依达拉奉对大鼠脑梗死溶栓治疗后MMP-9表达的影响

Effect of edaravone on the matrix metal-oproteinase-9(MMP-9) expression after thrombolytic therapy for cerebral ischemia in rats

目的研究依达拉奉对大鼠脑梗死溶栓治疗后脑组织中MMP-9表达及血脑屏障的影响,探讨依达拉奉对脑梗死溶栓治疗后再灌注损伤的保护机制。方法采用SD大鼠自体血栓栓塞法制备大脑中动脉闭塞模型,并将SD大鼠随机分为假手术组、尿激酶溶栓治疗组(UK)、尿激酶+依达拉奉治疗组(UK+ED),12h后分别以免疫组织化学法和比色法对SD大鼠脑组织中MMP-9表达水平和伊文思蓝含量进行测定。结果与尿激酶溶栓治疗组相比,尿激酶+依达拉奉组SD大鼠缺血侧脑组织MMP-9表达水平和EB含量均显著降低,差异具有统计学意义(P值均<0.01)。结论依达拉奉可能通过下调MMP-9表达,减轻血脑屏障的破坏,减轻溶栓后脑缺血再灌注损伤。

Objective To explore the neuroprotective mechanism of edaravone after thrombolytic therapy by studying the effect of edaravone on the matrix metal-oproteinase-9（MMP-9） expression,blood-brain barrier（BBB） following thrombolytic therapy in urokinase after focal cerebral ischemia in rats.Methods The middle cerebral artery（MCA） of Sprague-Dawley rat was occluded by autologous blood clots.Rats were randomly assigned to sham-operated group（sham group）,urokinase therapy group（UK group） and urokinase with edaravone group（UK＋ED group）.The expression of matrix MMP-9 in brain tissue was observed by immunohistochemistry.The permeability of blood-brain barrier was evaluated based on leakage of Evans blue and the content of EB in the brain tissue was measured by spectrophotometry.Results Contrast to UK group,the combination of UK and ED significantly decreased MMP-9 expression in the side of ischemia brain（P0.01）.Contrast to UK group,the combination of UK and ED significantly reduced EB content in the side of ischemia brain（P0.01）.Conclusion It is assumed that edaravone may inhibit MMP-9 expression,then relieve the damage of reperfusion to BBB,and may prolong the thrombolytic therapeutic time window.