重组水蛭素抗家兔体外血栓形成作用的实验研究

Experimental study on ex vivo antithrombotic effect of r-hirudin in rabbits

关键词:  重组水蛭素  体外血栓形成  量效关系  时效关系

Key words:  r-hirudin  ex vivo thrombosis  dose-effect relationship  time-effect relationship

摘要:

研究国产重组水蛭素（r-hirudin，rH）对家兔体外血栓形成的对抗作用，为rH的新药开发提供实验研究资料。［方法］采用Chandler体外血栓形成模型，家兔iv rH前及iv后心脏采血，立即置于Chandler体外血栓形成仪中，测定体外血栓形成之栓长和血栓块干重，并与药前比较计算血栓形成抑制百分率。［结果］量效关系研究表明rH 1.0、0.5、0.25和0.125 mg·kg-1 iv后栓长抑制率分别为100%、96.37%、 36.83%和1.93%，血栓干重抑制率分别为100%、97.56%、45.05%和4.63%。时效关系研究表明rH 0.5 mg·kg-1 iv后5、15、30、60及120min对血栓栓长的抑制率分别为96.09%、93.94%、42.14%（P<0.01）和-2.47%、-5.34%（P>0.05），血栓干重抑制率分别为97.81%、96.03%、53.20%（P< 0.01）和0.59%、8.26%（P>0.05）。［结论］国产rH具有明显的体外抗血栓作用，且具有明显的量效和时效关系。并与国外同类权威产品Reludan作用强度一致

Abstract:

To study the inhibitory effect of r-hirudin(rH) made domestically on ex vivo thromosis in rabbits.［Methods］　Chandler ex vivo thrombosis model was utilized in this experiment. The blood samples were collected by cardiac puncture before and after iv administration, and then thrombotic length and dry weight were measured, inhibitory rates of thrombosis were calculated. ［Result］ The dose-effect relationship showed that the inhibitory rates of thrombosis were 100%，93.37%，36.83% and 1.93% based on thrombotic length，and 100%，97.56%，45.05% and 4.63% based on thrombotic dry weight at doses of 1.0，0.5，0.25 and 0.125 mg·kg-1 respectively; the time effect relationship showed that at 5，15，30，60 and 120 min post injection, the inhibitory rates were 96.09%，93.94%，42.14%（P<0.01）and -2.47%，-5.34%（P>0.05）on thrombotic length basis；and 97.81%，96.03%，53.20%（P<0.01）and 0.59%，8.62% （P>0.05）on dry werght basis respectively. ［Conclusion］ The domestic rH has potent ex vivo antithrombotic effect and shows good dose-and time-effect relationship, and exhibits the identical anthrombotic activity to Refludan, an authentic rH product made by Hoechst Company Germany