海洋微生物代谢产物FGFC1的纤溶促进作用

Fibrinolysis promoting activity of a novel metabolic product of marine microbe-FGFC1

目的：研究海洋微生物产生的吡喃并异吲哚酮化合物FGFC1体外和实验动物体内促纤溶作用。方法：采用异硫氰酸荧光素（FITC）-纤维蛋白降解法和急性肺血栓大鼠模型法研究FGFC1体外和体内的纤溶促进作用。结果：在体外FITC-纤维蛋白降解实验中,FGFC1在0.5~25μmol/L浓度范围内,其纤溶促进作用随着浓度升高逐渐增强;当FGFC1浓度≥25μmol/L时,其纤溶促进作用维持在最高水平,EC50为5μmol/L。在大鼠急性肺血栓实验中,FGFC1的剂量为5或10mg/kg能溶解肺血栓,达到与5nmol/L剂量单链尿激酶型纤溶酶原激活剂相当的溶栓效果。结论：溶栓药物先导化合物FGFC1具有优良的纤溶促进作用和溶栓效果。

Objective：To study in vitro and in vivo the fibrinolysis promoting activity（FPA）of FGFC1,apyrylium isoindolinone compound of marine microbial origin.Methods：Fluorescein isothiocyanate（FITC）-fibrin degradation and acute pulmonary embolism model of rats were used invitroand in vivo to study the FPA of FGFC1.Results：In the in vitro FITC-fibrin degradation experiment,FPA of FGFC1 within the levels of 0.5-25μmol/L increased with the increase of FGFC1.When the level of FGFC1was≥25μmol/L,FPA was maintained at its peak level and the EC50 was 5μmol/L.In acute pulmonary embolism model of rats,FGFC1 showed thrombolysis activity with an injection dose of 5 mg/kg and 10 mg/kg.The thrombolysis effect of FGFC1 reached pro-urokinase-type plasminogen activator of 5nmol/L.Conclusion：FGFC1showed excellent fibrinolysis promotion and thrombolysis effects as a candidate lead compound of thrombolytic agents.