水蛭素和重组链激酶联合应用于脑出血血肿腔中的实验研究

Research on the effect of hirudin combineded with recombinant streptokinase administrated in the cavity of intracerebral hemorrhage

目的 研究水蛭素和重组链激酶联合应用于脑内出血 (ICH)血肿腔中对血肿周围脑组织的影响。方法 72只SD雄性大鼠制成ICH模型 ,随机分为对照组、重组链激酶组、水蛭素 +重组链激酶组 (联合组 ) ,各组分别在ICH后 8h、16h、2 4h、4 8h向血肿腔中注入生理盐水、重组链激酶、或重组链激酶加水蛭素。ICH后 72h处死大鼠 ,观察脑组织中的含水量、Na+ 、K+ 以及血脑屏障通透性的变化。结果 在ICH后 8h、16h、2 4h、4 8h应用重组链激酶 ,可引起脑组织含水量增加以及Na+ 、K+ 的变化 (P <0 .0 5 ) ,在ICH后 8h重组链激酶组 ,脑组织中伊文思蓝 (Evansblue,EB)含量明显升高 (P <0 .0 5 )。联合组与重组链激酶组比较脑组织的含水量在 8h、16h、2 4h、4 8h明显降低 (P <0 .0 5 ) ,脑组织中EB含量在 8h、16h、2 4h、4 8h也明显降低 (P <0 .0 5 )。结论 ICH血肿腔内单独应用重组链激酶可加重ICH血肿周围脑组织的损伤 ,联合应用水蛭素不但可防治重组链激酶溶化血块时对脑组织的损伤 。

Objective To investigate the effect of hirudin combineded with recombinant streptokinase (r-sk) on the perihematomal brain tissue of intracerebral hemorrhage (ICH).Methods 72 adult male SD rat models of intracerebral hemorrhage were divided randomly to 3 groups: contrast, r-sk and combination. The hematomal cavity was injected with normal saline (NS), r-sk, hirudin plus r-sk at the 8 h, 16 h, 24 h, 48 h after ICH. The rats were decapitated at 72 h after ICH. The brain water content and K +, Na + content and blood brain barrier (BBB) permeability were measured.Results In r-sk groups, the water content of the perihematomal tissue increased at the 8 h, 16 h, 24 h, 48 h after ICH; The K +, Na + content changed obviously at 8 h, 16 h, 24 h, 48 h (P<0.05); The EB content increased obviously at 8 h (P<0.05). While in combination groups, the water content of the perihematomal tissue obviously decreased, especially at 8 h, 16 h, 24 h, 48 h compared to the r-sk groups(P<0.05). The EB content also decreased obviously at 8 h, 16 h, 24 h, 48 h compared to the r-sk groups(P<0.05).Conclusion Using recombinant streptokinase in the hematomal cavity will deteriorate the perihematomal brain tissue injury after ICH, while r-sk plus hirudin administrated in the hematomal cavity will not only prevent the damage produced by the using of plasminogen activator for lysis of hematoma, but also can reduce the damage to the brain tissue produced by toxin released from hematoma itself.