摘要
目的:研究重组水蛭素(recombinanthirudin,rH)的抗弥散性血管内凝血(DIC)的作用。方法:♂大耳白兔,采用凝血酶(100U·kg-1·1h)和氨基已酸(50mg·kg-1·h-1×1h)静脉滴注造成急性DIC模型,观察rH对凝血酶原时间(PT)、血小板计数(PLT)、纤维蛋白原(FIB)含量和血浆鱼精蛋白副凝固(3P)试验以及肺、肾微血栓形成的影响。结果:4个剂量的rH(125、62.5、31.25和15.625μg·kg-1)对于DIC的抑制率:用PT表示分别为89.38、52.60、49.71和25.58;用PLT表示分别为100.01、61.86、58.40和32.68;用FIB表示分别为85.22、73.01、33.60和14.86。各剂量组的肺、肾病理切片均未见微血栓形成。当rH剂量为125μg·kg-1时,试验中各项指标均与生理盐水空白对照组一致。结论:国产rH具有强大的抗DIC作用,其作用强度与已被欧共体批准上市的产品重组水蛭素Refludan相同。
AIM: To investigate the anti-DIC effect of the domestic recombinant hirudin (rH) in order to provide preclinical pharmacological basis for its new drug application. METHODS: DIC was induced by constant iv infusion of thrombin (100 U · kg^-1 · h^-1 × 1 h) plus PAMBA (50 mg · kg^-1· h^-1 × 1 h). Platelet count (PLT), PT and fibrinogen (FIB) determination as well as plasmaprotamine paracoagulation (3P) test served as diagnostic indexes of DIC, while pathlogical examination of microthrombosis of lungs and kidneys was followed. RESULTS: rH 125,62.5,31.25 and 15. 625 μg · kg^-1 iv. gtt demonstrated a dose-dependant inhibitory effect on DIC. The inhibitory effects on DIC of rH(% ) were 89.38%, 52.60%, 49.71% and 25.58% for PT, and 100.01%, 61.86%, 58.40% and 32.68% for PLT, and 85.22%, 73.01%, 33.60% and 14.86% for FIB respectively at the descending order of rH doses. CONCLUSION: Domestic rH being tested has powerful anti-DIC effect which is comparable with refiudan--an r-hirudin product approved by European Community for marketing.
出处
《中成药》
CAS
CSCD
北大核心
2005年第10期1182-1186,共5页
Chinese Traditional Patent Medicine
关键词
重组水蛭素
弥散性血管内凝血
药效学
recombinant hirudin(rH)
disseminated intravascular coagulation(DIC)
pharmacological studies