新型纤溶酶FA-Ⅰ抗血栓形成和溶栓作用研究

Effect of a Novel Fibrinolytic Enzyme FA-Ⅰ on Thrombosis and Thrombolysis

目的研究新型纤溶酶FA-Ⅰ在动物体内的抗凝血、抑制血栓形成和溶栓作用。方法建立小鼠抗凝血模型、大鼠静脉血栓形成模型和兔颈动脉血栓模型,分析三种模型中动物给予FA-Ⅰ后的凝血时间(CT)、凝血酶原时间(PT)、活化的部分凝血活酶时间(APTT)、凝血酶时间(TT)、优球蛋白溶解时间(ELT)和纤维蛋白原(FIG)含量,并分析其血液流变学指标。结果在三种模型中,FA-Ⅰ明显延长CT、PT、APTT和TT(P<0.05或P<0.01),显著降低ELT和FIG含量(P<0.01),并且能改善兔血液流变状态。结论FA-Ⅰ无论经静脉注射还是口服均能达到抗栓、溶栓之功效,其不但有望开发成实用的静脉注射溶栓药物,而且可以开发成安全的口服溶栓药物或保健品。

Objective To stduy the effect of FA-Ⅰ , a novel fibrinolytic enzyme isolated from the metabolite of Arthrobacter sp. DR-536, on thrombosis and thrombolysis in vivo. Methods The anticoagulated blood model of mise were administered with FA-Ⅰ orally. The venous thrombogenesis inhibition model of rats were administered with FA-Ⅰ by intestinal route. The carotid thrombosis model of rabbits were given FA-Ⅰ intravenously. The clotting time （CT）, protbrombin time （PT）, activated partial thromboplastin time （APTT）, thrombin time （TT）, Euglobulin lysis time （ELT）, fibrinogen （FIG） and hemorheology condition were analyzed. Results FA-Ⅰ prolonged the CT, PT, APTT and TT, and decreased ELT and FIG significantly （P〈0.05 or P〈0.01）. FA- Ⅰ also improved the hemorheology conditions in the rabbits. Conclusion Both intravenous injection and oral administration of FA- Ⅰ are effective in thrombosis and thrombolysis. FA- Ⅰ could become a pragmatic venoclysis thrombolytic drug or a peroral thrombolytic drug.