陆军军医大学学报2026，Vol.48Issue(7)：882-894,13.DOI:10.16016/j.2097-0927.202601037
司美格鲁肽通过调控炎症改善自闭症谱系障碍模型小鼠的核心症状
Semaglutide ameliorates core symptoms in mouse model of autism spectrum disorder by regulating inflammation-related pathways
摘要
Abstract
Objective Based on the neuroprotective and anti-inflammatory properties of semaglutide,this study aims to investigate whether semaglutide improves core symptoms in BTBR T(+)Itpr3(tf)/J(BTBR)mice,a model of autism spectrum disorder(ASD),through modulation of inflammation-related targets and signaling pathways.Methods A total of 32 male C57BL/6J(C57)and BTBR mice(7 weeks old)were randomly divided into 4 groups(n=8):The treatment group received intraperitoneal injection of 25 nmol/kg semaglutide,while the control group received normal saline,with continuous intervention for 7 d,and body weight was monitored continuously throughout the intervention period.Mouse behavioral indicators were evaluated using various behavioral tests,including the three-chamber sociability test,grooming test,marble-burying test,novel object recognition test,Y-maze test and open field test.After behavioral assessments,the brain tissues were collected,and network pharmacology,GO/KEGG enrichment analysis,protein-protein interaction analysis,molecular docking technology,and qRT-PCR were employed to explore the potential mechanisms of semaglutide.Results Semaglutide intervention for 7 d significantly reduced the body weight of BTBR mice(P<0.05),increased the preference index from chamber time(P<0.01)and preference index from sniffing time(P<0.05),elevated the novel object recognition discrimination index(P<0.01),and reduced repetitive stereotyped behaviors such as self-grooming(P<0.001)and marble burying(P<0.01).However,no significant effects on the above mentioned behaviors were observed in C57 mice,and no obvious impact on locomotor activity was demonstrated in the open field test.Network pharmacology analysis identified 78 common targets which enriched in inflammation-related pathways.Semaglutide exhibited favorable binding affinity with potential targets in inflammation-related pathways including Serpine1,Mmp9,Pparg,Stat3,Ppara,and Nr1h3,with binding energies all≤-4 kcal/mol.qRT-PCR further confirmed that semaglutide intervention significantly downregulated mRNA expression levels of Serpine1,Mmp9,Stat3,Il6,Tnfa,Il17a,and Il1b(P<0.05),and upregulated Pparg expression(P<0.05)in the hippocampus of BTBR mice.Conclusion Semaglutide alleviates ASD-like symptoms in BTBR mice by regulating inflammation-related pathways,thus offering a promising potential treatment and foundational research for the clinical management of ASD.关键词
司美格鲁肽/孤独症/BTBR小鼠/神经炎症Key words
semaglutide/autism spectrum disorder/BTBR mice/neuroinflammation分类
医药卫生引用本文复制引用
刘嘉音,刘天曜,罗静,张星高,龚美凤,郭黎,范晓棠..司美格鲁肽通过调控炎症改善自闭症谱系障碍模型小鼠的核心症状[J].陆军军医大学学报,2026,48(7):882-894,13.基金项目
国家自然科学基金面上项目(32471027) Supported by the General Program of National Natural Science Foundation of China(32471027). （32471027）
