小檗碱治疗大鼠癫痫作用机理的研究

摘要

Objective To explore the effects and mechanism of berberine in the treatment of epilepsy in rats from oxidative stress and apoptosis.Methods Pilocarpine was used to establish rat epilepsy model.A berberine group (group B) was administrated with 25 or 50 mg/(kg·d) by gavage.Three days after modeling,the contents of multiple cytokines,enzyme,reactive oxygen species (ROS) and glutathione (GSH) in the hippocampus were inspected;10 days after modeling,the duration and frequency of epileptic episodes (≥ Level 4) in rats were observed by video recording;after 10 consecutive days of observation,NeuN dyeing was applied to determine the loss of neurons on the hippocampus.Results (1) the episode duration and frequency in group B-50 were significantly shorter or lower than those in group B-25(P ＜ 0.05),and the episode duration and frequency in the two groups were much shorter or lower than those in the epilepsy group (group S) (P ＜ 0.05).(2) Compared with group S,the ROS,HO-1,caspase3 and CTSD in the control group (group N) were significantly lower (P ＜ 0.05),but GSH,CAT and Nrf2 were much higher (P ＜ 0.05);the GSH,CAT and Nrf2 in group B-25 were significantly higher (P ＜ 0.05),but the caspase3 was much lower (P ＜ 0.05);the GSH,CAT,Nrf2 and HO-1 in group B-50 were significantly higher (P ＜ 0.05),but ROS,caspase3 and CTSD were much lower (P ＜ 0.05).(3) Compared with group B-25,the Nrf2 and HO-1 in group B-50 were significantly higher (P ＜ 0.05),but the caspase3 was much lower (P ＜ 0.05).(4)20 days after modeling,the number of neuron in area CA3 in group S was significantly lower (P ＜ 0.05);the number of neuron in the same area in group B-50 was higher than that in group B-25,but there was no significant difference(P ＞ 0.05).Conclusion Berberine can reduce the duration and frequency of epileptic seizures by inhibiting oxidative stress and apoptosis to reduce the loss of hippocampal neurons.%目的 从氧化应激和细胞凋亡两方面探索小檗碱对大鼠癫痫发作的影响及作用机理.方法 匹鲁卡品诱导建立大鼠癫痫模型,小檗碱组(B组)分别给予[25或50 mg/(kg· d)]小檗碱灌胃.建模后3d,检测海马内多种细胞因子、酶、活性氧(ROS)及谷胱甘肽(GSH)的含量;建模后10d,录像观察大鼠癫瘸发作(≥4级)的时间、频率;连续观察10 d后,使用NeuN染色检测海马内神经元的丢失情况.结果 (1)发作时间和频率,B-50组显著低于B-25组(P＜0.05),且两组均显著低于癫痫组(S组)(P＜0.05).(2)与S组相比,对照组(N组)ROS、HO-1、caspase3、CTSD显著降低(P＜0.05),GSH、CAT、Nrf2显著升高(P ＜0.05);B-25组GSH、CAT、Nrf2显著升高(P＜0.05),caspase3显著降低(P＜ 0.05);B-50组GSH、CAT、Nrf2、HO-1显著升高(P＜0.05),ROS、caspase3、CTSD显著降低(P＜0.05).(3)与B-25组相比,B-50组Nrf2、HO-1显著升高(P＜0.05),caspase3显著降低(P＜0.05).(4)建模后20 d,S组CA3区神经元数目较其他3组显著降低(P＜0.05),B-50组高于B-25组,但两组间无显著差异(P＞0.05).结论 小檗碱通过抑制氧化应激反应和细胞凋亡来减少海马神经元的丢失,进而降低癫痫发作的时间和频率.