Advanced Search

Journal of Traditional Chinese Medicine >

2024 , Vol. 44 >Issue 4: 753 - 761

DOI: https://doi.org/10.19852/j.cnki.jtcm.20240610.003

Original articles

Study on the anti-inflammatory mechanism of moxibustion in rheumatoid arthritis in rats based on phospholipaseA2 signaling inhibition by Annexin 1

  • Yanding GUO ,
  • Kun LUO ,
  • Linlin ZHANG ,
  • Wenting LU ,
  • Yanan SHANG ,
  • Yumei ZHONG ,
  • Danhui HU ,
  • Xin YANG ,
  • Haiyan ZHOU
Expand
  • 1 Department of Acupuncture-Moxibustion and Tuina, the Third Affiliated Hospital, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
    2 Department of Chengdu Integrated Traditional Chinese Medicine and Western Medicine Hospital, Chengdu 610075, China
    3 External Treatment Center, First People's Hospital of Chengdu, Chengdu 610095, China
    4 Department of Health Rehabilitation School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China

Received date: 2023-02-12

  Accepted date: 2023-07-20

  Online published: 2024-06-10

Supported by

National Natural Science Foundation of China: Study on the Immune Mechanism of Macrophages 1/Macrophages 2 Polarization of Macrophages Treated with Moxibustion "Strengthening the Body and Expelling Pathogenic Qi" for "Struggle Between Healthy Qi and Pathogenic Qi" in Rheumatoid Arthritis(81973959);National Key R&D Program of China: a Comparative Study of Moxibustion at Zusanli (ST36) on the Polarization of Knee Synovial Macrophage in Kneeosteoar-thritis and Rheumatoid Arthritis Rat Models(2019YFC1709001);National Natural Science Foundation of China: Study on the Regulatory Mechanism of the "Immune-Inflammation" Molecular Signal of the Nucleotide—Binding Oligomerization Domain, Leucine rich Repeat and Pyrin domain containing Proteins 3 Inflammasome Treated by Moxibustion for Rheumatoid Arthritis(81774435);Foundation of Chengdu University of Traditional Chinese Medicine: Study on the Mechanism of " Macrophage Migration Inhibitory Factor -Target Protein-Glucocorticoid-Inflammation" in Moxibustion Treatment and Anti-inflammatory Effect of Rheumatoid Arthritis(QNXZ2018034);Science and Technology Innovation Seedling Project of Sichuan Province: Exploring the Effector Mechanism of Moxibustion Treatment in the Experimental Rheumatoid Arthritis Model based on the Macrophage Macrophages 1 Polarization Signaling Pathway Toll-like Receptors 4-Maximum Tolerated Dose 88- Nuclear Factor-Kappa B and its Regulatory Molecule T Cell Immunoglobulin and Mucin Domain-containing Protein 3(2022037)

Fold

Abstract

OBJECTIVE: To determine whether moxibustion had an anti-inflammatory effect on rheumatoid arthritis (RA) by regulating Annexin 1 expression and interfering with the phospholipaseA2 signaling pathway.

METHODS: Thirty male Sprague-Dawley rats were randomly categorized into five groups (six rats per group): blank control (CON) group, RA model (RA) group, moxibustion (MOX) group, Annexin 1 lentiviral intervention (RNAi-Anxa1) group, and Annexin 1 lentiviral intervention + moxibustion (RNAi-Anxa1 + MOX) group. The rats in the RNAi-Anxa1 and the RNAi-Anxa1 + MOX groups were injected with the lentiviral vector-mediated RNAi-Anxa1 into the rat foot pad. An experimental RA rat model was established by injecting Freund's complete adjuvant (FCA) into the RA, MOX, RNAi-Anxa1, and RNAi-Anxa1 + MOX groups. Rats in the MOX and RNAi-Anxa1 + MOX groups received moxibustion treatment. After modeling, using moxibustion “Shenshu (BL23)” and “Zusanli (ST36)”, each point is 5 times, bilateral alternating, once a day, 6 times for a course of treatment, between the courses of rest for a one day. A total of three treatment courses were conducted. Both bilateral pad thicknesses were measured using Vernier calipers on experimental days 1, 7, 14, 21, and 28. The expression of cPLA2α signaling in the synovium of diseased joints was observed using Western blot. The pathology of the rat ankle synovium was observed using hematoxylin-eosin (HE) staining. Interleukin (IL)-1β, IL-10, prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) were detected using enzyme-linked immunosorbent assay.

RESULTS: Moxibustion increased the levels of Annexin 1 and decreased the inflammatory response in rats with RA. After increasing the expression of Annexin 1, the phosphorylated expression of cPLA2α was inhibited, the serum levels of IL-1β, PGE2, and LTB4 decreased, and the level of IL-10 increased. In moxibustion treated RA rats after the Annexin 1 lentiviral intervention, the serum levels of IL-1β, PGE2, LTB4, and IL-10 were almost unchanged.

CONCLUSION: Moxibustion enhanced the negative regulation of the cPLA2α signaling pathway, increased the synovial Annexin 1 expression, inhibited the cPLA2α signaling pathway, indirectly inhibited the expression of downstream inflammatory factors, and played a role in reducing inflammation.

Key words： annexins; group IV phospholipases A2; signal transduction; moxibustion; arthritis, rheumatoid

Cite this article

Yanding GUO , Kun LUO , Linlin ZHANG , Wenting LU , Yanan SHANG , Yumei ZHONG , Danhui HU , Xin YANG , Haiyan ZHOU . Study on the anti-inflammatory mechanism of moxibustion in rheumatoid arthritis in rats based on phospholipaseA2 signaling inhibition by Annexin 1[J]. Journal of Traditional Chinese Medicine, 2024 , 44(4) : 753 -761 . DOI: 10.19852/j.cnki.jtcm.20240610.003

References

1. Jing W, Yuan Q, Yu PZ, Jia XD, Q HY. Rhamm induces progression of rheumatoid arthritis by enhancing the functions of fibroblast-like synoviocytes. BMC musculoskeletal disorders 2018; 19: 455.
2. Moudgil KD. Advances in the pathogenesis and treatment of autoimmunity. Cell Immunol 2019; 339: 1-3.
3. The Rheumatology Branch of the Chinese Medical Association. Guidelines for the diagnosis and treatment of rheumatoid arthritis. Chin J Rheumatol 2010; 14: 265-70.
4. Perretti M, D’Acquisto F. AnnexinA1 and glucocoeticoids as effectors of the resolution of inflammation. Nat Rev Immunol 2009; 9: 62-70.
5. Daniel A, Yuan Y, Ashley M, Lanie S, Michelle L, Eric FM. Endogenous macrophage migration inhibitory factor modulates glucocorticoid sensitivity in macrophages via effects on MAP kinase phosphatase-1 and p38 MAP kinase. FEBS Lett 2006; 580: 974-81.
6. Daun JM, Cannon JG. Macrophage migration inhibitory factor antagonizes hydrocortisone induced increases in cytosolic ikappa balpha. Am J Physiol Regul Integr Comp Physiol 2000; 279: R1043-9.
7. Li CZ, Li SY, Wang JJ. The anti-inflammatory effects of MIF against glucocorticoids and its mechanisms. Zhong Guo Mian Yi Xue 2013; 11:1146-50.
8. Sun Y, Han S, Wang JJ. the effect of siRNA silencing genes on glucocorticoid hormones to inhibit the release of lipid inflammatory mediators and its mechanism. Chin J Pathophysiol 2023; 10: 1803-6.
9. Qin C, Yang YH, May L. Cardio protective epoten-tial of annexin-A1 mimetic sinmyo cardial in farction. Pharmacol Ther 2015; 148: 47-65.
10. Horlacher T, Noti C, Paz DJL, et al. Characterization of annexin Al glycan binding reveals binding to highly sulfated glycans with preference for highly sulfated heparan sulfate and heparin. Biochemistry 2015; 2650-9.
11. Bizzarro V, Fontanella B, Franceschelli S, et al. Role of Annexin Al in mouse myoblast cell differentiation. J Cell Physiol 2010; 224: 757-65.
12. Mauro P, Fulvio D'A. Annexin A1 and glucocorticoids as effectors of the resolution of Inflammation. Nat Rev Immunol 2009; 9: 92-70.
13. Gao J, Liu XG, Zhou HY, Yang LC, Hou JY, Yu XX. Explore the HPAA circadian basis of moxibustion anti-inflammatory effect from the nighttime ACTH and CS levels of RA rats. Zhong Hua Zhong Yi Ji Chu Yi Xue 2010; 16: 515-16+23.
14. Gao J, Liu XG, Huang JJ, et al. HPAA in moxibustion in regulating NF-kB signaling in the synovial tissue of rats with rheumatoid arthritis. Zhen Ci Yan Jiu 2010; 35: 198-203.
15. Gao J, Zhou HY, Liu XG, Tang Y. Experimental study on the effects of moxibustion on plasma th1/th2 cytokines balance in experimental RA rats. Chengdu Zhong Yi Yao Da Xue Xue Bao 2008; 31: 21-3.
16. Ren JG, Liu XG, Lei X. Moxibustion therapy Study on the anti-inflammatory effect and its effect on MPD-1 expression in experimental rats. Shi Zhen Guo Yi Guo Yao 2017; 28: 3048-50.
17. Zhong YM, Zhang LL, Lu WT, Shang YN, Zhou HY. Moxibustion regulates the polarization of macrophages through the IL-4/STAT6 pathway in rheumatoid arthritis. Cytokine 2022; 152: 155835.
18. Zhou HY, Liu XG, Gao J. Research of moxibustion influence on GR and MEL1B expressions in hippocampus of experimental RA rats. Liaoning Zhong Yi Za Zhi 2012; 39: 2313-5.
19. Zhou HY, Liu XG, Huang DJ, et al. Study of moxibustion regulating RA rats' HPAA functional glucocorticoid receptor mechanism. Zhong Hua Zhong Yi Yao Xue Kan 2010; 28: 1167-9.
20. Shalev M. APHIS, FDA, and NIH issue memorandum of understanding on laboratory animal welfare. Lab animal 2006; 35: 13.
21. Shi XP, Zong AN, Tao J, Wang ZL. Study of instructive notions with respect to caring for laboratory animals. Zhong Guo Yi Ke Da Xue Xue Bao 2007; 36: 493.
22. Li ZR. Experimental Acupuncture Science. 2nd ed. Beijing: Zhong Guo Zhong Yi Yao Chu Ban She, 2007: 255-7.
23. Chen Q. Methodology of Chinese Medicine. 2nd ed. Beijing: People's Health Publishing House, 2006; 1-3.
24. Zhou B. Effects of lentivirus-mediated RNAi silencing of IL-1 type I receptors on the MAPKs pathway in rat knee arthritis. Shanghai: Shanghai Fudan University 2009; 1-56.
25. Li Y, Liu R, Chu YK, et al. The effect of shRNA silencing of the ANXA1 gene on FPR1 and F-actin expression. Ningxia Med J 2020; 390-3.
26. Hu JG. Chen XJ. Professor Chen Xiangjun discusses on the experience analysis of treating rheumatoid arthritis. Zhong Guo Dang Dai Yi Yao 2020; 12: 157-9, 63.
27. Choi TY, Kim TH, Kang JW, Lee MS, Ernst E. Moxibustion for rheumatic conditions: a systematic review and Meta-analysis. Clin Rheumatol 2011; 30: 937-45.
28. Shang YN. Study on the mechanism of IKKβ/I κ B- α in exploring the anti-inflammatory effect of moxibustion in rheumatoid arthritis rats based on the NF- κB signaling pathway. Chengdu: Chengdu University of Traditional Chinese Medicine, 2021: 1-67.
29. Zhang LL, Zhong YM, Lu WT, et al. Moxibustion of Zusanli (ST36) and Shenshu (BL23) alleviates the inflammation of rheumatoid arthritis in rats through regulating macrophage migration inhibitory factor/ glucocorticoids signaling. J Tradit Chin Med 2024; 44: 353-61.
30. Lee MS, Shin BC, Ernst E. Acupuncture for rheumatoid arthritis: a systematic review. Rheumatology 2008; 47: 1747-53.
31. Ibfelt EH, Jacobsen RK, Kopp TI, Cordtz RL, Jakobsen AS, Seersholm N. Methotrexate and risk of interstitial lung diseaseand respiratory failure in rheumatoid arthritis: an ationwide population-based study. Rheumatology (Oxford) 2021; 60: 346-52.
32. Tu J, Hong W, Zhang P, Wang X, K?rner H, Wei W. Ontology and function of fibroblast-like and macrophage-like synoviocytes: how do they talk to each other and can they be targeted for rheumatoid arthritis therapy? Front Immunol 2018; 9: 1467.
33. Ma WK, Yao H, Huang Y. The combination of activator protein-1 nuclear factor-kB regulates synovial cell proliferation and apoptosis mechanisms in rheumatoid arthritis. Chin J Rheumatol 2014; 18: 345-7.
34. Elshabrawy HA, Chen Z, Volin MV, Ravella S, Virupannavar S, Shahrara S. The path-ogenie role of an giogenesis in rheumatoid arthrit. Angio-genesis 2015; 18: 433-48.
35. Solito E, Coupa de CD, Parente L, Flower RJ, Russo-Marie F. IL-6 stimulates Annexin 1 expression and translocation and suggests a new biological role as class Ⅱ acutephase protein. Cytokine 1998; 10: 514-21.
36. Mizuno H, Uemura K, Moriyama A, et al. Glucocorticoid induced the expression of mRNA and the secretion of lipocortin1 in rat astrocytoma cells. Brain 1997; 746: 256-64.
37. Antonicelli F, De Coupade C, Russo-Marie F, Le Garrec Y. CREB is involved in mouse annexin A1 regulation by cAMP and glucocorticoids. Eur J Biochem 2001; 268: 62-9.
38. Kim SW, Rhee HJ, Ko J, et al. Inhibition of cytosolic phospholipase A2 by annexin I. Specific interaction model and mapping of the interaction site. J Biol Chem 2001; 276: 15712-9.
39. Ford-Hutchinson AW. Leukotriene B4 in inflammation. . Crit Rev Immunol 1990; 10: 1-12.
40. Woodward DF, Jones RL, Narumiya S. International union of basic and clinical pharmacology. LXXXⅢ: classification of prostanoid receptors, updating 15 years of progress. Pharmacol Rev 2011; 63: 471-538.
41. Dong ZF. Progress in bone destruction of rheumatoid arthritis. Shi Jie Zui Xin Yi Xue Xin Xi Wen Zhai 2018; 18: 43-4.
42. Wu LM, Ye JF, Xie WH. Role of leukotriene B4 in the pathogenesis of rheumatoid arthritis. Zhong Guo Mian Yi Xue Za Zhi 2014; 30: 689-93.
Options
Outlines

/

〈 〉