托吡酯对慢性癫痫幼鼠脑神经元损伤的影响

Effects of topiramate on neuronal damage in immature rats with chronic seizure

目的:探讨托吡酯(TPM)对幼鼠慢性癫痫发作引起的脑神经元损伤的影响。方法:将3周龄雄性Wistar大鼠随机分为5组。阳性对照组和TPM不同剂量治疗组先行戊四氮腹腔注射制造幼鼠慢性癫痫模型,再分别给予等量蒸馏水、TPM20、40、80mg/(kg·d)灌胃;阴性对照组则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。观察幼鼠行为、血清神经元特异性烯醇化酶(NSE)及海马区病理改变。结果:(1)阴性对照组幼鼠无惊厥发作;TPM治疗组与阳性对照组相比,幼鼠惊厥发作次数少、程度轻。(2)TPM治疗组幼鼠血清NSE值均高于阴性对照组而明显低于阳性对照组,且TPM剂量越高,血清NSE值越低。(3)阴性对照组幼鼠海马区未见神经元死亡;TPM治疗组幼鼠海马坏死神经元细胞数明显低于阳性对照组,且TPM剂量越高,坏死神经元细胞数越少,差异有显著性。结论:TPM对幼鼠慢性癫痫发作引起的脑神经元损伤具有保护作用,且其保护作用存在剂量效应,TPM80mg/(kg·d)保护作用最强。

Objective To investigate the effects of topiramate （TPM） on neuronal damage in immature rat with chronic seizure. Methods Wistar rats aged 3 weeks were randomly divided into 5 groups. The rats in 4 of the groups were injected intraabdominally with pentylenetetrazol （PTZ） to construct a murine model of epilepsy and then assigned to receive gastric infusion with either distilled water （positive control group） or TPM at a dose of 20 mg/kg, 40 mg/kg, or TPM 80 mg/kg （TPM groups） daily for 2 consecutive months. The rats in the remaining group received intraabdominal injection of normal saline and then gastric administration of distilled water （negative control group）. Behaviors of the rats were recorded. Levels of serum neuron-specific enolase （NSE） were measured by ELISA and the pathological changes in hippocampus were observed. Results （1） No seizure developed in the negative control group. Fewer frequencies of seizure occurred and the attack was less severe in the TPM groups than in the positive control group. （2） NSE levels in the TPM groups were higher than those in the negative control group but markedly lower than those in the positive control group with a reversed association with the dosage of TPM. （3） No neuronal death in hippocampus was observed in the negative control group. The number of dead neurons was significantly lower in the TPM groups than in the positive control group with a reversed relation with the dosage of TPM. Conclusion TPM plays a protective role in epilepsy-induced neuronal damage in a dose-dependent manner.