中国药理学通报2025,Vol.41Issue(1) :171-178.DOI:10.12360/CPB202406075

基于"微生物-肠-脑轴"探讨补肾通腑方对APP/PS1小鼠肠道菌群及LPS/TLR4/NF-κB通路的影响

Effects of Bushen Tongfu Prescription on gut microbiota and LPS/TLR4/NF-κB pathway in APP/PS1 mice based on"microorganism-intestine-brain axis"

王旭 张杰 赵敏 宋晓雨 段建平
中国药理学通报2025,Vol.41Issue(1) :171-178.DOI:10.12360/CPB202406075

基于"微生物-肠-脑轴"探讨补肾通腑方对APP/PS1小鼠肠道菌群及LPS/TLR4/NF-κB通路的影响

Effects of Bushen Tongfu Prescription on gut microbiota and LPS/TLR4/NF-κB pathway in APP/PS1 mice based on"microorganism-intestine-brain axis"

王旭 1张杰 2赵敏 2宋晓雨 1段建平1
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作者信息

  • 1. 河南中医药大学第一附属医院脑病科,河南郑州 450000;河南中医药大学第一临床医学院,河南郑州 450000;中西医防治重大疾病河南省协同创新中心,河南郑州 450046
  • 2. 河南中医药大学第一附属医院脑病科,河南郑州 450000;中西医防治重大疾病河南省协同创新中心,河南郑州 450046
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摘要

目的 探讨补肾通腑方调控肠道菌群,改善阿尔茨海默病(Alzheimer's disease,AD)模型小鼠学习记忆能力的作用机制.方法 以APP/PS1小鼠为研究对象,给予补肾通腑方治疗8周,采用Morris水迷宫法观察小鼠空间学习记忆能力变化;16S rDNA检测小鼠肠道菌群丰度、多样性变化;HE染色观察海马病理形态学变化;免疫荧光检测海马区小胶质细胞活化情况;Western blot检测TLR4、NF-κB、IL-6等炎症因子表达.结果 与模型组相比,补肾通腑方可以缩短AD模型小鼠逃避潜伏期、游泳路径,增加跨越平台次数(P<0.05),提升肠道菌群多样性,调节肠道菌群丰度,促进海马神经元细胞损伤修复,降低iNOS/Iba1共表达,提高Arg1/Iba1共表达(P<0.01),促进小胶质细胞从M1型向M2型转化,下调TLR4、NF-κB、IL-6等促炎因子的表达.结论 补肾通腑方改善AD模型小鼠学习记忆能力的作用机制可能与调节肠道菌群介导的LPS/TLR4/NF-κB通路,从而抑制促炎型小胶质细胞活化、减轻中枢神经系统炎症、改善海马区神经元细胞损伤有关.

Abstract

Aim To explore the mechanism of Bushen Tongfu prescription(BSTF)regulating gut microbiota and improving learning and memory ability of Alzhei-mer's disease(AD)model mice.Methods APP/PS1 mice were administered by BSTF for eight weeks.The spatial learning and memory ability of mice were detected by Morris water maze.The changes in the gut microbiota abundance and diversity of mice were detec-ted by 16S rDNA technology.The morphological chan-ges of hippocampus were observed by HE staining.The expression of the activation of microglia in hippocampus was detected by immunofluorescence.The expressions of pro-inflammatory factors of TLR4,NF-κB and IL-6 in brain tissue were detected by Western blot.Results Compared with the model group,the escape latency and swimming path were shortened,the times of target crossings after removing the platform increased in BSTF groups(P<0.05),the α-diversity increased and the abundance of gut microbiota was regulated,the mor-phological structure and pathological damage of hipp-ocampal cells were improved,the co-expression of iN-OS/Iba1 decreased and the co-expression of Arg1/Iba1 increased significantly(P<0.01),the transformation of M1 to M2 of microglial cells was promoted,and the expression of TLR4,NF-κB and IL-6 protein decreased significantly.Conclusions BSTF can improve the learning and memory ability of APP/PS1 mice,and its mechanism may be related to regulating the gut micro-biota and the LPS/TLR4/NF-κB pathway,inhibiting the activation of pro-inflammatory microglia,reducing inflammation in hippocampus and improving the patho-logical damage of hippocampal cells.

关键词

阿尔茨海默病/补肾通腑方/肠道菌群/LPS/TLR4/NF-κB通路/16S/rDNA/微生物-肠-脑轴

Key words

Alzheimer's disease/Bushen Tongfu pre-scription/gut microbiota/LPS/TLR4/NF-κB path-way/16S rDNA/microbiota-gut-brain axis

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出版年

2025
中国药理学通报
中国药理学会

中国药理学通报

北大核心
影响因子:1.54
ISSN:1001-1978
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