基于小鼠模型探索肠道菌群在癫痫发病机制中的作用-现代医学

基于小鼠模型探索肠道菌群在癫痫发病机制中的作用

单位：四川大学华西医院神经内科, 四川成都 610041

分类号：R742.1

出版年·卷·期（页码）：2025·53·第四期（629-638）

摘要：

目的： 基于急、慢性癫痫小鼠模型，探索肠道菌群的特征及其在癫痫发病机制中的作用。方法： 将小鼠随机分为慢性癫痫模型组、急性癫痫模型组及正常对照组3组。采用戊四氮构建慢性癫痫小鼠模型，氯化锂-匹罗卡品构建急性癫痫小鼠模型，生理盐水构建正常对照。收集所有小鼠的粪便样本，提取其中的全部肠道菌群DNA后进行16S rDNA测序，并通过生物信息学分析对代谢功能进行预测。结果： 在慢性癫痫模型组中，拟杆菌目丰度呈现先上升后下降的趋势；而急性癫痫模型组中，拟杆菌目丰度在1~3 d急剧下降，然后逐渐增高，最终恢复正常。慢性癫痫模型小鼠厚壁菌门、蓝藻菌门以及髌骨细菌门等丰度增高,而拟杆菌门丰度降低。慢性癫痫模型小鼠富集的代谢通路主要与膜转运、信号转导、环境适应和内分泌系统相关；而急性癫痫小鼠中富集的通路主要与碳水化合物的代谢、能量代谢、氨基酸代谢相关。结论： 急性癫痫发作后，肠道菌群会发生显著改变，但能够逐渐自我调节；而慢性癫痫模型小鼠肠道菌群失调持续存在。急性与慢性癫痫模型肠道菌群和代谢通路存在显著差异，提示肠道菌群失调的持续存在可能导致膜转运体系的改变，或许参与了慢性癫痫的形成。这些研究结果为深入探讨肠道菌群与癫痫形成机制提供基础，并为癫痫菌群治疗提供依据。

Objective: To characterize the epilepsy-associated fecal microbiome in mouse models of acute provoked seizures and chronic epilepsy, and explore its role in epileptogenesis. Methods: Mice were divided into three groups: a chronic epilepsy group, an acute seizure group, and a normal group. Chronic epilepsy models were induced using pentylenetetrazol, acute seizure models were induced using lithium-pilocarpine, and the normal group mice were treated with saline. Fecal samples were collected and analyzed using 16S rDNA sequencing and bioinformatics analysis. Results: In the chronic epilepsy group, the abundance of Bacteroidales initially increased and subsequently decreased. In contrast, in the acute seizure group, the abundance of Bacteroidales showed a sharp decline within 1-3 d, followed by a gradual increase, ultimately returning to normal level. In phylum level, the abundance of Firmicutes, Cyanobacteria and Patescibacteria were relatively higher, and Bacteroidetes was relatively lower in the chronic epilepsy mice model. The chronic epilepsy mice model showed enriched pathways related to membrane transport, signal transduction, environmental adaptation, the endocrine system, etc. The acute seizure mice model showed enriched pathways related to carbohydrate metabolism, energy metabolism, amino acid metabolism, etc. Conclusion: Persistent imbalance of gut microbiota may disrupt membrane transport systems, potentially contributing to the development of chronic epilepsy. These findings highlight the potential of targeting gut microbiota as a therapeutic strategy for epilepsy.

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