Effect and mechanism of recombinant hirudin on fibrinolysis.
- Author:
Ming LI
1
;
Rong-jun ZHANG
;
Guo-xian CAO
;
Wei-xing WAN
;
Lian-fen ZHANG
;
Jian JIN
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Blood Coagulation; drug effects; Carboxypeptidase B2; metabolism; Carboxypeptidases; antagonists & inhibitors; Dogs; Factor XIII; metabolism; Femoral Artery; Femoral Vein; Fibrinolysis; drug effects; Fibrinolytic Agents; pharmacology; Hirudins; genetics; pharmacology; Male; Plant Proteins; pharmacology; Protease Inhibitors; Recombinant Proteins; pharmacology; Thrombomodulin; metabolism; Thrombosis; metabolism; Venous Thrombosis; metabolism
- From: Acta Pharmaceutica Sinica 2006;41(9):814-818
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo study the effect of recombinant hirudin (rH) on tPA-induced fibrinolysis and the possible mechanism of its action.
METHODSThe 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.
RESULTSIn 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.
CONCLUSIONrH 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.
