重组纳豆激酶重复给药对Beagle犬凝血和纤溶系统的影响

目的:研究重组纳豆激酶(recombinant nattokinase,r-NK)大剂量重复给药对Beagle犬凝血和纤溶系统的影响。方法:用血细胞计数仪测定血小板相关参数;用血凝仪采取凝固法依次测定纤维蛋白原(Fib)含量、活化部分凝血酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT);ELISA法分别测定纤溶酶原(PLG)、纤溶酶原激活因子(t-PA)活性。结果:大剂量(2．24×10~5 u·kg~(-1))重复静脉注射r-NK可导致凝血障碍,引起多发性、弥漫性出血,最终导致动物死亡;给药后2周Beagle犬血小板计数均下降,PT明显延长,Fib含量均明显降低,PLG活性升高。结论: r-NK大剂量重复给药可破坏机体的凝血/纤溶系统平衡,导致Beagle犬凝血功能降低,纤溶系统功能异常增强。

Effects of recombinant nattokinase on coagulation and fibrinolytic function of Beagle dogs

Objective:To assess the effects of recombinant nattokinase (r-NK) on coagulation and fibrinolytic function of Beagle dogs.Methods:Beagle dogs were administered with multiple and large doses of r-NK.Platelet parameters were analyzed by a blood analyzer.The fibrinogen (Fib),acti- vated partial thrombin time (APTT),prothrombin time (PT) and thrombin time (TT) were determined using a coagulation detector.Plasminogen (PLG) and tissue-type plasminogen activator (t-PA) were tested by ELISA.Results:The r-NK-treated dogs experienced severe coagulation impediment,multiple and diffused bleeding,and even death.In two weeks post the administration,the dogs showed significant reduction of platelets number,PT prolongation and escalation of both Fib concentration and the activity of PLG.Conclusion:The multi and large dosing of r-NK imbalanced the coagulation and fibrinolysis sys- tem,leading to weaker coagulation and abnormally higher fibrinolytic function.