Studies On Anti-artery Thrombotic Effect And Anti-DIC Effect Of Hirulog-s, A Novel Hirudin-derived Peptide, In Animals

Objective: To investigate the effects of Hirulog-s, a novel hirudin-derived peptide, on anti-coagulation, anti-artery thrombosis and improving hemorrheology in rats, on anti-disseminated intravascular coagulation (DIC) in rabbits in order to provide preclinical pharmacological basis for its development as a new drug.Methods: CT, TT, PT and APTT were determined to examine the effect of Hirulog-s on anti-coagulantion. Occlusion Time ( OT ) and blood viscosity, plasma viscosity were measured to investigate its effects on anti-thrombosis and hemorrheology. The above blood parameters were measured after iv administration of Hirulog-s at low (0.5), middle (1.0) and high (2.0 mg/kg) doses to rats in comparation with positive drug Bivalirudin, Heparin, LAS and Pentoxifylline. Rabbit acute DIC was induced by iv infusion of thrombin and PT, PLT, FIB, 3P test and MDA, SOD as well as plasma TXA2/PGI2 ratio were measured to examine the effect of Hirulog-s on DIC in comparation with positive drug Bivalirudin and Heparin.Results: Hirulog-s prolonged TT, PT and APTT, dose-dependently. After iv dosing, OT was significantly and dose-dependently prolonged, with the action duration of 8 h. Hirulog-s decreased blood viscosity(high shear rate and low shear rate), plasma viscosity markedly. iv administration of Hirulog-s at high (125.00), middle (62.50) and low (32.25μg/kg) doses to rabbits resulted in a dose-dependent inhibition against DIC with inhibitory rate being 69.72, 42.48 and 24.48 % (PT), 62.13, 47.93 and 31.52 % (PLT), and 66.73, 48.90 and 28.19 % (FIB). After iv dosing, MDA was significantly reduced, SOD was markedly elevated, TXB2/6-keto-PGF1αratio was substantially descended. Conclusion: Hirulog-s has significant effects on anti-coagulantion, anti-artery thrombosis and improving hemorrheology in rats,on anti-acute-DIC induced by thrombin in rabbits.