中国病理生理杂志2025，Vol.41Issue(7)：1275-1288,14.DOI:10.3969/j.issn.1000-4718.2025.07.004
黄精多糖减轻高糖饮食诱导小鼠神经炎症的作用机制
Effects of Polygonatum sibiricum polysaccharides on high-sugar diet-in-duced neuroinflammation in mice
摘要
Abstract
AIM:To elucidate the mechanism by which Polygonatum sibiricum polysaccharides(PSP)miti-gate high-sugar diet-induced neuroinflammation through the gut microbiota-serum metabolome axis.METHODS:Fifty male ICR mice were divided into 5 groups:control group,model group,low-dose(250 mg/kg)PSP group,high-dose(500 mg/kg)PSP group,and donepezil hydrochloride(3 mg/kg)group.The neuroinflammation model was established through administration of high-sugar chow and 10%sucrose water for 12 weeks.Cognitive function assessment was per-formed utilizing the Morris water maze.Hippocampal histopathology was examined by hematoxylin-eosin(HE)staining,activated microglia were assessed via immunofluorescence,and neuronal apoptosis was evaluated by TUNEL assay.Serum and hippocampal levels of interleukin-6(IL-6),IL-1β,tumor necrosis factor-α(TNF-α)and nitric oxide(NO)were quantified using ELISA and Western blot.Gut microbiota diversity and serum untargeted metabolomics analyses were car-ried out employing 16S rRNA sequencing and LC-MS/GC-MS,respectively.Differential metabolites were screened,and key metabolic pathways were enriched using MetaboAnalyst 6.0.Spearman correlation analysis established relationships between gut microbiota,metabolites,and inflammatory factors.RESULTS:Model mice demonstrated increased escape latency(P<0.05 or P<0.01)and decreased platform crossings(P<0.01)compared with controls,which were reversed by PSP treatment(P<0.05 or P<0.01).Treatment with PSP substantially reduced IL-6,IL-1β,TNF-α and NO levels in se-rum and hippocampus(P<0.05 or P<0.01),diminished inflammatory infiltration,inhibited microglial activation,and re-duced neuronal damage.Gut microbiota analysis demonstrated that PSP increased Lactobacillus and Bacteroides abun-dance while reducing Alistipes(P<0.05).Metabolomics identified 15 differential metabolites(including betaine,kyotor-phin and ε-caprolactam)and highlighted the significance of alanine,aspartate and glutamate metabolism pathways.Spear-man analysis revealed that abundance of Alistipes and Bacteroides were positively correlated with IL-1β(P<0.05),while abundance of Lactobacillus was negatively correlated with inflammatory factors(P<0.05 or P<0.01).Key metabolites(be-taine,kyotorphin,ε-caprolactam,trans-cinnamate,cis-zeatin and galactitol)showed strong associations with inflamma-tion factors(P<0.05 or P<0.01).CONCLUSION:Treatment with PSP attenuates neuroinflammation through modula-tion of gut microbiota(Lactobacillus,Bacteroides and Alistipes),regulation of metabolites(betaine,kyotorphin and so on),and targeting amino acid metabolism pathways.关键词
黄精多糖/高糖饮食/神经炎症/肠道菌群/血清非靶向代谢组学Key words
Polygonatum sibiricum polysaccharide/high-sugar diet/neuroinflammation/gut microbiota/un-targeted serum metabolomics分类
医药卫生引用本文复制引用
徐东方,孙嘉辰,杜睿,朱柯颖,夏颖斐,吴亮亮,王洋..黄精多糖减轻高糖饮食诱导小鼠神经炎症的作用机制[J].中国病理生理杂志,2025,41(7):1275-1288,14.基金项目
黑龙江省博士后资助项目(No.LBH-Z23294) （No.LBH-Z23294）
齐齐哈尔市科技计划联合引导项目(No.LSFGG-2023035) （No.LSFGG-2023035）
国家级大学生创新训练项目(No.202411230002) （No.202411230002）
