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天麻通过增强 GABA 能传递缓解戊四氮致痫大鼠颞叶癫痫发作严重程度和神经元兴奋性毒性。

Gastrodin alleviates seizure severity and neuronal excitotoxicities in the rat lithium-pilocarpine model of temporal lobe epilepsy via enhancing GABAergic transmission.

机构信息

Department of Neurology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung City, 42743, Taiwan.

Department of Research, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung City, 42743, Taiwan.

出版信息

J Ethnopharmacol. 2021 Apr 6;269:113751. doi: 10.1016/j.jep.2020.113751. Epub 2021 Jan 4.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Temporal lobe epilepsy remains one of the most drug-resistant focal epilepsy, leading to enormous healthcare burden. Among traditional herb medicine, some ingredients have the potential to treat seizure and alleviate the neuronal excitoxicity. The dried rhizome of Gastrodia elata Blume has been used to treat convulsive disorder, dizziness, dementia and migraine in eastern Asia.

AIM OF THE STUDY

To determine whether gastrodin, an active ingredient of Gastrodia elata Blume, can reduce lithium-pilocarpine induced seizure severity and neuronal excitotoxicity and explore the underlying mechanism.

MATERIALS AND METHODS

We divided the Sprague-Dawley rats into an experimental group (gastrodin group) and a control group (Dimethyl sulfoxide, vehicle group) and performed the behavioral analysis and electroencephalography to determine the effect of gastrodin on the seizure severity induced by lithium-pilocarpine injection. Nissl-stained histopathology elucidated the degree of rat hippocampal neuronal damage as markers of acute and subacute neuronal excitotoxicity. Besides, the Western blotting of dissected hippocampus was carried out to demonstrate the protein expression involving GABAergic transmission and metabolic pathway.

RESULTS

Gastrodin reduced the acute seizure severity in lithium-pilocarpine-induced seizure model. In electroencephalography recording, gastrodin exerted inhibitory action on epileptiform discharge. Compared with control group, gastrodin exhibited neuroprotective effect against seizure related hippocampal neuronal damage at acute and subacute stages. The Western blotting showed that gastrodin reversed the degradation of GABA receptor after pilocarpine-induced seizures.

CONCLUSIONS

In the experimental seizure model, gastrodin showed anti-seizure and neuroprotective abilities. Enhancing the expression of GABA receptor plays an important role in its antiepileptic mechanism. The results offer a new insight of developing new antiepileptic drugs from traditional Chinese medicine.

摘要

民族药理学相关性

颞叶癫痫仍然是最具耐药性的局灶性癫痫之一,给医疗保健带来了巨大负担。在传统草药医学中,有些成分具有治疗癫痫和减轻神经元兴奋毒性的潜力。东亚地区一直将天麻的干燥根茎用于治疗惊厥、头晕、痴呆和偏头痛。

研究目的

确定天麻素(天麻的一种活性成分)是否可以减轻锂-匹罗卡品诱导的癫痫发作严重程度和神经元兴奋毒性,并探讨其潜在机制。

材料和方法

我们将 Sprague-Dawley 大鼠分为实验组(天麻素组)和对照组(二甲基亚砜,溶剂组),并进行行为分析和脑电图以确定天麻素对锂-匹罗卡品注射引起的癫痫发作严重程度的影响。尼氏染色组织病理学阐明了海马神经元损伤的程度,作为急性和亚急性神经元兴奋毒性的标志物。此外,还对分离的海马进行了 Western 印迹分析,以展示涉及 GABA 能传递和代谢途径的蛋白质表达。

结果

天麻素减轻了锂-匹罗卡品诱导的癫痫发作模型中的急性癫痫发作严重程度。在脑电图记录中,天麻素对癫痫样放电具有抑制作用。与对照组相比,天麻素在急性和亚急性阶段对与癫痫相关的海马神经元损伤表现出神经保护作用。Western 印迹显示,天麻素逆转了匹罗卡品诱导的癫痫后 GABA 受体的降解。

结论

在实验性癫痫模型中,天麻素表现出抗癫痫和神经保护作用。增强 GABA 受体的表达在其抗癫痫机制中起着重要作用。研究结果为从中药开发新型抗癫痫药物提供了新的思路。

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