不同尿激酶溶栓方案对肺血栓栓塞症模型犬肺功能及凝血指标的影响

Effects of different thrombolytic regimens with urokinase on pulmonary function and hemorheology in animal models of pulmonary thromboembolism

目的探讨不同尿激酶(UK)溶栓方案对肺血栓栓塞症(PTE)模型犬肺功能及凝血指标的影响。方法选择健康杂种犬36只,随机分为六组,即空白对照组(A组)、模型组(B组)、UK 12 h溶栓小剂量组(5 000 U/kg,C1组)、UK 12 h溶栓大剂量组(10 000 U/kg,C2组)、UK 2 h溶栓小剂量组(5 000 U/kg,D1组)、UK 2 h溶栓大剂量组(10000 U/kg,D2组),每组6只。B组至D2组注入血凝块悬浊液建立PTE模型,C1、C2、D1、D2分别给予相应药物输入处理。监测溶栓前后六组平均肺动脉压(mPAP)、动脉血氧分压(PaO_2)变化,栓塞前后留取血清,测定活化部分凝血活酶时间(APTT)、凝血酶原时间(PT),测定血栓素A2(TXA2)、前列环素(PGI2)的变化。结果(1)栓塞后,B组、C1组、C2组、D1组、D2组m PAP上升(P<0.05);溶栓后2 h,C1组、C2组、D1组、D2组m PAP均降低,D2组降低幅度高于其他各组(P<0.05);(2)栓塞后,B组、C1组、C2组、D1组、D2组PaCO_2降低(P<0.05);溶栓后2 h,C1组、C2组、D1组、D2组均上升,D1、D2组上升幅度高于C1、C2组,D2组上升幅度最高(P<0.05);(3)栓塞后,B组、C1组、C2组、D1组、D2组PT、APTT均缩短(P<0.05);溶栓后2 h,C1组、C2组、D1组、D2组均延长,C2组、D1组、D2组PT与栓塞后比较差异有统计学意义(P<0.05),D1、D2组溶栓后2 h APTT与栓塞后比较差异有统计学意义(P<0.05),D2组溶栓后2 h PT、APTT延长幅度高于其他各组(P<0.05);(4)栓塞后,B组、C1组、C2组、D1组、D2组TXA2、PGI2均上升(P<0.05);溶栓后2 h,C1组、C2组、D1组、D2组TXA2、PGI2下降,D1、D2组下降幅度高于C1、C2组,D2组下降幅度最高(P<0.05)。结论犬肺栓塞后,采用2 h UK大剂量溶栓方案,可下调TXA2、PGI2,降低m PAP,上调PaO_2,改善凝血功能。

Objective To investigate the effects of different thrombolytic regimens with urokinase （UK）on pulmonary function and hemo-rheology in animal models of pulmonary thromboembolism （PTE）. Methods 36 healthy hybrid dogs were selected and randomized into 6 groups, namely,the blank control group （group A）,model group （group B）,12 h thrombolysis with small - dose UK group （5000 U/ kg,group C1）, 12 h thrombolysis with large - dose UK group （10000 U/ kg,group C2）,2 h thrombolysis with small - dose UK group （5000 U/ kg,group D1） and 2 h thrombolysis with large - dose UK group （10000 U/ kg,group D2）,6 dogs in each group. Group B to D2 were injected with clot suspen-sion to establish PTE model,C1,C2,D1,D2 were given the corresponding drug input processing. The changes of mean pulmonary arterial pres-sure （mPAP）and arterial partial pressure of oxygen （PaO2 ）before and after thrombolysis in 6 groups were monitored. The serum was collected before and after embolization to determine activated partial thromboplastin time （APTT）and prothrombin time （PT）. Changes of thromboxane A2 （TXA2）and prostacyclin （PGI2）were also determined. Results ①After embolization,mPAP of group B,C1,C2,D1 and D2 increased （P〈 0. 05）;2 h after thrombolysis,mPAP of group C1,C2,D1 and D2 decreased,and the decreased range in group D2 was lower than the other groups （P 〈 0. 05）. ②After embolization,PaO2 of group B,C1,C2,D1 and D2 decreased （P 〈 0. 05）. 2 h after thrombolysis,PaO2 of group C1,C2,D1 and D2 increased,and the increased ranges in group D1 and D2 were significantly greater than those in group C1 and C2. The in-creased range in group D2 was the greatest （P 〈 0. 05）. ③After embolization,PT and APTT of group B,C1,C2,D1 and D2 was shortened （P 〈 0. 05）. 2 h after thrombolysis,PT and APTT of group C1,C2,D1 and D2 was prolonged. There were significant differences in PT of group C2,D1 and D2,compared with that after embolization （P 〈 0. 05）. 2 h after thrombolysis,there were significant differences in APPT of group D1 and D2,compared with that after embolization （P 〈 0. 05）. 2 h after thrombolysis,the prolonged ranges of PT and APTT in group D2 were greater than those in the other groups （P 〈 0. 05）. ④After embolization,TXA2 and PGI2 levels in group B,C1,C2,D1 and D2 were in-creased （P 〈 0. 05）. 2 h after thrombolysis,TXA2 and PGI2 levels in group C1,C2,D1 and D2 decreased. The decreased ranges in groupD1 and D2 were greater than those in group C1 and C2,and the decreased range in group D2 was the greatest （P 〈 0. 05）. Conclusion After pul-monary embolism in dog,application of 2h thrombolysis with large - dose UK can lower TXA2 and PGI2,reduce mPAP,upregulate PaO2 and im-prove blood coagulation function.