Bara L, Bloch M F, Samama M M
Laboratoire Thrombose Expérimentale, Faculté de Médecine, Paris, France.
Thromb Res. 1992 Oct 15;68(2):167-74. doi: 10.1016/0049-3848(92)90032-6.
The in vitro anticoagulant activity of recombinant desulphated hirudin (HBW 023) and its antithrombotic activity in a rabbit venous stasis model were assessed in comparison to unfractionated heparin (UH). The specific activity of r-hirudin in rabbit plasma is similar to that of unfractionated heparin on a weight basis when using the whole blood clotting time or APTT, while it was five times more potent according to the thrombin clotting time (TCT). Forty-eight (6x8) anaesthetized New Zealand male rabbits were randomized to receive HBW 023 (12.5, 25, 50, 100, 200, 400 micrograms.kg-1), standard heparin (90 micrograms.kg-1) or placebo. Five minutes after administration of the drug, the experimental thrombosis was induced by an injection of glass activated overnight human serum into the marginal vein of the ear and ligation of the jugular vein (Wessler model). The jugular vein was removed after 10 min stasis and examined by a researcher unaware of the treatment administered. In the Wessler stasis model the fresh thrombus weight and a score as well as the circulating level of r-hirudin using a chromogenic substrate assay were used to determine the inhibitory effect of the drug. Highly significant inverse correlations were found between fresh thrombus weight and the injected doses as well as r-hirudin plasma levels. The ID50 which was the dose of the drug that induced a complete inhibition of thrombosis in 50% of the dose group tests was about 200 micrograms.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)
将重组去硫酸化水蛭素（HBW 023）的体外抗凝活性及其在兔静脉淤滞模型中的抗血栓形成活性与普通肝素（UH）进行了比较评估。当使用全血凝固时间或活化部分凝血活酶时间（APTT）时，重组水蛭素在兔血浆中的比活性按重量计算与普通肝素相似，而根据凝血酶凝固时间（TCT），其效力要强五倍。将48只（6×8）麻醉的新西兰雄性兔随机分组，分别接受HBW 023（12.5、25、50、100、200、400微克·千克⁻¹）、标准肝素（90微克·千克⁻¹）或安慰剂。给药5分钟后，通过向耳缘静脉注射玻璃激活的过夜人血清并结扎颈静脉（韦斯勒模型）诱导实验性血栓形成。淤滞10分钟后取出颈静脉，由不知道所给予治疗的研究人员进行检查。在韦斯勒淤滞模型中，使用新鲜血栓重量、评分以及用显色底物法测定的重组水蛭素循环水平来确定药物的抑制作用。发现新鲜血栓重量与注射剂量以及重组水蛭素血浆水平之间存在高度显著的负相关。半数抑制剂量（ID50）即在50%的剂量组试验中诱导血栓形成完全抑制的药物剂量约为200微克·千克⁻¹。（摘要截断于250字）
