依达拉奉对小鼠急性脑缺血-再灌注损伤的保护作用

Protective effect of edaravone on cerebral ischemia-reperfusion injury in mice

目的探讨依达拉奉对小鼠急性脑缺血-再灌注(I-R)损伤的保护作用及机制。方法健康雄性昆明小鼠126只随机分为3组。C组18只,为假手术组;制备大脑中动脉闭塞模型,于再灌注开始后每24小时经尾静脉注射依达拉奉(Y组,54只)或等体积生理盐水(NS组,54只);分别于再灌注12、24和72 h进行行为学评分、脑组织含水量、脑梗死体积、线粒体膜电位以及蛋白质、脂质和核酸氧化应激指标的测定。结果依达拉奉能够显著降低脑I-R后行为学评分、脑组织含水量及脑梗死体积;依达拉奉可改善缺血诱导的皮质及内囊区降低的线粒体膜电位,明显降低3-硝基酪氨酸,4-羟基壬烯酸和8-羟基脱氧鸟苷的水平。结论依达拉奉通过抑制蛋白质、脂质和核酸氧化应激保护小鼠脑I-R损伤。

Objective To study the protective effect of edaravone on cerebral ischemia-reperfusion（I-R） injury and its mechanism in mice.Methods A total of 126 male Kunming mice was randomly divided into three groups of C（sham operation,18 mice）,E（middle cerebral artery occlusion with edaravone injection per 24 hours during reperfusuin,54 mice）and NS（middle cerebral artery occlusion with saline injection instead of edaravone as in group Y,54 mice）.Groups of Y and NS were further divided into 12,24 and 72 hours subgroups according to the time of reperfusion.Behavior test,brain water content,cerebral infarct volume,mitochondria membrane potential and oxidative stress markers were determined at 12,24 and 72 hours during reperfusion.Results Compared to group NS,the mice in group Y were with significantly less modified Neurological Severity Score（mNSS）,brain edema and cerebral infarct size,higher mitochondrial membrane potential both in cerebral cortex and internal capsule,lower contents of 3-Nitro-L-tyrosine（3-NT）,4-hydroxy-2-nonenal（HNE） and 8-hydroxy-2′-deoxyguanosine（8-OHdG） at 12,24 and 72 hours during reperfusion.ConclusionEdaravone has a remarkable neuroprotective effect by inhibiting oxidative stress in mouse with cerebral I-R injury.