依达拉奉对脑缺血再灌注损伤大鼠脑组织Fas及细胞凋亡的影响

目的观察依达拉奉对脑缺血再灌注损伤大鼠脑组织Fas及细胞凋亡的影响。方法24只雄性SD大鼠随机分为三组：假手术组（SH组）、缺血再灌注组（IR组）、依达拉奉治疗组（EDA组）,每组8只。IR组和EDA组线栓法制备脑缺血再灌注模型;SH组栓线只进入颈外动脉。EDA组于再灌注前30min和再灌注12h经腹腔注射依达拉奉3mg/kg,SH组和IR组在相同时间点注射等容量生理盐水。再灌注24h取血清测超氧化物歧化酶（SOD）活力、丙二醛（MDA）含量;取脑组织检测缺血半暗带Fas的表达及细胞凋亡情况;于再灌注3h和24h,参照Zealonga五级神经功能缺损评分标准评价神经功能损伤情况。结果与SH组比较,IR组和EDA组再灌注24h血清SOD活力降低（P〈0.01）,IR组SOD活力低于EDA组（P〈0.01）。与SH组比较,IR组和EDA组再灌注24h时血清MDA含量升高（P〈0.01）;IR组MDA含量高于EDA组（P〈0.05）。SH组脑组织无或仅有少量细胞Fas表达呈阳性,IR组与EDA组缺血半暗带均有大量Fas表达;EDA组平均灰度值较IR组大（P〈0.01）。SH组脑组织仅有少量凋亡细胞,IR组与EDA组缺血半暗带可见大量凋亡神经细胞;EDA组凋亡细胞数较IR组少（P〈0.01）。SH组各时点无神经损伤症状,再灌注3h,IR组与EDA组大鼠神经功能损伤差异无显著性（P〉0.05）;再灌注24h,与IR组比较EDA组大鼠神经功能损伤减轻（P〈0.05）。结论脑缺血再灌注后,大鼠血清SOD活力降低、MDA含量升高、大脑皮层半暗带Fas表达及凋亡细胞数明显增多。依达拉奉可保护SOD活力,降低MDA含量,减少缺血再灌注大脑皮层半暗带Fas的表达及细胞凋亡,从而减轻神经功能损伤,对脑缺血再灌注损伤具有一定的保护作用。

Effect of edaravone on the expression of Fas and neuron apoptosis after cerebral ischemia-reperfusion injury in rats

Objective To investigate the neuroprotective effects of edaravone on cerebral damage induced by cerebral ischemia-reperfusion injury in rats. Methods Twenty-four male SD rats weighing 280-300g were randomly divided into three group which were the sham operation group （SH, n=8）, the ischemia-reperfusion group （IR, n=8）, and the trial group of edaravone （EDA, n=8）. In group IR and group EDA the rats were subjected to cerebral ischemia-reperfusion injury by thread embolism of middle cerebral artery for 2 h ischemia followed by 24 h reperfusion, in group SH the rats were operated and nylon suture were just put into external carotid artery. At thirty minutes before reperfusion and 12 h after reperfusion, edaravone （3 mg/kg） was administered to the rats of group EDA and norreal saline to group SH and group IR by intraperitoneal injection. After the reperfusion period of 24 h, the rats were sacrificed and the changes of serum malondialdehyde （MDA）, superoxide dismutase （SOD） as well as the expression of Fas and cell apoptosis in rat brain were observed. At the time of 3 h and 24 h after reperfusion, the neurological deficit score （NDS） was assessed. Results SOD activity significantly decreased in group EDA and group IR than group SH at 24 h after reperfusion, but SOD
activity significantly increased in group EDA compared with that in group IR （P〈0. 01）. MDA concentration in group EDA and group IR significantly increased than that in group SH at 24 h after reperfusion, MDA concentration in group IR obviously increased than group EDA （P〈0. 05）. The mean gradation of Fas in group EDA significantly increased than group IR （P〈0. 01）. TUNEL positive cells in group EDA obviously decreased than those in group IR （P〈0. 01）. At 3h after reperfusion, the NDS increased in group IR and group EDA compared with that in group SH and there were no difference in them. At 24 h after reperfusion, the NDS in group IR and group EDA obviously decreased, but the NDS in group EDA decreased t