北京中医药大学学报2025，Vol.48Issue(4)：573-582,10.DOI:10.3969/j.issn.1006-2157.2025.04.016
基于肠-脑轴探讨"疏肝调神"针刺对抑郁障碍小鼠肠道菌群、脂多糖和海马TLR4/NF-κB信号通路的影响
Exploring the effects of"liver-smoothing and spirit-regulating"acupuncture on intestinal flora,lipopolysaccharide,and hippocampal TLR4/NF-κB signaling pathway in depressive disorder mice based on the gut-brain axis
摘要
Abstract
Objective To investigate the effects of"liver-smoothing and spirit-regulating"acupuncture on the intestinal flora,lipopolysaccharide(LPS)and the hippocampal toll-like receptor 4(TLR4)/transcription factor(NF)-κB signaling pathway in depressive disorder mouse model,and to explore its underlying mechanisms.Methods Eighteen male SPF-grade C57BL/6J mice were randomly assigned to the control,model,and acupuncture groups using a random number method,with six mice in each group.The depression disorder model was induced in mice from both the acupuncture and model groups using CUMS.The mice in the acupuncture group were treated with acupuncture at the acupoints of"Baihui"(DU20),"Yintang"(DU29),"Hegu"(LI4),and"Taichong"(LR3)on the 15th day of modeling,with a duration of 20 min per session,once per day,for 2 consecutive weeks.Behavioral differences were assessed using the sucrose preference test,open field test,and forced swim test.Hematoxylin-eosin staining was used to observe pathological changes in the hippocampus and colon.The levels of the inflammatory factors interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α,and LPS in the hippocampus and colon were measured using Enzyme-linked Immunosorbent Assay.Western blotting was used to detect the expression of TLR4 and NF-κB protein in the hippocampus.Changes in gut microbiota structure and abundance were analyzed by 16 S rDNA sequencing.Results Compared to the control group,the model group showed reduced sucrose preference rate,time in the center area,and total distance,with an increase in immobility time(P<0.01).Inflammatory pathological changes were observed in the hippocampal CA1 region and colon.The contents of IL-1β,IL-6,TNF-α,and LPS in the hippocampus and colon increased(P<0.01).The protein expression levels of hippocampal TLR4 and NF-κB were increased(P<0.01).The Chao1 index was increased(P<0.01).The relative abundances of Pseudomonadales,Acinetobacter,Moraxellaceae,Solibacillus,Escherichia_shigella,Enterobacteriaceae,Enterobacterales,Dubosiella,and Erysipelottichales were decreased,while the relative abundances of Alloprevotella and gram_negative_bacteriurh_cTPY_13 were increased(P<0.05).The pathways of lipopolysaccharide biosynthesis and pathogenic Escherichia coli infection were upregulated,and the pathway of terpenoid backbone biosynthesis was downregulated(P<0.01).Compared to the model group,the acupuncture group showed increased sucrose preference,time in the center area,and total distance,with a decrease in immobility time(P<0.01).The inflammatory pathological changes in the hippocampal CA1 region and colon were alleviated.The contents of IL-1β,IL-6,TNF-α,and LPS in the hippocampus and colon were reduced(P<0.01).The protein expression levels of hippocampal TLR4 and NF-κB were reduced(P<0.01).The Chao1 index was decreased(P<0.05),and the relative abundances of Dubosiella and Erysipelotrichaceae were increased,while the relative abundance of Rikenellaceae,Alloprevotella,and gram_negative_bacteriuch_cTPY_13 were decreased(P<0.05).The pathways of lipopolysaccharide biosynthesis and pathogenic Escherichia coli infection were significantly downregulated,and the pathway of terpenoid backbone biosynthesis was upregulated(P<0.01).Conclusion"Liver-smoothing and spirit-regulating"acupuncture can improve depressive symptoms in depressive disorder mice,potentially through regulating the LPS and TLR4/NF-κB signaling pathway mediated by intestinal flora,reducing the inflammatory response of the hippocampus,and improving the pathological injury of the hippocampus.关键词
肠-脑轴/针刺/肠道菌群/Toll样受体4/核转录因子-κB信号通路/炎症反应/小鼠Key words
gut-brain axis/acupuncture/intestinal flora/toll-like receptor 4/nuclear factor-κB signaling pathway/inflammatory response/mice分类
医药卫生引用本文复制引用
吴炳鑫,李雅雯,韩思博,黄熙畅,马俊业,梁雪松,吴倩,符文彬..基于肠-脑轴探讨"疏肝调神"针刺对抑郁障碍小鼠肠道菌群、脂多糖和海马TLR4/NF-κB信号通路的影响[J].北京中医药大学学报,2025,48(4):573-582,10.基金项目
国家自然科学基金项目(No.U23A20507,81804199) （No.U23A20507,81804199）
广东省基础与应用基础研究基金项目(No.2024A1515010291) （No.2024A1515010291）
广东省中医药高质量发展传承创新提升工程(粤财社[2022]102号) National Natural Science Foundation of China(Nos.U23A20507 and 81804199) （粤财社[2022]102号）
