依达拉奉对脑缺血大鼠重组组织型纤溶酶原激活剂溶栓后金属蛋白酶9表达的影响

Effect of rt-PA and Edaravone on the Expression of MMP-9 in Rats with Cerebral Ischemic Injury

目的观察依达拉奉对脑缺血大鼠重组组织型纤溶酶原激活剂（rt-PA）溶栓后基质金属蛋白酶9（MMP-9）的表达的影响,探讨依达拉奉对溶栓后脑组织的保护作用。方法采用大鼠自体血栓栓塞大脑中动脉闭塞（MCAO）模型,112只入选的SD大鼠分为假手术组（A组）、模型对照组（B组）、rt-PA溶栓组（C组）及依达拉奉联合rt-PA组（D组）,每组大鼠28只。应用红四氮唑染色观察各组大鼠脑梗死的体积百分比,同时进行神经功能缺损程度评分（SSS）,免疫组织化学方法检测各组大鼠脑MMP-9的表达及相应病理学检查。结果与模型对照组比较,rt-PA溶栓组比较,脑梗死体积百分比及SSS评分降低,MMP-9表达明显降低（P〈0.05～0.01）。与rt-PA溶栓组比较,依达拉奉联合rt-PA组脑梗死体积百分比及SSS评分降低,MMP-9表达明显降低（P〈0.05～0.01）。结论依达拉奉可有效的抑制rt-PA溶栓后的大鼠脑梗死范围增大,抑制MMP-9的过度表达,从而减轻对血脑屏障的破坏,进而可能延长溶栓治疗的时间窗,进一步阻止脑梗死体积扩大和改善神经功能。

Objective To study the protection mechanism of Edaravone following thrombolytic therapy in rt-PA against focal cerebral ischemia reperfusion injury in rats. Methods A rat model of embolic stroke was set up in each of the rats of groups embolizing the middle cerebral artery by thrombus（MCAO）. 112 SD rats were randomly divided into 4 groups： A the sham operation group（n=28）, B the model group without treatment（n=28）, C rt-PA group（n=28）, D combined edaravone with rt-PA group （n=28）. The infarction volume of brain was investigated by 2, 3, 5-Triphenyl tetrazolium chloride （TTC） coloring and the neurologic deficit scores of rats were documented. The histological morphological damage of brain was investigated by hematoxylin-eosin （HE） staining. The expression of matrix MMP-9 in brain tissue was observed by immunohistochemistry method. Results Contrast to group B, the volume of brain infarction in rats of group C was obviously smaller （P〈0.01）, the score of neurologic impairment assessment was lower（P〈0.05）, the expression of MMP-9 was obviously decreased（P〈0.05）; Contrast to group C, the volume of brain infarction in rats of group D was obviously smaller（P〈0.01）, the score of neurologic impairment assessment was lower（P〈0.05）, the expression of MMP-9 was obviously decreased（P〈0.05）. Conclusion It is assumed that combination Edaravone with rt-PA thrombolysis may inhibit MMP-9 expression, then relieve the damage of reperfusion to BBB, and may prolong the thrombolytic therapeutic time window. Our study suggest that Edaravone could be potent neuroprotector against brain ischemia injury.