.003,P=0.002),后两组比较差异无统计学意义(P=0.811及0.700)。(2)ru-PA3d组的溶栓率明显高于rt-PA3d组,rt-PA3d组又明显高于PTE3d对照组(P均=0.000);三组间血浆FIB及α2-AP水平比较,差异无统计学意义(P=0.655,P=0.751)。结论(1)ru-PA1mg/kg溶栓对全身纤溶系统无明显影响,而rt-PA1mg/kg溶栓早期影响全身纤溶系统;(2)体内血栓存在的时间影响ru-PA的溶栓效果,ru-PA对新鲜血栓栓塞的即刻溶栓作用不及rt-PA,但对较陈旧血栓栓塞的溶栓效果强于rt-PA。
Objective To observe the thrombolytic effects of recombinant urokinase-type plasminogen activator （ru-PA） compared with recombinant tissue-type plasminogen activator （rt-PA） on experimental pulmonary embolism in rats. Methods ^125Ⅰ-labeled human fibrinogen heated blood clots were prepared in vitro and injected into the external jugular vein to establish rat models of pulmonary thromboembolism （PTE）. 60 male SD rats were assigned randomly into 3 groups： （ 1 ） the PTE control groups received no thrombolytic treatment （subdivided into the PIE 2 h group and the PTE 3 d group, injected by normal saline respectively at PTE 2 h and 3 d）. （2）The PTE 2 h groups received thrombolytic treatment （subdivided into the ru-PA group and the rt-PA group received bolus injection of ru-PA and rt-PA respectively）. （3）The PTE 3 d groups received thrombolytic treatment （subdivided into the ru-PA group and the rt-PA group）. The above groups of 2 h were sacrificed at 2 h, and the groups of 3 d were sacrificed at 48 h after injection for assay of plasma fibrinogen （FIB） and α2-antplasminand （α2-AP） levels. Meanwhile, the rate of clot lysis was compared between these groups. Results （1）In PTE 2 h groups received thrombolytic treatment, the rate of clot lysis in rt-PA group was higher than that in ru-PA group （ P = 0.000）, and the plasma FIB and α2-AP levels were decreased significantly as compared with ru-PA group （ P = 0.002, P = 0.001 ） and baseline value （ P = 0.003, P = 0.002）. Plasma FIB and α2-AP levels were not different significantly from baseline values after injecting ru-PA（ P = 0.811, P = 0. 700）. （ 2）The rate of clot lysis of ru-PA 3 d group was higher than that of rt-PA 3 d group （P = 0.003）. There were no significant differences in plasma FIB and α2-AP concentrations among ru-PA 3 d group, rt-PA 3 d group and baseline values （ P = 0.655, P = 0.751 ）. Conclusions （ 1 ） Intravenous bolus injection of ru-PA （ 1 mg/kg） does not cause α2-AP consumption and fibrinogen breakdown at the early time. However, the injection of rt-PA 1 mg/kg may cause α2-AP consumption and fibrinogen breakdown at the early time. （2）The duration of PTE affects thrombolysis induced by ru-PA. The present study shows that ru-PA is much more potent for older clot lysis but less potent for fresh clot lysis than rt-PA.
出处
《中国呼吸与危重监护杂志》
CAS
2006年第5期341-344,共4页
Chinese Journal of Respiratory and Critical Care Medicine
