局部应用重组水蛭素治疗脑出血后脑水肿的实验研究

Experimental study on local administration of recombinant hirudin for brain edemain rat models of intracerebral hemorrhage

目的探讨局部应用凝血酶特异性抑制剂(重组水蛭素)治疗脑出血后保护机制。方法成年雄性SD大鼠随机分为生理盐水组、脑出血组和水蛭素组(出血后3 h)。以50μl自体血注入大鼠尾状核方法建立脑出血模型,应用干-湿重法观察脑水肿变化,前肢放置实验观察行为学。每组每时相点(1、2、3、7、14、28天)各6只大鼠。结果脑出血组和水蛭素组脑含水量与生理盐水组在24 h、48 h、72 h比较P<0．05,7天时各组间无明显差异(P>0．05)；脑出血组大鼠前肢放置实验结果与生理盐水组比较(P<0．05),水蛭素组与脑出血组比较P<0．05。结论脑出血后24-48 h水肿达高峰；重组水蛭素可明显减轻脑水肿,同时可以改善脑出血后的神经功能缺损。

Objective To investigate the protective effect and mechanism of local recombinant hirudin （thrombin inhibitor） on experimental intracerebral hemorrhage （ICH） in rats. Methods SD rats were randomly divided into saline control group, ICH control group and treatment group （with hirudin applied 3 hours after ICH）. ICH model was established by injecting 50μl of autologous blood into the caudate nucleus. At 6 time points （1 d,2 d,3 d,7 d, 14 d and 28 d after ICH）, the behavioral assessments by Vibrassae - stimulated forelimb placing and the estimate of brain edema by dry - wet weighing method, were performed. Results Significant differences in cerebral edema were found between saline and ICH controls and between ICH and treatment groups at 1 d, 2 d and 3 d （ P 〈 0.05）, but no such differences among the three groups were noticed any more at 7 d and 14 d. Behavioral assessments at all of the 6 time points, showed the scores of the treatment group were superior to those of the ICH control group, but still inferior to that of the saline control. Conclusion The brain edema reaches its peak 48 h after ICH. The edema and neurological deficits can be obviously improved when recombinant hirudin is applied early after ICH, suggesting that it is theoretically rational to use local recombinant hirudin for ICH. ,