不同途径溶栓抗凝治疗下肢深静脉血栓的实验研究

Effects of different ways of thrombolytic and anticoagulant therapy on lower extremity deep venous thrombosis in rabbits

目的:通过建立兔下肢深静脉血栓模型,研究不同途径抗凝、溶栓治疗兔下肢深静脉血栓的疗效,同时动态观察D二聚体(DD)变化对溶栓疗效判断的意义。方法:采用结扎法建立深静脉血栓模型,将36只新西兰兔随机分为3组,A组经患侧腘静脉置管抗凝溶栓,B组经患侧股动脉置管抗凝溶栓,C组经外周静脉系统抗凝溶栓。给予尿激酶500U/(kg·h),肝素钠10U/(kg·h),微量泵持续24h,分别于给药前,给药4、8、12、16、20、24h测定血浆DD值。24h后造影观察血管再通情况。结果:A、B、C组在给药后DD水平均出现先上升后下降的变化,A组在12h达到高峰,24h后恢复至溶栓前水平,B、C组均在20h时达到高峰,随后出现下降,24h后仍明显高于溶栓前水平。3组在治疗前DD水平无明显统计学差异(P>0.05),A组在4、8、12、20、24h与B、C组相同时间点比较差异均有显著性(P<0.05)。而B、C两组在各相同时间点比较均无明显差异(P>0.05)。血管造影,A组在24h后造影全部通畅,有效率100%,B组有效率为50%,C组有效率为58%,A组与B组或C组相比差异均有显著性(P<0.05)。B组与C组无明显差异(P>0.05)。结论:经腘静脉导管直接抗凝、溶栓对于下肢深静脉血栓的近期治疗效果优于经外周静脉系统抗凝溶栓及经股动脉置管溶栓;动态观察DD变化可以作为抗凝、溶栓的给药指导及治疗效果的评价指标。

Objective To investigate the therapeutic effects of the three different ways of thrombolytic and anticoagulant therapy on lower extremity deep venous thrombus （DVT） in rabbit DVT model and the clinical significance of dynamic monitor of serum D-dimer （DD） in the thrombolytic therapy. Methods According to the administrative ways of thrombolysis, thirty-six New Zealand rabbits were randomly divided into Group A （popliteal vein）, Group B （the femoral artery） and Group C （the peripheral vein）, The rabbit model of DVT was induced by ligation All the three groups received the same dose of urokinase and heparin through the micro pump. The serum DD levels were tested before and after 4, 8, 12, 16, 20 and 24 h after administration. Venogramphy was performed 24 hours later. Results Serum DD in all three groups increased at the beginning and decreased in the end. Group A reached the peak at 12 hour and returned to the pre-administration level at 24 hour after administration. Group B and C reached the peak at 20 hour and decreased later, but remained higher than pre-administration. There was no statistic difference （P 〉 0.05） of serum DD among three groups before therapy, but there were significant differences （P 〈 0.05） at 4, 8, 12, 20 and 24 h after administration between Group A and B or Group A and C. There were no statistic differences between Group B and C. Venogramphy showed 100% recanalization in Group A, 50% in Group B and 58% in Group C. There were significant differences （P 〈 0.05） between Group A and B or Group A and C, and no statistic differences （P 〉 0.05） between Group B and C. Conclusions It is suggested that the direct administration of thrombolytic and anticoagulant drugs through the popliteal vein has a better short-term outcome compared to the way through the femoral artery or the peripheral vein. Dynamic monitor of serum DD can be a reliable method to predict the administration of thrombolytic and anticoagulant drugs and to evaluate the therapeutic outcome.