重组水蛭素Ⅲ乳化微粒口服的药效学

 目的探讨重组水蛭素Ⅲ乳化微粒(rHVⅢEP)口服的抗凝血、抗血栓作用。方法①将SD大鼠随机分为4组,分别为水蛭素大、小剂量组(65,130U·g^-1),华法林钠阳性对照组和生理盐水组。分别于给药前、后1h各取血1.5～2mL,测定凝血时间(CT)、血浆凝血酶原时间(PT)、凝血酶凝固时间(TT)、活化部分凝血活酶时间(APTT);②采用大鼠弥散性血管内凝血模型,测定PT、TT、APTT;③动物分组如上,采用大鼠下腔静脉血栓模型,测定血栓湿重和干重,计算血栓抑制率;④动物分组如上,采用大鼠颈动静脉回路形成的血小板性动脉血栓模型,测定血栓湿重,计算血栓抑制率。结果①rHVⅢEP能延长CT、PT、TT、APTT,与空白对照组有显著差异(P<0.05或P<0.01);②rHVⅢEP能延长大鼠弥散性血管内凝血模型PT、TT、APTT,并与生理盐水组有显著差异;③rHVⅢEP口服可使大鼠下腔静脉血栓湿重、干重明显减少,血栓抑制率显著升高,与生理盐水组有显著差异;④rHVⅢEP口服可使大鼠颈动静脉回路形成的血小板性动脉血栓重量明显减少,显著升高血栓形成抑制率,与生理盐水组有显著差异。结论rHVⅢEP口服抗凝血、抗血栓作用显著,可用于防治实验性大鼠弥散性血管内凝血、大鼠颈动静脉回路形成的血小板性动脉血栓和大鼠下腔静脉血栓,具有良好的应用前景。

Pharmacodynamics of Recombinant Hirudin Ⅲ Emulsive Microparticles After Oral Administration

OBJECTIVE To investigate the effect of recombinant hirudin-Ⅲ emulsive microparticles (rHVⅢ EP) on anticoagulation and antithrombin after oral administration. METHODS ①SD(Sprague Dawley) rats were divided into four groups which were treated with high and low dose (65 and 130 U·g^-1) rHVⅢ EP, Warfarin sodium and saline group respectively. 1.5～2.0 mL Blood was taken before and at 1 h after oral administration of rHVⅢ EP. The clotting time(CT), thrombin time (TT), activated partial thromboplastin time (APTT ),and prothrombin time (PT ) were measured respectively; ②The intravascular cougulation rats were divided into four groups which were treated with high and low doses rhVⅢEP (65 and 130 U·g^-1), warfarin sodium and saline. TT, APTT and PT were measured in disseminated intravascular coagulation rats after oral administration of rHVⅢ EP; ③The A-V circulation rats were treated with high and low doses of rhVⅢ EP(65 and 130 U·g^-1), warfarin sodium and saline. The wet and dry weight of thrombus were measured in inferior vena cava thrombosis rats after oral administration of rHVⅢ EP. The inhibition ratio of thrombus was calculated. ④The inferior vena cava thrombosis rats were treated with high and low doses of rHVⅢ (65 and 130 U·g^-1), warfain sodium and soline. The wet and dry weight of thrombus was measured in A-V circulation rats after oral administration of rHVⅢ EP. The inhibition ratio of thrombus was calculated. RESULTS ①CT, TT, APTT and PT were prolonged significantly after oral administration of rHVⅢ EP; ②TT, APTT and PT were strengthened significantly in inravascular coagulation rats after oral administration of rHVⅢ EP; ③The weight of wet and dry thrombus were reduced in inferior vena cava thrombosis rats after oral administration of rHVⅢ EP and the obvious inhibition was observed;④The weight of thrombus in A-V circulation rats was reduced after administration and the obvious inhibition was observed. CONCLUSION rHVⅢ EP has strong activity of anticoagultion after oral administration. rHVⅢ EP could be used successfully via oral route.