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
10.3969/j.issn.1006-2157.2025.04.016
- VernacularTitle: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
- Author:
Bingxin WU
1
;
Yawen LI
2
;
Sibo HAN
1
;
Xichang HUANG
1
;
Junye MA
3
;
Xuesong Liang
4
;
Qian WU
4
;
Wenbin FU
4
Author Information
1. Second Clinical Medical College of Guangzhou University of Chinese Medicine
2. Acupuncture Rehabilitation Medical College of Guangzhou University of Chinese Medicine
3. Seventh Clinical Medical College of Guangzhou University of Chinese Medicine
4. The Second Affiliated Hospital of Guangzhou University of Chinese Medicine
- Publication Type:Journal Article
- From:
Journal of Beijing University of Traditional Chinese Medicine
2025;48(4):573-582
- CountryChina
- Language:Chinese
-
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.
- Full text:2025102910431446096Exploring the effects of _liver-smoothing and spirit-regulating_ acupuncture on intestinal flora, lipopolysaccharide, and hippocampal TLR4_NF-κB signaling pathway in depressive disorder mice.pdf
