Fu Jieying, Ren Jianping, Zou Libo, Bian Guangxing, Li Ruifu, Lu Qiujun
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, China.
Thromb Res. 2008;122(5):683-90. doi: 10.1016/j.thromres.2008.01.007. Epub 2008 Mar 6.
Miniplasmin was a des-kringle variant of plasminogen with potential pharmacological application. We investigated the thrombolytic effect of miniplasmin in a canine model of femoral artery thrombosis.
In anesthetized dogs, a stable occlusive thrombus was formed by mechanical and electrolytic injury of the vessel wall, that the animals were later injected with miniplasmin (0.75 mg/kg, 1.5 mg/kg and 3.0 mg/kg, i.a.) and rt-PA (0.5 mg/kg, i.a.) intra-arterially. Hemodynamic parameters and hemorrhage status were monitored for 2 h. Thrombin time, activated partial thromboplastin time, prothrombin time and fibrinogen concentration were tested at 2 h after administration. Fibrin degradation product and D-dimer concentration were tested by ELISA.
The incidence of reperfusion in the miniplasmin (3.0 and 1.5 mg/kg) groups was 100%, and time to reperfusion was (3.3+/-1.0) and (7.0+/-2.3) min, which was shorter than rt-PA. After reperfusion, none of the vessels in the miniplasmin (1.5 and 3.0 mg/kg) groups reoccluded, whereas 20% of vessels reoccluded in the rt-PA group. Rudimental thrombus mass in the miniplasmin (1.5 and 3.0 mg/kg) groups were smaller than rt-PA. The operative wounds in all miniplasmin groups had no hemorrhage within 2 h. There were no significant differences in thrombin time, activated partial thromboplastin time and prothrombin time. Fibrinogen concentration in the miniplasmin (3.0 mg/kg) group reduced significantly as compared with baseline and thrombosis values, whereas these values in the miniplasmin (1.5 and 0.75 mg/kg) groups were unchanged. Fibrin degradation product and D-dimer concentration increased significantly after thrombolysis.
The results suggest that miniplasmin may be useful for the treatment of thrombosis and without complication of hemorrhage. This is in contrast to rt-PA, which intrinsically has a higher risk of occurring the hemorrhage risk.
微型纤溶酶是纤溶酶原的一种去kringle变体，具有潜在的药理学应用价值。我们在犬股动脉血栓形成模型中研究了微型纤溶酶的溶栓作用。
在麻醉的犬中，通过血管壁的机械和电解损伤形成稳定的闭塞性血栓，随后动物经动脉注射微型纤溶酶（0.75毫克/千克、1.5毫克/千克和3.0毫克/千克）和重组组织型纤溶酶原激活剂（0.5毫克/千克）。监测血流动力学参数和出血情况2小时。给药后2小时检测凝血酶时间、活化部分凝血活酶时间、凝血酶原时间和纤维蛋白原浓度。通过酶联免疫吸附测定法检测纤维蛋白降解产物和D - 二聚体浓度。
微型纤溶酶（3.0毫克/千克和1.5毫克/千克）组的再灌注发生率为100%，再灌注时间分别为（3.3±1.0）分钟和（7.0±2.3）分钟，比重组组织型纤溶酶原激活剂组短。再灌注后，微型纤溶酶（1.5毫克/千克和3.0毫克/千克）组的血管均未再闭塞，而重组组织型纤溶酶原激活剂组有20%的血管再闭塞。微型纤溶酶（1.5毫克/千克和3.0毫克/千克）组的残留血栓量比重组组织型纤溶酶原激活剂组小。所有微型纤溶酶组的手术伤口在2小时内均无出血。凝血酶时间、活化部分凝血活酶时间和凝血酶原时间无显著差异。微型纤溶酶（3.0毫克/千克）组的纤维蛋白原浓度与基线值和血栓形成时的值相比显著降低，而微型纤溶酶（1.5毫克/千克和0.75毫克/千克）组的这些值未改变。溶栓后纤维蛋白降解产物和D - 二聚体浓度显著升高。
结果表明，微型纤溶酶可能对血栓形成的治疗有用且无出血并发症。这与重组组织型纤溶酶原激活剂相反，后者本身有较高的出血风险。
