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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 study the effect of Hirulog-s against disseminated intravascular coagulation (DIC). Methods: Acute DIC model was induced by intravenous drip of thrombin (100 U.kg-1 × 1 h) and aminocaproic acid (50 mg.kg-1 × 1 h) in rabbits. The levels of whole blood platelets (PLT), plasma prothrombin time (PT), fibrinogen (FIB) and plasma protamine co-coagulation (3P) test and malondialdehyde (MDA) content, superoxide dismutase (SOD) , And the level of plasma thromboxane (TXA2) and prostacyclin (PGI2) were measured by radioimmunoassay. Results: The inhibitory rates of DIC after high, medium and low dose (125.00, 62.50, 31.25μg.kg-1) Hirudo-s were 72.7%, 42.48% and 24.48%, respectively; %, 47.93% and 31.52%, respectively. The contents of MAD were decreased by 66.73%, 48.90% and 28.19%, respectively. The percentages of MAD were decreased by 25.00%, 14.47% and 6.58%, respectively. (P <0.01). The above effects of Hirulog-s at the same dose were obviously stronger than the positive control bivalirudin. Conclusion: Hirulog-s has obvious anticoagulant-induced DIC effect, its effect is stronger than the already-listed similar drugs bivalirudin.