OBJECTIVE: To explore whether moxibustion exerts therapeutic effects on rheumatoid arthritis(RA) by regulating the expression of T-cell immunoglobulin and mucin-containing protein-3(TIM-3) and subsequently modulating ...OBJECTIVE: To explore whether moxibustion exerts therapeutic effects on rheumatoid arthritis(RA) by regulating the expression of T-cell immunoglobulin and mucin-containing protein-3(TIM-3) and subsequently modulating the macrophage M1 polarization toll-like receptor 4(TLR4)-myeloid differentiation factor 88(My D88)-nuclear factor kappa B(NF-κB) signaling pathway. METHODS: We utilized moxibustion treatment in RA rat models using the Zusanli(ST36) and Shenshu(BL23) acupoints. Hematoxylin and eosin(HE) staining was used to observe the pathological changes of the synovial tissue under a section light microscope, and pathological scoring was performed according to the grading standard of the degree of synovial tissue disease. Enzyme-linked immunosorbent assay(ELISA) was applied to verify the efficacy of moxibustion in reducing inflammation. Quantitative real-time polymerase chain reaction(q RTPCR) was used to detect the expression of the TIM-3/TLR4-My D88-NF-κB signaling pathway-related molecules, and Western blot was used to detect the contents of synovial NF-κB. RESULTS: We established the Freund's complete adjuvant(FCA)-induced RA model in rats. The expression level of M1 polarization signaling pathway TLR4-My D88-NF-κB and the inflammatory factors interleukin-12(IL-12), tumor necrosis factor alpha(TNF-α), and tumor necrosis factor beta(TNF-β) were significantly increased in the RA model. After moxibustion treatment, the expression level of TLR4-My D88-NF-κB was significantly decreased, and the inflammatory factors IL-12, TNF-α, and TNF-β were decreased, but the expression level was significantly increased in the RA model. When TIM-3 expression was inhibited, the expression level of TLR4-My D88-NF-κB, and the inflammatory factors IL-12, TNF-α, and TNF-β were not suppressed, even after moxibustion treatment. CONCLUSIONS: Moxibustion regulates the key target TIM-3 by acting on the Zusanli(ST36) and Shenshu(BL23) points, thereby inhibiting the M1 polarization of macrophages;that is, it inhibits the TLR4-My D88-NF-κB signaling pathway, and finally achieves alleviation of pathological changes and anti-inflammatory effects.展开更多
基金the National Natural Science Foundation of China:Study on Immunoregulatory Mechanism of Moxibustion"Regulating Weiqi"to Regulate the Intrasynovial Environment Steady State in Rheumatoid Arthritis Model Rats based on the Skin-resident Memory T cells-Growth Arrest-specific 6/Mer Tyrosine Kinase (No. 82374587)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"(No. 81973959)+1 种基金the National Key R&D Program of China:Research on the Functional Characteristics of"Special Effects"and"Common Effects"of Acupoints (No. 2019YFC1709001)Science and Technology Innovation Seedling Project of Sichuan Province:based on Macrophage M1 Polarization Signaling Pathway Toll-like receptor 4/Myeloid differentiation factor 88/Nuclear factor kappa B and its Regulatory Molecule T-cell Immunoglobulin and Mucin-containing Protein-3 Exploring the Effect Mechanism of Moxibustion on Experimental Rheumatoid Arthritis Model (No. 2022037)。
文摘OBJECTIVE: To explore whether moxibustion exerts therapeutic effects on rheumatoid arthritis(RA) by regulating the expression of T-cell immunoglobulin and mucin-containing protein-3(TIM-3) and subsequently modulating the macrophage M1 polarization toll-like receptor 4(TLR4)-myeloid differentiation factor 88(My D88)-nuclear factor kappa B(NF-κB) signaling pathway. METHODS: We utilized moxibustion treatment in RA rat models using the Zusanli(ST36) and Shenshu(BL23) acupoints. Hematoxylin and eosin(HE) staining was used to observe the pathological changes of the synovial tissue under a section light microscope, and pathological scoring was performed according to the grading standard of the degree of synovial tissue disease. Enzyme-linked immunosorbent assay(ELISA) was applied to verify the efficacy of moxibustion in reducing inflammation. Quantitative real-time polymerase chain reaction(q RTPCR) was used to detect the expression of the TIM-3/TLR4-My D88-NF-κB signaling pathway-related molecules, and Western blot was used to detect the contents of synovial NF-κB. RESULTS: We established the Freund's complete adjuvant(FCA)-induced RA model in rats. The expression level of M1 polarization signaling pathway TLR4-My D88-NF-κB and the inflammatory factors interleukin-12(IL-12), tumor necrosis factor alpha(TNF-α), and tumor necrosis factor beta(TNF-β) were significantly increased in the RA model. After moxibustion treatment, the expression level of TLR4-My D88-NF-κB was significantly decreased, and the inflammatory factors IL-12, TNF-α, and TNF-β were decreased, but the expression level was significantly increased in the RA model. When TIM-3 expression was inhibited, the expression level of TLR4-My D88-NF-κB, and the inflammatory factors IL-12, TNF-α, and TNF-β were not suppressed, even after moxibustion treatment. CONCLUSIONS: Moxibustion regulates the key target TIM-3 by acting on the Zusanli(ST36) and Shenshu(BL23) points, thereby inhibiting the M1 polarization of macrophages;that is, it inhibits the TLR4-My D88-NF-κB signaling pathway, and finally achieves alleviation of pathological changes and anti-inflammatory effects.
