重组葡激酶溶栓活性的实验研究

The experimental study on recombinant staphylokinase

目的探讨重组葡激酶(r-Sak)的溶栓活性及对纤维蛋白溶解系统的影响。方法通过对家兔内膜受损颈动脉内注射凝血酶产生的富红细胞血栓形成动物模型(21只),分别给予0.5ml/kg生理盐水(NS)(对照组5只)、27500IU/kg尿激酶(UK)(阳性对照组8只)及27500AU/kg r-Sak(实验组8只),比较各组用药前、后颈动脉血流量(CBF)的变化及对纤维蛋白溶解系统指标的影响。结果r-sak对颈动脉富红细胞血栓产生明显的溶栓作用,与等剂量UK比较,出现再通所需时间短(18.3±5.9min VS 28.6±3.5min,P<0.01),实验组用药后CBF最大值(Max)与用药前CBF值的差(△)较阳性药对照组有显著性差异(5.14±0.61m1/min VS 3.31±0.95 ml/min,P<0.001);同时,r-Sak对凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、α-抗纤维蛋白溶解酶(α-AP)活性、纤维蛋白原(Fg)、纤维蛋白溶解酶原(Pg)等凝血及纤维蛋白溶解系统指标均无明显影响(P>0.05)。阳性对照组和实验组中各有25％(2/8)发生了动脉穿刺点渗血,均于20min内自行停止。结论 国产r-Sak作为一种新型的纤维蛋白选择性溶栓剂,有可能为临床溶栓治疗提供新的手段,且无严重副作用,值得作进一步研究。

Objective To investigate the effect of thrombolysis and influence to fibrinolytic system with recombinant staphylokinase(r-Sak). Methods In this experiment, thrombin was injected into rabbit's carotid whose endangium was injuried and set up animal models developed red cell-rich thrombi. Using r-Sak of 27500AU/kg in experimental group (8 cases),urokinase (UK) of 27500IU/kg in positive control group (8 cases) and normal saline(NS) of 0. 5ml/kg in common control group, compared carotid blood flow(CBF) before and after using drugs and observed the change of fibrinolytic system in the three groups. Results The administration of r-Sak produced an obvious fibrinolytic effect to red cell-rich thrombi in carotid. Compared with the same dose of UK, the time of reperfusion in experimental group become shorter (18. 3+5. 9min VS 28. 6+3. 5 min, P<0. 01). Difference(A)between the maximum of CBF after using drugs and the value of CBF before using drugs in experimental group is higher than that in positive control group (5. 14+0. 61ml/min vs 3. 31+0. 95 ml/min, P<0. 001). At same time, r-Sak had no obvious influence to any indexes of coagulation and fibrinolysis system such as prothrombin time (PT), APTT, a2-anti-plasmin (a,-AP) ,fibrinogen(Fg)and plasminogen(Pg). In the animal's experiment, 2 of 8 (25%) with bleeding in puncture area in experimental group and positive control group, respectively. It could spontaneously end within 20 min. Conclusions Domestic r-Sak,as a new fibrinolytic agent with high fibrin(Fi)-specific, would be a new way in the field of thrombolysis and have not any serious side effect. It is valuable to study the medicine in the future.