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Effects of Tianma Xingnao capsule on thrombosis and coagulation system

天麻醒脑胶囊的溶栓作用及对凝血系统的影响


目的:探讨天麻醒脑胶囊的溶栓作用及其初步机制,同时评价其对凝血系统的影响。方法:采用改良的Charlton和Tomihisa方法评价天麻醒脑胶囊对电刺激大鼠颈动脉血栓的溶栓作用;应用ELISA方法测定天麻醒脑胶囊对家兔血浆组织型纤溶酶原激活物(tPA)和纤溶酶原激活物抑制物(PAI 1)活性的影响。同时评价PUW对家兔优球蛋白溶解时间(ELT)、凝血酶原时间(PT) 、白陶土部分凝血活酶时间(KPTT) 、凝血酶时间(TT)、纤维蛋白原(Fib)含量和血液流变学的影响。结果:06,12 g·kg-1天麻醒脑胶囊的再通率分别为40%,50%,再栓率分别为50%,40%;03 g·kg-1的天麻醒脑胶囊对再通率和再栓率均无明显作用。05,10 g·kg-1的天麻醒脑胶囊于末次给药后60,120 min均明显抑制血浆PAI 1活性,60(180 min 显著提高血浆tPA活性。1 g·kg-1天麻醒脑胶囊于给药后60,120 min可明显缩短ELT,025,05 g·kg-1的剂量则无明显影响。05,10 g·kg-1的天麻醒脑胶囊显著延长KPTT和PT,明显降低Fib水平;3种剂量的天麻醒脑胶囊对TT及红细胞电泳、高切、中切和低切均无明显影响。结论:天麻醒脑胶囊显著提高闭塞颈动脉的再通率,同时降低再通后颈动脉的再栓率;抑制 PAI 1活性,同时提高tPA的活性可能是其具有较好溶栓作用的分子机制。天麻醒脑胶囊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。

Objective: This study investigated the thrombolitic effect of Tianma Xinnao capsule and its preliminary mechanism, as well as the effect on coagulation system.  Method: Charlton‘s and Tomihisa‘s methods were modified to investigate the thrombolytic effect of Tianma Xinnao capsule. The activities of type 1 plasminogen activator inhibitor (PAI 1) and tissue type plasminogen activator (tPA) in rabbit plasma were assayed by use of ELISA. The effects of Tianma Xinnao capsule were also evaluated on euglobulin lysis time (ELT), prothrombin time (PT), kaolin partial thromboplastin time (KPTT), thrombin time (TT), fibrinogen (Fib) and hemorheology.   Result: The results showed that Tianma Xinnao capsule had a dose dependent thrombolytic effect in rats. Tianma Xinnao capsule at 06 and 12 g·kg-1 produced 40% and 50% of reperfusion rate, while obtained 50% and 40% of reocclusion rate; 03 g·kg-1 of Tianma Xinnao capsule, however, had no effect on the reperfusion or reocclusion rate. Tianma Xinnao capsule significantly inhibited PAI 1 activity, while elevated tPA activity in rabbit plasma. Tianma Xinnao capsule markedly prolonged ELT, PT, and KPTT, and decreased Fib level. Tianma Xinnao capsule showed no significant influence on TT or high, medium, or low sheering viscosity.  Conclusion: It is indicated that Tianma Xinnao capsule inhibited PAI 1 activity and increased tPA activity, and this property of Tianma Xinnao capsule is assigned to be responsible for the thrombolytic effect.