中山大学学报（医学科学版）2025，Vol.46Issue(2)：293-300,8.
基于广州管圆线虫感染导致Balb/c小鼠大脑脱髓鞘的非靶向代谢组学分析
Untargeted Metabolomics Analysis of Demyelination in the Brain of Balb/c Mice Infected by Angiostrongylus cantonensis
摘要
Abstract
[Objective]To investigate the demyelination induced by Angiostrongylus cantonensis(AC)infection in the brain of Balb/c mice and analyze the untargeted metabolomic changes in the corpus callosum,aiming to elucidate the underlying mechanisms.[Methods]Balb/c mice were randomly assigned to a control group(n=6)and an infection group(n=6).The infection group was orally administered 30 third-stage larvae of AC,while the control group received an equal volume of saline.Body weight,visual function,and behavioral scores were measured on post-infection 3,6,9,12,15,18,and 21 days to assess neurological alterations.After 21 days,brain tissues were harvested for immunofluorescence staining,hematoxylin-eosin(HE)staining,and transmission electron microscopy to examine morphological changes in brain myelin and retina.Metabolomics analysis was performed,and differential metabolites were identified using volcano plots and heatmaps.The distribution of fold changes and bar charts were used to profile the key metabolites.These differential metabolites were then subjected to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis and regulatory network analysis.[Results]On the 9th day after AC infection,Balb/c mice showed a decline in neurological behavioral scores(P<0.05).By day 15,visual scores decreased(P<0.05),and by day 21,significant weight loss(P＜0.001)and mortality were observed.Concurrently,transmission electron microscopy and immunofluorescence staining revealed significant myelin damage in the corpus callosum and a marked reduction in oligodendrocytes(P<0.001).HE staining showed severe retinal ganglion cell damage.Metabolomic analysis revealed that glycerophospholipids were the most abundant differential metabolites,with steroids and sphingolipids being relatively less abundant.Cholesteryl ester CE(20:2)was significantly upregulated(P<0.001),while phosphatidylmethanol(18:0_18:1)was significantly downregulated(P<0.01).KEGG enrichment and regulatory network analyses demonstrated that the differential metabolites were mainly enriched in metabolic pathways like steroid biosynthesis,bile secretion,and cholesterol metabolism,and were involved in key metabolic pathways such as sphingolipid metabolism,neural signal regulation,and glycerophospholipid metabolism.[Conclusions]AC infection affects the metabolic state of mice via multiple pathways,modifying the levels of metabolites crucial for myelination and myelin stability.Demyelination may be closely linked to the disruption of these key metabolic pathways,particularly the dysregulation of cholesterol and sphingolipid metabolism,potentially playing a central role in demyelination onset.Furthermore,alterations in phospholipid metabolism and abnormal nerve signaling regulation may exacerbate myelin damage.关键词
广州管圆线虫/代谢组学/脱髓鞘/胆固醇/磷脂Key words
Angiostrongylus cantonensis/metabolomics/demyelination/cholesterol/phospholipids分类
基础医学引用本文复制引用
牛珍,吴小杰,杨亮,马芷璇,杨君雄,冯英..基于广州管圆线虫感染导致Balb/c小鼠大脑脱髓鞘的非靶向代谢组学分析[J].中山大学学报（医学科学版）,2025,46(2):293-300,8.基金项目
广州市科技计划项目(202102080053) （202102080053）
