依达拉奉联合重组组织型纤溶酶原激活剂溶栓在大鼠脑卒中的应用

Application of thrombolysis with rt-PA and edaravone in treatment of embolic stroke in the rat

目的探讨联合依达拉奉对栓塞性脑卒中大鼠重组组织型纤溶酶原激活剂(rt-PA)静脉溶栓的效果。方法用血栓栓塞法制备大鼠大脑中动脉缺血模型。84只SD大鼠分为假手术组、模型组、rt-PA组和依达拉奉联合rt-PA组(联合组),每组21只。缺血3h后给予rt-PA(5mg/kg)溶栓治疗,联合组同时给予静脉注射依达拉奉(3mg/kg)溶栓后24h进行神经功能评分和脑梗死体积百分率分析,测定脑组织中伊文思蓝含量,用免疫组织化学方法评估溶栓后脑组织血脑屏障的变化。结果联合组梗死体积百分率低于rt-PA组(P<0.01),伊文思蓝含量低于rt-PA组(P<0.01),血脑屏障内皮屏障抗原表达较rt-PA组升高(P<0.05),微血管周围纤维蛋白原表达较rt-PA组减少(P<0.05)。结论依达拉奉和rt-PA联合治疗比单纯应用rt-PA溶栓治疗可进一步阻止脑梗死体积扩大和改善神经功能。

Objective To examine the efficacy of the free radical scavenger edaravone as an adjuvant for thrombolytic therapy with recombinant human tissue plasminogen activator（rt-PA） in a rat model of embolic stroke. Methods A rat model of embolic stroke was set up by embolizing the middle cerebral artery with thrombus. Eighty-four SD rats were randomly divided into 4 groups of 21 rats each： （1）the sham operation group, （2）the model group without treatment, （3）rt-PA group, （4）edaravone combined with rt-PA group. Each rat of group （4） was given IV injection of 5 mg/kg of rt-PA and 3 mg/kg of edaravone following 3 hours of ischemia. Twenty-four hours later neurological functional deficit score and the size of the brain infarct were assessed. The injury of BtAB after cerebral ischemia-reperfusion was assessed by determination of Evans blue（EB） content in brain tissue and immunohistochemistry method. Results After 24 hours of rt-PA thrombolysis, the sizes of brain infarcts in rats of group 4 were obviously smaller than those in rats of group 3 （P 〈0.01）. The EB content in brain tissue was significantly decreased in group 4 compared with group 3 （P 〈0.01）. The enodothelial barrier antigen（EBA） expression of BBB in group 4 was significangtly higher than that in group 3 （P d0.05）. The expression of fibrinogen around microvessels was significantly decreased in group 4 （P 〈0.05）. Conclusions Thrombolysis with combination of edaravone and rt-PA at 3 hours after ischemia significantly reduces infarct volume and improves neurological function.