药学研究2026，Vol.45Issue(5)：502-509,8.DOI:10.13506/j.cnki.jpr.2026.05.004
GLP-1受体激动剂司美格鲁肽联合左乙拉西坦改善癫痫乳鼠神经炎症的机制
Mechanism study of Semaglutide combined with Levetiracetam in improving neuroinflammation in epileptic lactating mice
摘要
Abstract
Objective Neuroinflammation is a key pathological mechanism underlying refractory epilepsy in children,making targeting inflammatory pathways a potential therapeutic strategy.This study investigates the regulatory mechanism of neuroinflammation by the GLP-1 receptor agonist Semaglutide(SEM)in combination with the antiepileptic drug Levetiracetam(LEV).Methods Network pharmacology was employed to identify potential target genes for SEM-LEV therapy in pediatric epilepsy,with animal experiments validating these findings.Results Integrating network pharmacology and animal studies identified 29 common target genes between pediatric epilepsy and SEM,with neuropeptide Y receptor 1(NTR1)identified as a key hub gene.In a lithium chloride-pirocarperide-induced epileptic suckling mouse model,both SEM and LEV monotherapy significantly downregulated hippocampal NTSR1 expression,while combination therapy exhibited synergistic effects.The SEM-LEV combination improved behavioral outcomes in the epileptic suckling mouse model.SEM significantly reduced inflammatory mediators including TNF-α,IL-1β,and IL-6,with enrichment analysis confirming its enhancement of neuroinflammation mitigation via the TNF signaling pathway.Conclusion SEM modulates neuroinflammatory pathways by suppressing NTSR1 expression,thereby amplifying LEV's antiepileptic neuroprotective effects and providing novel mechanistic evidence for clinical combination therapy.关键词
司美格鲁肽/左乙拉西坦/小儿癫痫/癫痫乳鼠/神经降压素受体1/神经炎症/网络药理学Key words
Semaglutide/Levetiracetam/Pediatric epilepsy/Epileptic lactating mice/NTSR1/Neuroinflammation/Network pharmacology分类
医药卫生引用本文复制引用
刘亚丽,杜佳怡,宋雯,孙浩,张晓敏..GLP-1受体激动剂司美格鲁肽联合左乙拉西坦改善癫痫乳鼠神经炎症的机制[J].药学研究,2026,45(5):502-509,8.基金项目
山西省高等学校科技创新计划项目(No.2022L156) （No.2022L156）
山西省科学技术厅基础研究计划(自由探索类)青年项目(No.202503021212352) （自由探索类）
