PMID- 35294125 OWN - NLM STAT- MEDLINE DCOM- 20220503 LR - 20231003 IS - 2589-451X (Electronic) IS - 0255-2922 (Print) IS - 0255-2922 (Linking) VI - 42 IP - 1 DP - 2022 Feb TI - Effect of moxibustion on autophagy and the inflammatory response of synovial cells in rheumatoid arthritis model rat. PG - 73-82 AB - OBJECTIVE: To investigate the effect of moxibustion on synovitis and the autophagy of synoviocytes in rheumatoid arthritis (RA). METHODS: Forty Sprague-Dawley rats were randomly divided into a normal group, model group, moxibustion group, cigarette moxibustion group, and medicine group, with eight rats included in each group. The RA model was established by subcutaneous injection of complete Freund's adjuvant into the left posterior toe. Rats in the model group were not interfered with. In the moxibustion group, rats were treated by moxibustion, where a 1-cm diameter moxa stick was applied at the left Zusanli (ST 36) point. The distance of the moxa stick to the skin was 2 cm and moxibustion was completed for 20 min daily for 15 d total. In the cigarette moxibustion group, the moxa stick was replaced by a common cigarette. In the medicine group, rats were treated with a tripterygium glycoside suspension (8 mg/kg) once a day for 15 d total. In each group, the left hind limb toe volume was measured with a toe volume meter; the synovial cells were observed by hematoxylin and eosin staining; the interleukin (IL)-4, IL-6, IL-10, IL-1beta, IL-23, IL-17, and tumor necrosis factor (TNF)-alpha levels in serum were measured by enzyme-linked immunosorbent assay; the erythrocyte sedimentation rate (ESR) were detected by Westergren sedimentation rate testing; the C-reactive protein (CRP) and rheumatoid factor (RF) levels in serum were detected by rate nephelometry; the expression levels of ULK1, autophagy-associated protein (Atg)3, Atg5, and Atg12 messenger RNA (mRNA) in synovium were detected by real time-quantitative polymerase chain reaction (RT-qPCR); and the protein expression levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), mammalian target of rapamycin (mTOR), LC3-II, beclin-1, phosphorylated-PI3K (p-PI3K), p-Akt, p-mTOR in synovium were detected by Western blotting. RESULTS: Among the RA model rats, joint swelling, an inflammatory reaction, and the proliferation of synovial tissue were obvious and the signal of the PI3K/Akt/mTOR pathway was active, while autophagy was inhibited. Moxibustion at Zusanli (ST36) or intragastric administration of Tripterygium wilfordii glycosides could alleviate the inflammatory reaction of RA rats; relieve the swelling of the toes; downregulate the levels of ESR, CRF, RF; lower the levels of IL-6, IL-1beta, TNF-alpha, and IL-17; and increase the IL-4 and IL-10. At the same time, the mRNA expression levels of ULK1, Atg3, Atg5, and Atg12 and those of LC3-Ⅱ and beclin-1 were increased, while the PI3K, Akt, mTOR, p-PI3K, p-Akt, p-mTOR were decreased. Cigarette moxibustion did not significantly reduce the swelling of the toe joint in RA rats, and was not as good as that of moxibustion or Tripterygium wilfordii polyglycosides in the effects of inflammation relief and the influences of the levels of ESR, CRF, RF. While cigarette moxibustion has a weak effect to affect the expression of corresponding molecules in autophages and the expression level of the autophagy biomaker in synovial tissue. Moxibustion and tripterygium glycosides can significantly reduce the joint swelling, relieve synovitis and synovial hyperplasia, and inhibit the PI3K/Akt/mTOR signaling pathway to increase autophagy in a manner superior to cigarette moxibustion. CONCLUSION: Moxibustion can limit the proliferation of synoviocytes in RA rats by inhibiting the PI3K/Akt/mTOR signaling pathway, promoting autophagy, effectively reducing synovitis, and alleviating joint swelling. FAU - Hao, Feng AU - Hao F AD - College of Acupuncture-moxibustion and Tuina, Nanjing University of Chinese Medicine, Nanjing 210023, China. AD - Translational Medicine Research Center of Nanjing University of Chinese Medicine, Nanjing 210023, China. FAU - Wang, Qiang AU - Wang Q AD - Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu 215500, China. FAU - Liu, Lei AU - Liu L AD - College of Acupuncture-moxibustion and Tuina, Anhui University of Chinese Medicine, Hefei 230012, China. FAU - Wu, Li-Bin AU - Wu LB AD - College of Acupuncture-moxibustion and Tuina, Anhui University of Chinese Medicine, Hefei 230012, China. FAU - Cai, Rong-Lin AU - Cai RL AD - College of Acupuncture-moxibustion and Tuina, Anhui University of Chinese Medicine, Hefei 230012, China. AD - Institute of Acupuncture and Meridian, Anhui Academy of Chinese Medicine, Hefei 230038, China. FAU - Sang, Jia-Jia AU - Sang JJ AD - Affiliate Hospital of Nanjing University of Chinese Medicine/Jiangsu Province of Chinese Medicine, Nanjing 210029, China. FAU - Hu, Jun AU - Hu J AD - the first clinical medical college of Nanjing University of Chinese Medicine, Nanjing 210029, China. FAU - Wang, Jie AU - Wang J AD - College of Acupuncture-moxibustion and Tuina, Anhui University of Chinese Medicine, Hefei 230012, China. AD - Institute of Acupuncture and Meridian, Anhui Academy of Chinese Medicine, Hefei 230038, China. FAU - Yu, Qing AU - Yu Q AD - College of Acupuncture-moxibustion and Tuina, Anhui University of Chinese Medicine, Hefei 230012, China. AD - Institute of Acupuncture and Meridian, Anhui Academy of Chinese Medicine, Hefei 230038, China. FAU - He, Lu AU - He L AD - College of Acupuncture-moxibustion and Tuina, Anhui University of Chinese Medicine, Hefei 230012, China. AD - Institute of Acupuncture and Meridian, Anhui Academy of Chinese Medicine, Hefei 230038, China. FAU - Shen, Ying-Chao AU - Shen YC AD - Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu 215500, China. FAU - Miao, Yi-Ming AU - Miao YM AD - Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu 215500, China. FAU - Hu, Ling AU - Hu L AD - College of Acupuncture-moxibustion and Tuina, Anhui University of Chinese Medicine, Hefei 230012, China. AD - Institute of Acupuncture and Meridian, Anhui Academy of Chinese Medicine, Hefei 230038, China. FAU - Wu, Zi-Jian AU - Wu ZJ AD - College of Acupuncture-moxibustion and Tuina, Anhui University of Chinese Medicine, Hefei 230012, China. AD - Institute of Acupuncture and Meridian, Anhui Academy of Chinese Medicine, Hefei 230038, China. LA - eng PT - Journal Article PL - China TA - J Tradit Chin Med JT - Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan JID - 8211546 RN - 0 (Beclin-1) RN - 0 (Glycosides) RN - 0 (Interleukin-17) RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) RN - 130068-27-8 (Interleukin-10) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - *Arthritis, Rheumatoid/genetics/therapy MH - Autophagy MH - Beclin-1/metabolism MH - Glycosides MH - Humans MH - Interleukin-10 MH - Interleukin-17/genetics MH - Interleukin-6 MH - Mammals/genetics/metabolism MH - *Moxibustion MH - Phosphatidylinositol 3-Kinases MH - Proto-Oncogene Proteins c-akt MH - RNA, Messenger MH - Rats MH - Rats, Sprague-Dawley MH - *Synoviocytes MH - *Synovitis MH - TOR Serine-Threonine Kinases PMC - PMC10164637 OTO - NOTNLM OT - Arthritis, rheumatoid OT - Moxibustion OT - Synovitis; autophagy EDAT- 2022/03/17 06:00 MHDA- 2022/05/04 06:00 PMCR- 2022/01/01 CRDT- 2022/03/16 12:14 PHST- 2022/03/16 12:14 [entrez] PHST- 2022/03/17 06:00 [pubmed] PHST- 2022/05/04 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.19852/j.cnki.jtcm.20210324.002 [pii] AID - 0255-2922-42-1-73 [pii] AID - 10.19852/j.cnki.jtcm.20210324.002 [doi] PST - ppublish SO - J Tradit Chin Med. 2022 Feb;42(1):73-82. doi: 10.19852/j.cnki.jtcm.20210324.002.