Aoki Y, Takei R, Mohri M, Gonda Y, Gomi K, Sugihara T, Kiyota T, Yamamoto S, Ishida T, Maruyama I
Institute for Life Science Research, Asahi Chemical Industry, Shizuoka, Japan.
Am J Hematol. 1994 Nov;47(3):162-6. doi: 10.1002/ajh.2830470303.
We examined the antithrombotic effect of recombinant human soluble thrombomodulin (rhs-TM) using an arteriovenous shunt thrombosis model and its influence on hemostasis in rats. Intravenous administration of rhs-TM (0.5-4 mg/kg) significantly inhibited thrombus formation and prolonged ex vivo activated partial thromboplastin time (APTT) in a dose-dependent manner. Thrombus formation was inhibited to the same extent in animals treated with heparin (25-200 U/kg) and in those treated with rhs-TM (0.5-4 mg/kg), but heparin had a much stronger effect on prolonging APTT. In the hemorrhagic study using the rat template bleeding time method, rhs-TM exhibited the prolongation of the bleeding time only at the highest effective dose (rhs-TM; 4 mg/kg) of the thrombosis experiments. Thus, rhs-TM exhibits the inhibitory effect on thrombus formation with less APTT prolongation in comparison with heparin and without significant pertubation of hemostasis.
我们使用动静脉分流血栓形成模型研究了重组人可溶性血栓调节蛋白(rhs-TM)的抗血栓作用及其对大鼠止血的影响。静脉注射rhs-TM(0.5-4mg/kg)以剂量依赖的方式显著抑制血栓形成并延长体外活化部分凝血活酶时间(APTT)。用肝素(25-200U/kg)治疗的动物和用rhs-TM(0.5-4mg/kg)治疗的动物的血栓形成受到相同程度的抑制,但肝素对延长APTT的作用要强得多。在使用大鼠模板出血时间法的出血研究中,rhs-TM仅在血栓形成实验的最高有效剂量(rhs-TM;4mg/kg)时表现出出血时间延长。因此,与肝素相比,rhs-TM对血栓形成具有抑制作用,同时较少延长APTT,且对止血无明显干扰。