Chaihu-Longgu-Muli decoction relieves epileptic symptoms by improving autophagy in hippocampal neurons
Chaihu-Longgu-Muli decoction relieves epileptic symptoms by improving autophagy in hippocampal neurons
复制标题
柴胡龙骨牡蛎汤通过改善海马神经元自噬缓解癫痫症状
DOI：
10.1016/j.jep.2020.112990
复制
发表时间：
2020-09-15
影响因子：
5.4
通讯作者：
Huang，Hui-yong
中科院分区：
文献类型：
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作者：
Yang，Ping;Qin，You;Huang，Hui-yong
柴胡龙骨木里汤（CLMD）是一种著名的古老中药方剂，具有解除紊乱、清热、安神、消激动的作用。几个世纪以来，它一直被用于治疗神经精神疾病，如癫痫、痴呆、失眠、焦虑和抑郁。本研究基于CLMD缓解大鼠癫痫症状的机制与改善自噬有关的假设。设计了几种实验方法来证明这一假设。材料与方法建立锂-匹罗卡品致痫大鼠模型。记录癫痫发作频率。透射电镜（TEM）观察海马齿状回自噬体的形态和数量。采用免疫荧光法、定量逆转录聚合酶链反应（qRT-PCR）和Western-blotting检测齿状回中Beclin-1、微管相关蛋白1A/1B轻链3 （LC3）和哺乳动物雷帕霉素靶蛋白（mTOR）的表达。结果clmd能显著降低癫痫发作频率，促进海马齿状回细胞自噬。同时，医疗干预后Beclin-1、LC3B水平明显下降，mTOR水平明显升高。结论scmd对癫痫海马齿状回自噬有促进作用，尤其是大剂量时。其机制可能与mTOR表达上调，Beclin-1和LC3B表达下调有关。
Ethnopharmacological relevanceChaihu-Longgu-Muli decoction (CLMD) is a well-known ancient formula in traditional Chinese medicine (TCM) to relieve disorder, clear away heat, tranquilize the mind and allay excitement. It has been used for the therapy of neuropsychiatric disorders such as epilepsy, dementia, insomnia, anxiety, and depression for several centuries in China.Aim of the studyThis paper is based on the assumption that the mechanism by which CLMD relieves epileptic symptoms in rats is associated with improving autophagy. Several experimental methods are designed to testify the hypothesis.Materials and methodsThe lithium-pilocarpine-induced epilepsy model was established in rats. The seizure frequency was recorded. Morphology and number of autophagosomes in hippocampal dentate gyrus was detected with a transmission electron microscope (TEM). Expression of Beclin-1, microtubule-associated proteins 1A/1B light chain 3 (LC3), and mammalian target of rapamycin (mTOR) in dentate gyrus was measured by immunofluorescence assay, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western-blotting.ResultsCLMD could significantly relieve the seizure frequency and improve autophagy in hippocampal dentate gyrus. Meanwhile, the level of Beclin-1 and LC3B decreased significantly, while mTOR increased remarkably after medical intervention.ConclusionsCLMD could improve autophagy in hippocampal dentate gyrus due to epilepsy, especially at high dose. The mechanism may be related to upregulated expression of mTOR and downregulated expression of Beclin-1 and LC3B.