阿魏酸通过抗凋亡途径改善戊四氮诱导的癫痫鼠的脑神经损伤

Amelioration of pentylenetetrazole-induced nerve injury in epileptic rats by ferulic acid via anti-apoptosis pathway

目的探讨阿魏酸(ferulic acid,FA)对戊四氮诱导的癫痫大鼠的脑神经保护作用及其机制。方法将60只雄性Wistar大鼠分成5组:生理盐水组、戊四氮组(注射戊四氮造癫痫鼠模型)、高剂量阿魏酸组、中剂量阿魏酸组和低剂量阿魏酸组。用Racine评分评估癫痫发作的严重程度。通过Hochest 33258染色法检测细胞凋亡率,评价阿魏酸对癫痫大鼠脑神经细胞凋亡的影响;通过Western印迹分析脑Bcl-2和Bax中的表达水平。结果与戊四氮组相比,阿魏酸治疗组中Racine评分显著降低,癫痫发作持续时间明显缩短,而癫痫发作潜伏期显著延长(P<0.01);与戊四氮组比较,阿魏酸降低了癫痫鼠的海马神经元细胞凋亡率(P<0.01);与戊四氮组相比,阿魏酸治疗组海马中Bcl-2的表达升高,Bax的表达明显下调(P<0.01)。结论阿魏酸可减轻癫痫发作,阿魏酸对戊四氮诱导的大鼠癫痫模型脑损伤具有神经保护作用,其机制可能是通过抗凋亡作用。

Objective To investigate the neuroprotective mechanism of ferulic acid(FA)on pentylenetetrazol-induced epilepsy rats.Methods Sixty male Wistar rats were randomly divided into normal saline group,pentylenetetrazol group,high,medium and low dose FA groups.The severity of seizures was assessed using the Racine score.Apoptosis was detected by Hochest 33258 staining,and the effect of FA on neuronal apoptosis in epileptic rats was evaluated.The expression levels of Bcl-2 and Bax in brain were analyzed by Western blot.Results The Racine score was significantly lower in FA-treated group;seizure duration was significantly shorter,and the seizure latency was significantly longer when compared with those in pentylenetetrazol group(P<0.01).Compared with that in pentylenetetrazol group,apoptosis rate of hippocampal neurons in epileptic rats was decreased in FA-treated group(P<0.01).Compared with those in pentylenetetrazol group,the expression of Bcl-2 was increased and the expression of Bax was significantly down-regulated in hippocampus of FA-treated group(P<0.01).Conclusions FA can reduce seizures.It has neuronprotective effect on brain damage of pentylenetetrazoleinduced epilepsy rat,and its mechanism may be related with anti-apoptotic effect.