扎冲十三味丸的溶栓作用机制及对凝血系统的影响

Thrombolytic mechanism and effects on blood coagulation of mongolian medicine Zhachong Shisan( Zha Chong pills of thirteen ingredients)

目的：探讨扎冲十三味丸的溶栓作用及其初步机制,同时评价其对凝血系统的影响及急性毒理试验。方法：采用体内和体外溶栓的方法评价扎冲十三味丸对电刺激大鼠颈动脉血栓的溶栓作用;应用ELISA方法测定扎冲十三味丸对家兔血浆组织型纤溶酶原激活物（t PA）和纤溶酶原激活物抑制物（PAI-1）活性的影响;同时评价扎冲十三味丸凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、凝血酶时间（TT）、纤维蛋白原（Fib）含量和血液流变学的影响。扎冲十三味丸对实验小鼠的急性毒理试验。结果：0.432 g·kg^-1（中）和0.864 g·kg^-1（高）扎冲十三味丸组于末次给药后2-6 h均明显抑制血浆PAI-1活性,显著提高血浆t PA活性。0.864,1.728 g·kg^-1组和复方丹参滴丸0.12 g·kg^-1组明显降低Fib水平,明显延长TT,3种剂量的扎冲十三味丸对APTT和PT无明显影响,对红细胞电泳、高切、中切和低切均无明显影响;全部小鼠健存,无中毒反应。结论：扎冲十三味丸抑制PAI-1活性,同时提高t PA的活性可能是其具有较好溶栓作用的分子机制。扎冲十三味丸可影响内凝和外凝系统,减少血管壁纤维蛋白的沉积,也提示在临床用药过程中,有可能发生出血倾向,需密切监测患者的凝血系统;无明显急性毒理反应。

OBJECTIVE To investigate the thrombolytic effect of Zhachong Shisan and its preliminary mechanism, and evaluate its effects on blood coagulation and acute toxicity. METHODS Thrombolysis therapies in vivo and in vitro were applied to evaluate the thrombolytic effect of Zhachong Shisan on electrically stimulated carotid artery thrombosis in rats. The ELISA method was used to investigate the activities of plasma tissue-type plasminogen activator （tPA） and type 1 plasminogen activator inhibitor （PAI-1） in rabbit plasma. The effects of Zhachong Shisan were also evaluated on prothrombin time （PT）, activated partial thromboplastin time （APTT）, thrombin time （TT）, fibrinogen （Fib） and hemorheology. Acute toxicity of Zha chong Shisan on mice were also assessed. RESULTS After last administration, Zhachong Shisan 0. 864 g · kg ^-1 （moderate dose） and 0. 432 g· kg^-1 （high dose） could significantly inhibit PAI-1 activity and increase tPA activity in plasma 2 - 6 hours later. Zhachong Shisan 1. 728,0. 864 g·kg^-1 and Danshen Dripping Pills 0. 12 g·kg^- 1 could significantly decrease Fib level and prolong TT; 3 doses of Zhachong Shisan had no significant effect on APTT or PT, or on erythrocyte electrophoresis, high, moderate or low shear. All mice survived without toxic responses. CONCLUSION Zhachong Shisan can inhibit PAI-1 activity and increase tPA activity, which may be the molecular mechanism of better thrombolytie effects. Zhachong Shisan may affect the internal and external coagulation systems, reduce deposition of fibrin on vascular wall, which also suggests that hemorrhage tendency exists during clinical medication, and close monitoring is necessary. The drug has no acute toxic effects.