新型合成水蛭肽Hirulog-s抗家兔弥散性血管内凝血的作用

Anti-DIC effect of Hirulog-s,a novel hirudin-derived anticoagulant peptide,in rabbits

目的:研究新型合成水蛭肽Hirulog-s抗弥散性血管内凝血(DIC)的作用。方法:采用凝血酶(100 U.kg-1×1 h)和氨基己酸(50 mg.kg-1×1 h)静脉滴注造成家兔急性DIC模型,观察给药前后家兔全血血小板计数(PLT)、血浆凝血酶原时间(PT)、纤维蛋白原(FIB)含量和血浆鱼精蛋白副凝固(3P)试验以及丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性,并采用放免测定法检测血浆血栓素(TXA2)和前列环素(PGI2)水平。结果:静脉注射高、中、低剂量(125.00,62.50,31.25μg.kg-1)Hirulog-s后DIC的抑制率用PT表示分别为69.72%,42.48%和24.48%;用PLT表示分别为62.13%,47.93%和31.52%;用FIB表示分别为66.73%,48.90%和28.19%;MAD含量显著下降,下降百分率分别为25.00%,14.47%和6.58%,SOD活性显著上升(P<0.01),上升百分率分别为198.52%,150.08%和42.05%;TXA2/PGI2比值显著下降(P<0.01),相同剂量的Hirulog-s的上述作用明显强于阳性对照药比伐卢定。结论:Hirulog-s具有明显的抗凝血酶诱发的DIC作用,其作用强于已上市同类药物比伐卢定。

Objective ： To investigate the antagonistic effect of Hirulog-s, a novel hirudin-derived peptide, on disseminated intravascular coagulation （DIC） in rabbits. Methods：Rabbit acute DIC model was induced by con- stant iv infusion of thrombin. The levels of PT,PLT,FIB and MDA,SOD activity, plasma TXA2/PGI2 ratio as well as 3P test before and after iv administration of Hirulog-s were used to examine the effect of Hirulog-s on DIC. The effect was compared with those of bivalirudin and heparin. Results： Hirulog-s at high （125.00 μg.kg^-1） ,middle （62.50 μg.kg^-1 ） and low （32.25 μg.kg^-1 ） doses resulted in a dose-dependent inhibition against DIC with inhibitory rates of 69.72% ,42.48% and 24.48% for PT,62. 13% ,47.93% and 31.52% for PLT,and 66.73% , 48.90% and 28.19% for FIB, respectively. After iv dosing,MDA was significantly reduced, SOD was markedly el- evated,while TXAJPGIz ratio was substantially decreased. The above effects of Hirulog-s were found to be more potent than the positive control drug bivalirudin at the same dosage. Conclusion：Hirulog-s has significant anti-DIC effects in rabbits with the potency exceeding bivalirudin.