新型水蛭肽嵌合蛋白治疗脑出血后脑水肿的实验研究

Experimental Study of Hirudin Peptide Chimeric Protein for Treating Brain Edema after Intracerebral Hemorrhage

目的探讨新型基因工程药物水蛭肽嵌合蛋白(TNHH)对大鼠脑出血后脑水肿的治疗作用及其机制。方法将96只成年雄性SD大鼠随机分为假手术组、脑出血模型组、TNHH组,以自体血注入大鼠尾状核方法建立脑出血模型,假手术组只进针不注血。TNHH组静脉注射TNHH(2mg/kg),分别于造模前30min及造模后每12h给药1次。于6,24,72,168h时分别用Longa标准测定神经功能缺损,干、湿重法检测脑含水量,分光光度法测定脑血肿周围脑组织髓过氧化物酶(MPO)活性。结果与假手术组相比,脑出血模型组大鼠神经功能缺损评分、脑含水量、MPO活性均显著增高(P<0.05或P<0.01);与脑出血模型组相比,TNHH组大鼠神经功能缺损评分、脑含水量、MPO活性显著下降(P<0.05或P<0.01)。结论 TNHH对大鼠脑出血后脑水肿有治疗作用,其机制可能与抑制凝血酶活性、降低中性粒细胞浸润有关。

Objective To investigate the therapeutic effect of hirudin peptide chimeric protein （TNHH） on cerebral edema in rats following intracerebral hemorrhage（ICH） and its mechanism. Methods In this series, 96 Spragne-Dawley rats were divided into three groups at random（n=32 in each group）： sham operative group, ICH model group and TNHH therapy group. ICH model was induced by infusion of autologous whole blood into the rat caudate nucleus. The rats in shamoperative group were treated the same procedure as above, but no blood injected. The rats in TNHH therapy group were treated with TNHH （2 mg/kg） by intravenous injection at 30 min before operation and once per 12 h after operation. These rats were killed at 6, 24, 72, 168 h after neurologic impairment test with Longa criteria. Brain water content was measured by dry-wet weight method. The myeloperoxidase （MPO） activity was determined by spectrophotometry. Results Compared with the sham operative group, the neurologic impairment score, brain water content, the MPO activity in brain tissues were obviously higher in ICH model group（ P 〈 0. 05）. Compared with ICH model group, the neurologic impairment score, brain water content, the MPO activity in brain tissues were significantly decreased in TNHH therapy group（ P 〈 0. 05）. Conclusion TNHH has the evident treatment effect on brain edema after intracerebral hemorrhage through inhibiting thrombin and decreasing neutrophil infiltration in the vicinity of hematoma.