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1.绵阳市中医医院(四川 绵阳 621000)
2.贵州中医药大学(贵州 贵阳 550002)
康勤龙,男,硕士,主治医师,主要从事中西医结合防治风湿免疫疾病的临床研究工作
李开楊,主治医师;E-mail: 1592877812@qq.com
收稿日期:2024-07-09,
纸质出版日期:2025-07-10
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康勤龙,李开楊,高闻,等.mTOR信号通路在防治类风湿关节炎中的作用及中医外治法干预的研究进展[J].上海中医药杂志,2025,59(7):88-92.
KANG Qinlong,LI Kaiyang,GAO Wen,et al.mTOR signaling pathway in prevention and treatment of rheumatoid arthritis and research progress on traditional Chinese medicine external treatments[J].Shanghai Journal of Traditional Chinese Medicine,2025,59(7):88-92.
康勤龙,李开楊,高闻,等.mTOR信号通路在防治类风湿关节炎中的作用及中医外治法干预的研究进展[J].上海中医药杂志,2025,59(7):88-92. DOI: 10.16305/j.1007-1334.2025.z20240709004.
KANG Qinlong,LI Kaiyang,GAO Wen,et al.mTOR signaling pathway in prevention and treatment of rheumatoid arthritis and research progress on traditional Chinese medicine external treatments[J].Shanghai Journal of Traditional Chinese Medicine,2025,59(7):88-92. DOI: 10.16305/j.1007-1334.2025.z20240709004.
类风湿关节炎(RA)是一种慢性自身免疫性疾病,主要累及关节和关节周围软组织。本病发病机制尚不明确,目前认为其与细胞炎症、自噬等密切相关。哺乳动物雷帕霉素靶蛋白(mTOR)是一种调节细胞生长、存活、代谢和免疫的蛋白激酶,其被激活后可通过调控炎症反应、细胞自噬等多种途径,参与RA的发生发展。近年来,中医外治法在治疗RA领域取得长足进步,且具有独特优势,其可通过调控mTOR相关信号通路,增强自噬活性,抑制细胞增殖,促进细胞凋亡,减轻炎症反应,从而改善RA。基于此,通过检索mTOR信号通路在RA中的作用以及中医外治法靶向这一信号通路治疗RA的相关文献并进行综述,以期为RA的机制研究和临床治疗提供参考。
Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints and periarticular soft tissues. Although its exact pathogenesis remains unclear, it is believed to be closely associated with cellular inflammation and autophagy. Mammalian target of rapamycin (mTOR) is a protein kinase that regulates cell growth, survival, metabolism, and immunity. Upon activation, mTOR influences the development and progression of RA by modulating inflammatory response and autophagy. In recent years, traditional Chinese medicine (TCM) external treatments have made significant progress in the treatment of RA and have unique advantages. These treatments can improve RA by modulating mTOR-related signaling pathways, enhancing autophagic activity, inhibiting cell proliferation, promoting apoptosis, and reducing inflammation. Therefore, we reviewed relevant literature on the role of the mTOR signaling pathway in RA and TCM external treatments targeting this signaling pathway in the treatment of RA, with the aim of providing insights for RA mechanism research and clinical treatment.
PASCUAL-GARCÍA S , MARTÍNEZ-PEINADO P , PUJALTE-SATORRE C , et al . Exosomal osteoclast-derived miRNA in rheumatoid arthritis: From their pathogenesis in bone erosion to new therapeutic approaches [J]. Int J Mol Sci , 2024 , 25 ( 3 ): 1506 .
ALMUTAIRI K , NOSSENT J , PREEN D , et al . The global prevalence of rheumatoid arthritis: a meta-analysis based on a systematic review [J]. Rheumatol Int , 2021 , 41 ( 5 ): 863 - 877 .
MARQUES-RAMOS A , CERVANTES R . Expression of mTOR in normal and pathological conditions [J]. Mol Cancer , 2023 , 22 ( 1 ): 112 .
WANG X H , SHEN C P , WANG T T , et al . Shikonin suppresses rheumatoid arthritis by inducing apoptosis and autophagy via modulation of the AMPK/mTOR/ULK-1 signaling pathway [J]. Phytomedicine , 2024 , 128 : 155512 .
REN M , MA K , PANG X , et al . Anti-rheumatoid arthritis effects of total saponins from Rhizoma Panacis Majoris on adjuvant-induced arthritis in rats and rheumatoid arthritis fibroblast-like synoviocytes [J]. Phytomedicine , 2023 , 119 : 155021 .
MANE R R , KALE P P . The roles of HDAC with IMPDH and mTOR with JAK as future targets in the treatment of rheumatoid arthritis with combination therapy [J]. J Complement Integr Med , 2022 , 20 ( 4 ): 689 - 706 .
XIE Y , LEI X , ZHAO G , et al . mTOR in programmed cell death and its therapeutic implications [J]. Cytokine Growth Factor Rev , 2023 , 71-72 : 66 - 81 .
MANNICK J B , LAMMING D W . Targeting the biology of aging with mTOR inhibitors [J]. Nat Aging , 2023 , 3 ( 6 ): 642 - 660 .
GARGALIONIS A N , PAPAVASSILIOU K A , PAPAVASSILIOU A G . mTOR signaling: recent progress [J]. Int J Mol Sci , 2024 , 25 ( 5 ): 2587 .
DAI X , JIANG C , JIANG Q , et al . AMPK-dependent phosphorylation of the GATOR2 component WDR24 suppresses glucose-mediated mTORC1 activation [J]. Nat Metab , 2023 , 5 ( 2 ): 265 - 276 .
LAPLANTE M , SABATINI D M . mTOR signaling in growth control and disease [J]. Cell , 2012 , 149 ( 2 ): 274 - 293 .
DIBBLE C C , CANTLEY L C . Regulation of mTORC1 by PI3K signaling [J]. Trends Cell Biol , 2015 , 25 ( 9 ): 545 - 555 .
HOSIOS A M , WILKINSON M E , MCNAMARA M C , et al . mTORC1 regulates a lysosome-dependent adaptive shift in intracellular lipid species [J]. Nat Metab , 2022 , 4 ( 12 ): 1792 - 1811 .
SAXTON R A , SABATINI D M . mTOR signaling in growth, metabolism, and disease [J]. Cell , 2017 , 168 ( 6 ): 960 - 976 .
FU W , HALL M N . Regulation of mTORC2 signaling [J]. Genes (Basel) , 2020 , 11 ( 9 ): 1045 .
SZWED A , KIM E , JACINTO E . Regulation and metabolic functions of mTORC1 and mTORC2 [J]. Physiol Rev , 2021 , 101 ( 3 ): 1371 - 1426 .
SU K H , DAI C . mTORC1 senses stresses: Coupling stress to proteostasis [J]. Bioessays , 2017 , 39 ( 5 ): 10.1002/bies.201600268 .
JANG S , KWON E J , LEE J J . Rheumatoid arthritis: Pathogenic roles of diverse immune cells [J]. Int J Mol Sci , 2022 , 23 ( 2 ): 905 .
HU Z , LI Y , ZHANG L , et al . Metabolic changes in fibroblast-like synoviocytes in rheumatoid arthritis: state of the art review [J]. Front Immunol , 2024 , 15 : 1250884 .
DU H , ZHANG X , ZENG Y , et al . A novel phytochemical, DIM, inhibits proliferation, migration, invasion and TNF‑α induced inflammatory cytokine production of synovial fibroblasts from rheumatoid arthritis patients by targeting MAPK and AKT/mTOR signal pathway [J]. Front Immunol , 2019 , 10 : 1620 .
LIU S , MA H , ZHANG H , et al . Recent advances on signaling pathways and their inhibitors in rheumatoid arthritis [J]. Clin Immunol , 2021 , 230 : 108793 .
KARONITSCH T , KANDASAMY R K , KARTNIG F , et al . mTOR senses environmental cues to shape the fibroblast-like synoviocyte response to inflammation [J]. Cell Rep , 2018 , 23 ( 7 ): 2157 - 2167 .
WANG L , WU X , WAN Q , et al . Phloridzin reduces synovial hyperplasia and inflammation in rheumatoid arthritis rat by modulating mTOR pathway [J]. Int Immunopharmacol , 2024 , 133 : 111727 .
WANG L , WU X , WAN Q , et al . Phlorizin regulates synovial hyperplasia and inflammation in rats with rheumatoid arthritis by regulating the mTOR pathway [J]. In Vivo , 2024 , 38 ( 3 ): 1182 - 1191 .
MIZUSHIMA N , KOMATSU M . Autophagy: renovation of cells and tissues [J]. Cell , 2011 , 147 ( 4 ): 728 - 741 .
MAJUMDER P , SHUKLA C , ARYA A , et al . G-quadruplexes in MTOR and induction of autophagy [J]. Sci Rep , 2024 , 14 ( 1 ): 2525 .
BERNARD M , YANG B , MIGNEAULT F , et al . Autophagy drives fibroblast senescence through MTORC2 regulation [J]. Autophagy , 2020 , 16 ( 11 ): 2004 - 2016 .
SUN K , LUO J , GUO J , et al . The PI3K/AKT/mTOR signaling pathway in osteoarthritis: a narrative review [J]. Osteoarthritis Cartilage , 2020 , 28 ( 4 ): 400 - 409 .
POPOVA N V , JÜCKER M . The role of mTOR signaling as a therapeutic target in cancer [J]. Int J Mol Sci , 2021 , 22 ( 4 ): 1743 .
ZHAO J , JIANG P , GUO S , et al . Apoptosis, autophagy, NETosis, necroptosis, and pyroptosis mediated programmed cell death as targets for innovative therapy in rheumatoid arthritis [J]. Front Immunol , 2021 , 12 : 809806 .
YANG J , LIU J , LI J , et al . Celastrol inhibits rheumatoid arthritis by inducing autophagy via inhibition of the PI3K/AKT/mTOR signaling pathway [J]. Int Immunopharmacol , 2022 , 112 : 109241 .
葛晓琦 , 赵福涛 , 曲环汝 , 等 . 苏励从瘀论治类风湿关节炎的经验 [J]. 上海中医药杂志 , 2023 , 57 ( 7 ): 34 - 36 .
王淼 , 朱艳 . 艾灸治疗类风湿关节炎相关机制的研究进展 [J]. 风湿病与关节炎 , 2023 , 12 ( 10 ): 56 - 60 .
刘梨 , 张亮 , 艾坤 , 等 . 艾灸对佐剂性关节炎大鼠足趾滑膜组织自噬和凋亡的影响 [J]. 针刺研究 , 2023 , 48 ( 3 ): 253 - 258 .
郝锋 , 吴立斌 , 胡骏 , 等 . 艾灸对类风湿性关节炎模型大鼠足跖滑膜组织PI3K/Akt/mTOR信号通路的影响 [J]. 中国针灸 , 2020 , 40 ( 11 ): 1211 - 1216 .
HAO F , WANG Q , LIU L , et al . Effect of moxibustion on autophagy and the inflammatory response of synovial cells in rheumatoid arthritis model rat [J]. J Tradit Chin Med , 2022 , 42 ( 1 ): 73 - 82 .
苏虹 , 粟胜勇 , 羊璞 , 等 . 针灸治疗类风湿关节炎作用机制研究进展 [J]. 针刺研究 , 2023 , 48 ( 5 ): 500 - 507 .
苏成红 , 杜小正 , 方晓丽 , 等 . 热补针法对类风湿关节炎寒证家兔模型膝关节滑膜组织TLR4-MyD88-ERK1/2信号通路的影响 [J]. 北京中医药大学学报 , 2022 , 45 ( 7 ): 745 - 754 .
赵晨 , 张敏 , 朱艳 , 等 . 针刺调控PI3K/AKT/mTOR信号通路介导自噬保护佐剂性关节炎大鼠膝关节滑膜组织的研究 [J]. 针刺研究 , 2021 , 46 ( 12 ): 1016 - 1022 .
刘梨 , 周巍 , 黎铭玉 , 等 . 电针对类风湿关节炎大鼠踝关节滑膜组织自噬的影响 [J]. 针刺研究 , 2021 , 46 ( 12 ): 1023 - 1028 .
刘梨 , 龚志贤 , 李鑫 , 等 . 电针对类风湿性关节炎大鼠足趾滑膜组织PI3K/Akt/mTOR信号通路的影响 [J]. 时珍国医国药 , 2023 , 34 ( 4 ): 995 - 998 .
龙轶映 , 张亮 , 祁芳 , 等 . 电针对佐剂性关节炎大鼠滑膜组织中mTOR磷酸化水平的影响 [J]. 湖南中医药大学学报 , 2021 , 41 ( 12 ): 1881 - 1885 .
WANG J , CHEN Q , SHENG R , et al . Integration of transdermal chemistry and network pharmacology to decipher the mechanism of Shexiang Zhuifeng analgesic plaster to treat rheumatoid arthritis [J]. Phytomedicine , 2023 , 108 : 154507 .
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