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产自东亚钳蝎的钠通道调节剂的抗癫痫/促癫痫作用

肖倩¹, 张志平², 侯阳波¹, 瞿东晓¹, 汤乐乐^1,3, 陈黎佶¹, 李国毅^1,3, 吉永华², 陶杰^1,3, 朱宇丹^1,3,*

¹上海中医药大学附属普陀医院神经内科和中心实验室，上海 200333；²上海大学医学院和生命学院，上海 200444；³安徽医科大学普陀临床医学院，上海 200333

摘要

东亚钳蝎(Buthus martensii Karsch, BmK)是治疗癫痫的经典中药之一，已有上千年的历史。从BmK毒液中分离纯化的神经毒素被认为是作用于膜离子通道的主要活性成分。电压门控钠通道(voltage-gated sodium channels, VGSCs)在癫痫发生中起着重要的作用，使其成为重要的癫痫药物靶点。BmK的长链毒素由60~70个氨基酸残基组成，能特异性识别VGSCs，其中用于建立癫痫模型的α-样神经毒素与VGSC受体位点3结合，可诱发鼠类癫痫。而β或β-样神经毒素则与VGSC受体位点4结合，对癫痫模型有显著的抗惊厥作用。本综述旨在阐明BmK多肽作用于VGSCs的抗惊厥或惊厥作用，同时也为抗癫痫药物设计提供潜在的框架。

关键词： 东亚钳蝎; 毒素; 癫痫; 电压门控钠通道; 受体位点

Anti-epileptic/pro-epileptic effects of sodium channel modulators from Buthus martensii Karsch

XIAO Qian¹, ZHANG Zhi-Ping², HOU Yang-Bo¹, QU Dong-Xiao¹, TANG Le-Le^1,3, CHEN Li-Ji¹, LI Guo-Yi^1,3, JI Yong-Hua², TAO Jie^1,3, ZHU Yu-Dan^1,3,*

¹Department of Neurology and Central Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200333, China；²School of Medicine and School of Life Sciences, Shanghai University, Shanghai 200444, China；³Putuo Clinical Medical School, Anhui Medical University, Shanghai 200333, China

Abstract

The East Asian scorpion Buthus martensii Karsch (BmK) is one of the classical traditional Chinese medicines for treating epilepsy for over a thousand years. Neurotoxins purified from BmK venom are considered as the main active ingredients, acting on membrane ion channels. Voltage-gated sodium channels (VGSCs) play a crucial role in the occurrence of epilepsy, which make them become important drug targets for epilepsy. Long chain toxins of BmK, composed of 60–70 amino acid residues, could specifically recognize VGSCs. Among them, α-like neurotoxins, binding to the receptor site-3 of VGSC, induce epilepsy in rodents and can be used to establish seizure models. The β or β-like neurotoxins, binding to the receptor site-4 of VGSC, have significant anticonvulsant effects in epileptic models. This review aims to illuminate the anticonvulsant/convulsant effects of BmK polypeptides by acting on VGSCs, and provide potential frameworks for the anti-epileptic drug-design.

Key words: Buthus martensii Karsch; toxin; epilepsy; voltage-gated sodium channels; receptor site

收稿日期：　　录用日期：

通讯作者：朱宇丹　　E-mail: yudanzhu_putuo@foxmail.com

DOI: 10.13294/j.aps.2022.0064

引用本文：

肖倩, 张志平, 侯阳波, 瞿东晓, 汤乐乐, 陈黎佶, 李国毅, 吉永华, 陶杰, 朱宇丹. 产自东亚钳蝎的钠通道调节剂的抗癫痫/促癫痫作用[J]. 生理学报 2022; 74 (4): 621-632.

XIAO Qian, ZHANG Zhi-Ping, HOU Yang-Bo, QU Dong-Xiao, TANG Le-Le, CHEN Li-Ji, LI Guo-Yi, JI Yong-Hua, TAO Jie, ZHU Yu-Dan. Anti-epileptic/pro-epileptic effects of sodium channel modulators from Buthus martensii Karsch. Acta Physiol Sin 2022; 74 (4): 621-632