重组水蛭素促纤溶作用及其作用机制  

Effect and mechanism of recombinant hirudin on fibrinolysis

作　　者：黎明[1] 张荣军[2] 曹国宪[2] 万卫星[3] 张莲芬[1] 金坚[1] 

机构地区：[1]江南大学生物工程学院工业生物技术教育部重点实验室,江苏无锡214036 [2]江苏省原子医学研究所,江苏无锡214063 [3]苏州大学附属第四医院,江苏无锡214036

出　　处：《药学学报》2006年第9期814-818,共5页Acta Pharmaceutica Sinica

基　　金：江苏省自然科学基金资助项目(BK2001165)

摘　　要：目的研究重组水蛭素(recomb inant h irud in,rH)在纤溶过程中的作用及其可能的机制。方法采用同位素示踪技术,分析rH对动物血栓模型中凝血酶-纤维蛋白复合物的影响。采用tPA为纤溶激酶的体外溶栓模型,分析rH对纤溶的影响。结果标记了99mTc的犬股动、静脉血栓于30 m in开始显影,随后各时相血栓影像趋清晰;体外纤溶结果显示,rH添加组较对照组没有纤溶再凝现象。TM的添加显著延长纤溶时间,CPI可缩短由TAFI活化造成的纤溶时间的延长,rH的添加可以使TAFI的活化被抑制。较低浓度rH(≤0.2 u.mL-1)的添加使血浆中FX III的活化被抑制,并且使纤溶产物D-D im er的水平升高。结论rH可有效抑制结合在Fn上的Th;rH可以通过抑制TAFI和FX III的活化达到促进纤溶的作用。Aim To study the effect of recombinant hirudin （rH） on tPA-induced fibrinolysis and the possible mechanism of its action. Methods The effect of rH on thrombin-fibrin complex （Th-Fn） was detected by 99roTe labeled rH. In the in vitro clot lysis, tPA as plasminogen activator, and recalcified plasma as plasminogen resource were used to study the influence of rH on fibrinolysis by detecting TAFla, D-Dimer and FXⅢ. Results In a canine model of femoral artery thrombosis, a clear radioactivity strip was imaged in 30 -60 min on a part image, and the femoral vein thrombosis developed at 30 min. rH efficiently inhibited clot regeneration. Addition of TM could inhibit clot lysis obviously, and CPI could shorten the delay of clot lysis which due to TAFIa. There was a dose-dependent relationship with TM concentration and TAFI activation. FXⅢ activation was inhibited by low concentration of rH （ ≤0.2 u ·mL^-1）, and the level of fibrinolysis product, D-Dimer, increased. Conclusion rH could inhibit the thrombin binding to fibrin, rH inhibited the activation of TAFI and FXⅢ by combining with thrombin which resulted in enhancement of thrombolysis.

关 键 词：重组水蛭素 纤维蛋白 凝血酶激活的纤溶抑制物 XⅢ因子 

分 类 号：R963[医药卫生—微生物与生化药学]