Moxibustion of Zusanli (ST36) and Shenshu (BL23) alleviates the inflammation of rheumatoid arthritis in rats through regulating macrophage migration inhibitory factor/glucocorticoids signaling

  • Linlin ZHANG ,
  • Yumei ZHONG ,
  • Wenting LU ,
  • Yanan SHANG ,
  • Yanding GUO ,
  • Xiaochao LUO ,
  • Yang CHEN ,
  • Kun LUO ,
  • Danhui HU ,
  • Huiling YU ,
  • Haiyan ZHOU
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  • 1 Acupuncture and Moxibustion College, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
    2 Department of Painology, First People's Hospital of Chengdu, Chengdu 610095, China
    3 Chinese Evidence-Based Medicine Centre, West China Hospital, Sichuan University, Chengdu 610044, China
    4 Traditional Chinese Medicine College, Chongqing Medical University, Chongqing 400016, China
    5 External treatment center, First People's Hospital of Chengdu, Chengdu 610095, China

Received date: 2022-03-12

  Accepted date: 2022-05-22

  Online published: 2022-06-02

Supported by

National Key R&D Program of China: Research on the Functional Characteristics of "Special Effects" and "Common Effects" of Acupoints(2019YFC1709001);The National Natural Science Foundation of China: Study on the Immune Mechanisms of Macrophage M1/M2 Polarization in the Treatment of Rheumatoid Arthritis by Moxibustion "Strengthening Body Resistance and Eliminating Evil"(81973959);Research on "Immune-Inflammation" Molecular Signal Regulation of NLRP3 Inflammasomes in RA with Moxibustion Treatment(81774435);Foundation of Sichuan Provincial Administration of Traditional Chinese Medicine: Research on the Mechanism of MIF-GC Rhythm in the Anti-inflammatory Effect of Moxibustion in Treating Rheumatoid Arthritis(2018JC007);Science and Technology Innovation Seedling Project of Sichuan Province, China: based on Macrophage M1 Polarization Signaling Pathway TLR4-MyD88-NF-κB and Its Regulatory Molecule TIM-3 Exploring the Effect Mechanism of Moxibustion on Experimental RA Model(2022037);Chengdu University of Traditional Chinese Medicine Foundation: Study on the Mechanism of "MIF-target Protein-GC-inflammation" in the Anti-Inflammatory Effect of Moxibustion in the Treatment of RA(QNXZ2018034)

Abstract

OBJECTIVE: To test the hypothesis that moxibustion may inhibit rheumatoid arthritis (RA) synovial inflammation by regulating the expression of macrophage migration inhibitory factor (MIF)/glucocorticoids (GCs).

METHODS: Fifty male Sprague-Dawley rats were randomly divided into five groups (n = 10 each): blank Control (CON) group, RA Model (RA) group, Moxibustion (MOX) group, MIF inhibitor (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) group, and Moxibustion + MIF inhibitor ISO-1 (MOX + ISO-1) group. Rats in the ISO-1 group and ISO-1 + MOX group were intraperitoneally injected with the inhibitor ISO-1. The rats in the RA group, ISO-1 group, MOX group, and ISO-1 + MOX group were injected with Freund's complete adjuvant (FCA) in the right hind footpad to establish an experimental RA rat model. In the MOX group and MOX + ISO-1 group, rats were treated with Moxa. The thickness of the footpads of the rats in each group was measured at three-time points before, after modeling and after moxibustion treatment. The contents of serum MIF, corticosterone (CORT), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay; and the contents of synovial MIF were detected by Western blot. Hematoxylin-eosin (HE) staining method was used to observe the pathological changes of synovial tissue under a section light microscope, and pathological scoring was performed according to the grading standard of the degree of synovial tissue disease.

RESULTS: Moxibustion was found to reduce the level of MIF and alleviate inflammation in RA rats in this study. In addition, after inhibiting the expression of MIF, the level of CORT increased, and the level of TNF-α decreased. Treating RA rats with inhibited MIF by moxibustion, the level of CORT was almost unchanged, but the level of TNF-α further decreased. The correlation analysis data suggested that MIF was positively related to the expression of TNF-α and negatively correlated with the expression of CORT.

CONCLUSION: Reducing MIF to increase CORT and decrease TNF-α by moxibustion treatment in RA. MIF may be a factor for moxibustion to regulate the expression of CORT, but the expression of TNF-α is due to the incomplete regulation of the MIF. This study added to the body of evidence pointing to moxibustion's anti-inflammatory mechanism in the treatment of RA.

Cite this article

Linlin ZHANG , Yumei ZHONG , Wenting LU , Yanan SHANG , Yanding GUO , Xiaochao LUO , Yang CHEN , Kun LUO , Danhui HU , Huiling YU , Haiyan ZHOU . Moxibustion of Zusanli (ST36) and Shenshu (BL23) alleviates the inflammation of rheumatoid arthritis in rats through regulating macrophage migration inhibitory factor/glucocorticoids signaling[J]. Journal of Traditional Chinese Medicine, 2024 , 44(2) : 353 -361 . DOI: 10.19852/j.cnki.jtcm.20220602.001

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