中药复方制剂熄风胶囊和卡马西平联合治疗对匹罗卡品癫痫大鼠海马电压门控性钠通道的影响

The effect of Xifeng Capsule combined with carbamazepine on hippocampal voltage-gated sodium channel of epilepsy rat models indused by Lithium-pilocarpine

关键词:  电压门控性钠通道  熄风胶囊  卡马西平  癫痫

Key words:  voltage-gated sodium channel  Xifeng Capsule  carbamazepin  epilepsy

摘要:

[目的] 观察熄风胶囊和卡马西平（CBZ）联合氯化锂-匹罗卡品对SD大鼠癫痫模型海马神经元电压门控性钠通道（VGSC）的影响。[方法] 将110只SD大鼠随机选出20只作为空白对照组，其余大鼠造模成功后再先后随机选出80只，分为模型对照组、熄风胶囊治疗组（熄风组）、熄风胶囊和CBZ治疗组（熄卡组）和CBZ治疗组（CBZ组）。通过免疫组化法检测VGSC的表达和全细胞膜片钳检测其电生理功能。[结果] 1）癫痫大鼠出现反复自发性发作，熄卡组发作次数低于熄风组和CBZ组。2）VGSC的表达：在CA3区，各治疗组VGSC的表达水平较模型对照组均下调，熄卡组明显低于熄风组和CBZ组。3）VGSC电生理功能：治疗组的峰值电流较模型对照组显著下降，其中熄卡组较熄风组和CBZ组明显；治疗组的半数稳态激活电压上升，但组间无差异；治疗组的半数稳态失活电压下降，其中熄卡组与熄风组相比有差异；治疗组的失活后恢复时间常数明显延长，其中熄卡组与熄风组相比有差异。[结论] 熄风胶囊和CBZ具有协同抗痫作用，优于单药治疗的主要药理机制是减少VGSC峰值电流。

Abstract:

[Objective] To observe the effects of Xifeng Capsule combined with carbamazepine (CBZ) on voltage-gated sodium channels (VGSC) in hippocampal neurons of epileptic SD rats induced by lithium chlorine-pilocapine.[Methods] The 20 SD rats were randomly selected from 110 SD rats as blank control group,and 80 rats were randomly selected after successful modeling,which were divided into model control group,Xifeng Capsule treatment group,Xifeng Capsule combined with CBZ treatment group,and CBZ treatment group.The expression of VGSC was detected by immunohistochemistry and its electrophysiological function was detected by whole cell patch clamp.[Results] 1) Recurrent spontaneous seizures occurred in the epileptic rats,and the frequency of seizures in the Xifeng Capsule combined with CBZ group was lower than that in the Xifeng Capsule treatment group and the CBZ group.2) Expression of VGSC:the expression level of VGSC in all treatment groups was down-regulated in CA3 region compared with that in model control group,and the expression level of VGSC in Xifeng Capsule combined with CBZ group was significantly lower than that in wind quenching group and CBZ group.3) Electrophysiological function of VGSC:compared with the model control group,the peak current in the treatment group decreased significantly,especially in the card extinguishing group compared with the Xifeng Capsule treatment group and CBZ group.The half steady-state activation voltage in the treatment group increased,but there was no difference between the groups.The 50% steady-state inactivation voltage of the treatment group decreased,and there was a difference between the Xifeng Capsule combined with CBZ group and the Xifeng Capsule treatment group.After inactivation,the recovery time constant of the treatment group was significantly prolonged,and there was a difference between the Xifeng Capsule combined with CBZ group and the Xifeng Capsule treatment group.[Conclusion] Xifeng Capsule and CBZ have synergistic antiepileptic effect.The main pharmacological mechanism superior to monotherapy is to reduce peak VGSC current.