苯妥英对局灶性脑缺血——再灌注后脑组织自由基含量的影响

Experimental research of protective effect of phenytoin in cerebral ischemia-reperfusion injury of rats

目的观察大鼠局灶性脑缺血-再灌注后脑组织自由基的变化及苯妥英(PHT)对其改善的影响,并探讨其保护作用机制。方法将雄性成年Wistar大鼠随机分为4组:即假手术组、缺血-再灌注组、PHT低剂量治疗组和PHT高剂量治疗组。采用线栓法制成大脑中动脉闭塞模型,每组均于手术后6h、12h、24h三个时间点测定脑组织超氧化物歧化酶(SOD)活力和丙二醛(MDA)水平的改变。结果缺血-再灌注组各时点SOD活力显著低于假手术组相应时点SOD活力(P<0.05),PHT低剂量治疗组和高剂量治疗组SOD活力明显高于缺血-再灌注组各时点SOD活力(P<0.05),PHT高剂量治疗组各时点SOD活力又明显高于低剂量治疗组,且具有显著性差异(P<0.05);缺血-再灌注组MDA水平显著高于假手术组相应时点MDA水平(P<0.05),PHT低剂量治疗组和高剂量治疗组MDA水平与缺血-再灌注组各相应时间点比较明显降低(P<0.05),PHT高剂量治疗组MDA水平与PHT低剂量治疗组各相应时间点比较明显降低(P<0.05)。结论脑缺血-再灌注后,缺血大鼠脑组织内的MDA的水平升高,SOD活力降低,说明自由基参与了脑缺血-再灌注损伤的病理生理过程。PHT可降低MDA的水平,增加SOD的活性,从而对脑缺血-再灌注损伤具有保护作用。

Objective To explore the protective effect of phenytoin on experimental cerebral ischemia-reperfusion injury of rats and its possible mechanism. Methods The model of focal brain ischemia was made by an intraluminal suture occulusion of the middle cerebral artery （ MCA ） in adult male wistar rats. 60 rats were randomly divided into four groups：sham-operation group, isehemia-reperfusion group and two treatment groups （phenytion 40mg/kg）. After operation 6h, 12h, 24h.the activities of SOD and the concentration of MDA group. Results The activities of SOD in ischemia-reperfusion group were lower than those （P〈0.05） at various stages,but in phenytion （20mg/kg,40mg/kg, i） treatment groups were higher reperfusion group （P〈0.05） and the 40mg/kg 20mg/kg or were measured in every in sham-operation group than those in ischemia-phenytion group was higher than those in 20mg/kg phenytion group （P〈 0.05）. The concentrations of MDA in ischemia-reperfusion group at various stage were higher than those in sham-operation group （ P〈0.05 ）,and in 40mg/kg phenytion groups were lower than those in （P〈0.05）, but in phenytion （20mg/kg, 40mg/kg） treatment group were lower than those in ischemia-reperfusion group. Conclusion The elevation of MDA levels, and the lovering of SOD activety might take part in the ischemia-reperfusion injury, and phenytion could have the effect of decrease the levels of MDA and increase the activities of SOD.