托吡酯、丙戊酸钠预防幼鼠慢性癫痫脑损伤的实验研究

A Research on Prophylaxis of Brain Damage in Epileptic Rats with Topiramate and Sodium Valproate

目的研究托吡醣、丙戊酸钠单药及联合用药对幼鼠慢性癫痫脑损伤的影响。方法将3～4周龄雄性Wistar大鼠60只随机分为5组,B、C、D、E组为慢性癫痫组,C、D、E组于戊四氮(PZT)腹腔注射后给予TPM 40 mg/kg、VPA 200mg/kg、TPM 40mg/kg+VPA 200mg/kg,A、B组给予等量的蒸馏水,连续用药2个月,观察癫痫发作后幼鼠的体重改变、行为学表现及海马组织病理形态学的变化检测血清神经元特异性烯醇化酶(NSE)水平,了解脑损伤的发生情况及药物的情况保护。结果①TPM使体重增长降低,VPA使体重增长增加;②TPM、VPA均使发作持续时间缩短(P<0.05),联合用药组使发作持续的时间长(P<0.05);③TPM组、VPA组的NSE水平降低显著(P<0.05);④TPM组、VPA组神经元的退行性变和胶质细胞的反应性增生较阳性组减少。TPM+VPA组神经元变性坏,胞浆浓缩,出现红色神经元。结论TPM、VPA单药均对癫痫脑损伤有保护作用,但2者联合可能削弱其单药的神经保护作用。

Objective To explore the prophylaxis of EP and the protection of seizure-induced cerebral damage in immature rats with topiramate（TPM）, sodium valproate（VPA） and the mixture of the two. Methods Sixty 3 or 4 week-old male Wistar rats were randomly divided into 5 groups evenly. The groups （Groups B-E ） were rat models of epilepsy, induced by pentylenetetrazol （PTZ）. The rats in three experimental groups were adminstered intragastrically with TPM 40 mg/ （kg·d）, VPA 200 mg/（kg·d） and TPM 40 mg/（kg·d） ＋ VPA 200 mg/（kg·d）, the two control groups（Groups A and B ）with the equal amount the changes of body weight, the behavior of the of distilled water. After 2-month administration, rats were observed, the ultrastructural change of the hippocampus were oberved under the electron microscope, and the levels of serum neuron-specific enolase（NSE） of blood serum was detected. Result （1） TPM reduced the body weight gain of rat, VPA raised the body weight gain of rat. （2） TPM and VPA delayed the latent period, the duration time was shorter （P〈0.05）, but the duration time in group E was longer（P〈 0. 05）. （3） The level of NSE in the group TPM and VPA was lozzer （P〈0.05）, but it was not significant low in group TPM ＋ VPA （P〉0.05）. （4） The damaged neurorz in TPM group and VPA group had lessened, but the group TPM ＋ VPA had improved little. Conclusions Continuous adminstration of the two antiepilepsy drugs was found to be effective in preventing seizure and protecting brain damage, but the mixture of the two drugs may weaken this effect.