[Effect and mechanism of recombinant hirudin on fibrinolysis].
OBJECTIVE
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 99mTc 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 TAFIa, 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 ( < or = 0.2 u x mL(-1)), and the level of fibrinolysis product, D-Dimer, increased.


CONCLUSIONS
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.
Li
Ming
M
Key Laboratory of Industry Biotechnology of Ministry of Education, Southern Yangtze University, Wuxi 214036, China.
Zhang
Rong-jun
RJ
Cao
Guo-xian
GX
Wan
Wei-xing
WX
Zhang
Lian-fen
LF
Jin
Jian
J
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D025901:Carboxypeptidase B2 / Q000378:metabolism*; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D004285:Dogs; D005176:Factor XIII / Q000378:metabolism; D005263:Femoral Artery; D005268:Femoral Vein; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006629:Hirudins / Q000235:genetics / Q000494:pharmacology*; D008297:Male; D010940:Plant Proteins / Q000494:pharmacology; D011480:Protease Inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D018180:Thrombomodulin / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism*; D020246:Venous Thrombosis / Q000378:metabolism
D005343:Fibrinolytic Agents; D006629:Hirudins; D010940:Plant Proteins; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D018180:Thrombomodulin; D005176:Factor XIII; D002268:Carboxypeptidases; D025901:Carboxypeptidase B2