叶酸对托吡酯幼鼠脑神经元保护作用的影响

Influence of folic acid on the protective role of topiramate against neuronal damage in immature rats

目的探讨叶酸(FA)对托吡酯(TPM)幼鼠脑神经元保护作用的影响。方法将3周龄雄性Wistar大鼠随机分为4组。阳性对照组、TPM组和FA+TPM组先行戊四氮(PTZ)腹腔注射制造幼鼠慢性癫癇模型,再分别给予等量蒸馏水、TPM40mg/(kg·d)和FA5mg/(kg·d)+TPM40mg/(kg·d)灌胃;阴性对照组先行生理盐水腹腔注射,再给予等量的蒸馏水灌胃。连续用药2个月,观察大鼠行为、血清神经元特异性烯醇化酶(NSE)及海马区病理改变。结果TPM组和FA+TPM组大鼠惊厥发作次数、血清NSE水平及海马区神经元死亡程度明显轻于阳性对照组。FA+TPM组与TPM组血清NSE水平比较,差异无统计学意义;FA+TPM组海马区坏死神经元百分比明显低于TPM组。结论FA可加强TPM的幼鼠脑神经元保护作用。

Objectives To explore the influence of folic acid （FA） on the protective role of topiramate （TPM） against neuronal damage in immature rats. Methods Pentylenetetrazol（PTZ）-induced kindling in rats was used to establish rat epilepsy models. Forty-eight 3-week-old male Wistar rats were randomly assigned into 4 groups with 12 rats each： two treatment groups with TPM 40 mg/（kg·d） or FA 5 mg/（kg·d） ＋ TPM 40 mg/（kg·d）, one positive control groups （with PTZ induction）, one negative control group （without PTZ induction） with the equal amount of distilled water administration. Treatment continued two months. Behaviors of the rats were recorded, the levels of serum neuronspecific enolase （NSE） were measured by ELISA and the pathological changes in hippocampus were observed. Results The frequency of seizure, the levels of NSE and degree of neuron death in the two treatment groups were higher than those in the negative control group, but significantly lower than those in the positive control group. There was no statistical difference in the level of NSE between FA ＋ TPM group and TPM group. However, the percentage of neuron death in FA ＋ TPM group was significant lower than that in TPM group. Conclusions Folic acid may strengthen the protective effect of TPM against neuronal damage in immature rats.