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天津中医药大学 中药学院,天津 301617
Received:25 January 2022,
Published Online:08 March 2022,
Published:20 October 2022
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贾子跃,张少卓.调控肿瘤坏死因子及其信号通路的中药治疗骨性关节炎的研究进展[J].中国实验方剂学杂志,2022,28(20):250-257.
JIA Ziyue,ZHANG Shaozhuo.Chinese Medicine in Treatment of Osteoarthritis by Regulating Tumor Necrosis Factor and Signaling Pathways: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(20):250-257.
贾子跃,张少卓.调控肿瘤坏死因子及其信号通路的中药治疗骨性关节炎的研究进展[J].中国实验方剂学杂志,2022,28(20):250-257. DOI: 10.13422/j.cnki.syfjx.20220909.
JIA Ziyue,ZHANG Shaozhuo.Chinese Medicine in Treatment of Osteoarthritis by Regulating Tumor Necrosis Factor and Signaling Pathways: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(20):250-257. DOI: 10.13422/j.cnki.syfjx.20220909.
骨性关节炎(OA),又名退行性骨性关节炎。其主要临床表现为关节疼痛、肿胀及功能障碍。随着现代社会人口老龄化程度的加重,其发病率在全世界范围内呈逐年上升的趋势,已经成为使中老年人生活质量下降、甚至残疾的主要疾病之一。现代医学对OA的研究表明,由激活的巨噬细胞和(或)滑膜细胞产生的肿瘤坏死因子-
α
(TNF-
α
),是OA炎症反应的始动因子,能与多个信号传导通路协同作用,被认为是OA病程中促进软骨基质降解及关节软骨破坏的最重要的细胞因子和炎症介质之一,在OA的病程中发挥着关键的核心作用。中医药在中医基础理论指导下,遵循以人为本、辨证论治的原则对OA进行个体化治疗,具有多靶点、高疗效和低不良反应的显著优势。近年来探讨中药及其有效成分抗OA的具体作用机制成为研究热点。该文阐述了TNF-
α
及其信号传导通路在OA病程中的作用,并分析总结作用于TNF-
α
及其信号传导通路的中药治疗OA的现代医学研究进展,旨在为中医药抗OA的临床治疗、基础研究及靶向药物的研发提供一定的参考依据。
Osteoarthritis (OA) is also known as degenerative arthritis with prominent clinical manifestations of joint pain, joint swelling, and loss of mobility. With the aggravation of population aging in modern society, its incidence is increasing year by year worldwide, and it has become one of the main diseases that reduce the quality of life of middle-aged and elderly people and even lead to disability. Modern medical research on OA has shown that tumor necrosis factor-
α
(TNF-
α
) produced by activated macrophages and/or synoviocytes is the initiator of OA inflammatory response and can interact with multiple signal transduction pathways. It is considered to be one of the most important cytokines and inflammatory mediators that promote the degradation of cartilage matrix and the destruction of articular cartilage in the course of OA, and plays a key role in the course of OA. Under the guidance of the basic theories of traditional Chinese medicine (TCM), Chinese medicine provides individualized treatment of OA following the principle of people-oriented, syndrome differentiation and treatment, and has the significant advantages of multiple targets, high efficacy, and low toxicity. In recent years, it has become a research hotspot to explore the specific mechanism of Chinese medicine and its active ingredients in the treatment of OA. This study described the role of TNF-
α
and its signal transduction pathways in the course of OA and reviewed the modern medical research advances in Chinese medicine acting on TNF-
α
and its signal transduction pathways in the treatment of OA, providing a certain reference basis for the clinical treatment of OA, basic research, and development of targeted drugs.
王斌 , 邢丹 , 董圣杰 , 等 . 中国膝骨关节炎流行病学和疾病负担的系统评价 [J]. 中国循证医学杂志 , 2018 , 18 ( 2 ): 134 - 142 .
中华医学会骨科学分会关节外科学组 . 骨关节炎诊疗指南(2018年版) [J]. 中华骨科杂志 , 2018 , 38 ( 12 ): 705 - 715 .
李涛 . 辨病辨证相结合治疗膝骨关节炎临床观察 [D]. 济南 : 山东中医药大学 , 2011 .
叶芳 , 叶胥华 , 叶欣 . 辨证施治膝骨性关节炎81例 [J]. 陕西中医 , 2005 ( 12 ): 1302 - 1303 .
邓伟 . 补脾益肾化瘀法治疗膝骨关节炎 [J]. 中药材 , 2003 , 26 ( 7 ): 535 - 537 .
梁桂洪 , 梁祖建 , 林勇凯 , 等 . 补肾活血中药对比塞来昔布治疗膝骨性关节炎疗效与安全性的Meta分析 [J]. 中国药房 , 2016 , 27 ( 27 ): 3810 - 3813,3814 .
吴泳昕 , 肖泓 , 吴生元 . 补中桂枝汤治疗退行性骨关节病83例 [J]. 四川中医 , 2002 , 20 ( 2 ): 63 - 64 .
陈广祯 , 李心沁 , 梁安民 . 从瘀血痰湿论治膝关节骨性关节炎58例 [J]. 山东中医药大学学报 , 1998 ( 1 ): 31 - 32 .
吕国光 . 连建伟教授运用独活寄生汤治疗痹症经验 [J]. 浙江中西医结合杂志 , 2009 , 19 ( 11 ): 687 .
邓平征 , 夏启水 , 陶丽娟 . 中药独活寄生汤加减对膝骨性关节炎患者的疗效及其对炎症因子水平的影响 [J]. 抗感染药学 , 2017 , 14 ( 7 ): 1393 - 1396 .
WESTACOTT C I , SHARIF M . Cytokines in osteoarthritis:Mediators or markers of joint destruction? [J]. Semin Arthritis Rheum , 1996 , 25 ( 4 ): 254 - 272 .
CARSWELL E A , OLD L J , KASSEL R L , et al . An endotoxin-induced serum factor that causes necrosis of tumors [J]. Proc Natl Acad Sci U S A , 1975 , 72 ( 9 ): 3666 - 3670 .
冯速 , 邱樊 , 张壮壮 , 等 . 肿瘤坏死因子家族及其相关药物的研究进展 [J]. 药学进展 , 2016 , 40 ( 4 ): 284 - 292 .
AYUSO E , MINGOZZI F , BOSCH F.Production , purification and characterization of adeno-associated vectors [J]. Curr Gene Ther , 2010 , 10 ( 6 ): 423 - 436 .
冯馨锐 , 崔雨舒 , 何志涛 , 等 . 肿瘤坏死因子- α 的生物学功能研究进展 [J]. 吉林医药学院学报 , 2019 , 40 ( 1 ): 66 - 68 .
KAPOOR M , MARTEL-PELLETIER J , LAJEUNESSE D , et al . Role of proinflammatory cytokines in the pathophysiology of osteoarthritis [J]. Nat Rev Rheumatol , 2011 , 7 ( 1 ): 33 - 42 .
ROMAN-BLAS J A , JIMENEZ S A . NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis [J]. Osteoarthr Cartil , 2006 , 14 ( 9 ): 839 - 848 .
MARCU K B , OTERO M , OLIVOTTO E , et al . NF-kappaB signaling:Multiple angles to target OA [J]. Curr Drug Targets , 2010 , 11 ( 5 ): 599 - 613 .
GUICCIARDI M E , GORES G J . Life and death by death receptors [J]. FASEB J , 2009 , 23 ( 6 ): 1625 - 1637 .
GOUKASSIAN D A , QIN G , DOLAN C , et al . Tumor necrosis factor-alpha receptor p75 is required in ischemia-induced neovascularization [J]. Circulation , 2007 , 115 ( 6 ): 752 - 762 .
MARCHETTI L , KLEIN M , SCHLETT K , et al . Tumor necrosis factor (TNF)-mediated neuroprotection against glutamate-induced excitotoxicity is enhanced by N -methyl- D -aspartate receptor activation.Essential role of a TNF receptor 2-mediated phosphatidylinositol 3-kinase-dependent NF-kappa B pathway [J]. J Biol Chem , 2004 , 279 ( 31 ): 32869 - 32881 .
CHEN X , BÄUMEL M , MÄNNEL D N , et al . Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4 + CD25 + T regulatory cells [J]. J Immunol , 2007 , 179 ( 1 ): 154 - 161 .
SINGH U , KUMAR A , SINHA R , et al . Calreticulin transacetylase catalyzed modification of the TNF-alpha mediated pathway in the human peripheral blood mononuclear cells by polyphenolic acetates [J]. Chem Biol Interact , 2010 , 185 ( 3 ): 263 - 270 .
LI X , HUANG Q , ONG C N , et al . Chrysin sensitizes tumor necrosis factor-alpha-induced apoptosis in human tumor cells via suppression of nuclear factor-kappaB [J]. Cancer Lett , 2010 , 293 ( 1 ): 109 - 116 .
陈根强 , 许慧娟 , 汪志明 , 等 . 骨性关节炎患者中血清与关节液的炎性因子水平变化及意义 [J]. 武汉大学学报:医学版 , 2014 , 35 ( 1 ): 110 - 113 .
高坤 , 陈大宇 , 张勇 , 等 . 牛膝醇提物调控滑膜成纤维细胞外泌体抑制软骨细胞外基质降解 [J]. 中国组织工程研究 , 2021 , 25 ( 23 ): 3636 - 3640 .
JOOSTEN L A , HELSEN M M , VAN DE LOO F A , et al . Anticytokine treatment of established type Ⅱcollagen-induced arthritis in DBA/1 mice:A comparative study using anti-TNFalpha,anti-IL-1alpha/beta and IL-1Ra [J]. Arthritis Rheum , 2008 , 58 ( 2 Suppl ): S110 - 122 .
GUERNE P A , CARSON D A , LOTZ M . IL-6 production by human articular chondrocytes.Modulation of its synthesis by cytokines,growth factors,and hormones in vitro [J]. J Immunol , 1990 , 144 ( 2 ): 499 - 505 .
LOTZ M , TERKELTAUB R , VILLIGER P M . Cartilage and joint inflammation.Regulation of IL-8 expression by human articular chondrocytes [J]. J Immunol , 1992 , 148 ( 2 ): 466 - 473 .
VILLIGER P M , TERKELTAUB R , LOTZ M . Monocyte chemoattractant protein-1 (MCP-1) expression in human articular cartilage.Induction by peptide regulatory factors and differential effects of dexamethasone and retinoic acid [J]. J Clin Invest , 1992 , 90 ( 2 ): 488 - 496 .
SAKLATVALA J . Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage [J]. Nature , 1986 , 322 ( 6079 ): 547 - 549 .
SÉGUIN C A , BERNIER S M . TNFalpha suppresses link protein and type Ⅱ collagen expression in chondrocytes:Role of MEK1/2 and NF-kappaB signaling pathways [J]. J Cell Physiol , 2003 , 197 ( 3 ): 356 - 369 .
LEFEBVRE V , PEETERS-JORIS C , VAES G . Modulation by interleukin 1 and tumor necrosis factor alpha of production of collagenase,tissue inhibitor of metalloproteinases and collagen types in differentiated and dedifferentiated articular chondrocytes [J]. Biochim Biophys Acta , 1990 , 1052 ( 3 ): 366 - 378 .
REBOUL P , PELLETIER J P , TARDIF G , et al . The new collagenase,collagenase-3,is expressed and synthesized by human chondrocytes but not by synoviocytes.A role in osteoarthritis [J]. J Clin Invest , 1996 , 97 ( 9 ): 2011 - 2019 .
ZHAO Y P , LIU B , TIAN Q Y , et al . Progranulin protects against osteoarthritis through interacting with TNF- α and β -catenin signalling [J]. Ann Rheum Dis , 2015 , 74 ( 12 ): 2244 - 2253 .
GOLDRING M B , OTERO M , PLUMB D A , et al . Roles of inflammatory and anabolic cytokines in cartilage metabolism:Signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis [J]. Eur Cell Mater , 2011 , 21 : 202 - 220 .
KOOPMAN W J , MORELAND L W . Arthritis and allied conditions:A textbook of rheumatology 15th edition [M]. USA : Lippincott Williams & Wilkins , 2004 : 2199 - 2226 .
MATHY-HARTERT M , HOGGE L , SANCHEZ C , et al . Interleukin-1beta and interleukin-6 disturb the antioxidant enzyme system in bovine chondrocytes:A possible explanation for oxidative stress generation [J]. Osteoarthr Cartil , 2008 , 16 ( 7 ): 756 - 763 .
SCOTT J L , GABRIELIDES C , DAVIDSON R K , et al . Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease [J]. Ann Rheum Dis , 2010 , 69 ( 8 ): 1502 - 1510 .
MAGNANO M D , CHAKRAVARTY E F , BROUDY C , et al . A pilot study of tumor necrosis factor inhibition in erosive/inflammatory osteoarthritis of the hands [J]. J Rheumatol , 2007 , 34 ( 6 ): 1323 - 1327 .
CHAN E K , CERIBELLI A , SATOH M . MicroRNA-146a in autoimmunity and innate immune responses [J]. Ann Rheum Dis , 2013 , 72 ( Suppl 2 ):ii90-ii95.
林平冬 , 翁霞萍 , 刘发元 , 等 . 牛膝有效成分防治骨关节炎的作用机制探讨 [J]. 风湿病与关节炎 , 2015 , 4 ( 2 ): 56 - 59 .
魏锦强 , 孙赫 , 曹学伟 , 等 . 牛膝治疗骨关节炎作用机制的网络药理学探讨 [J]. 中药新药与临床药理 , 2020 , 31 ( 9 ): 1052 - 1060 .
ZHUANG Z , YE G , HUANG B . Kaempferol alleviates the interleukin-1 β -induced inflammation in rat osteoarthritis chondrocytes via suppression of NF- κ B [J]. Med Sci Monit , 2017 , 23 : 3925 - 3931 .
周运江 , 王虎 , 李丽 , 等 . 山柰酚对脂多糖诱导的肥大细胞炎症反应的抑制作用 [J]. 药学学报 , 2015 , 50 ( 6 ): 702 - 707 .
卢伟达 , 任杰 , 张志宏 , 等 . 单味中药治疗骨质疏松症及骨关节炎研究进展 [J]. 河南中医 , 2021 , 41 ( 3 ): 478 - 482 .
章晓云 , 张驰 , 宋世雷 , 等 . 基于网络药理学和蛋白模块分析淫羊藿治疗骨关节炎的作用与机制 [J]. 中国组织工程研究 , 2020 , 24 ( 17 ): 2660 - 2666 .
吴迎春 , 吕刚 , 依力潘·凯赛尔 , 等 . 淫羊藿总黄酮联合硫酸氨基葡萄糖对膝骨关节炎疗效临床研究 [J]. 中国骨质疏松杂志 , 2017 , 23 ( 9 ): 1195 - 1198 .
秦丰伟 , 黄荷 , 焦锋 , 等 . 淫羊藿苷和骨髓间充质干细胞共育液对兔骨关节炎模型关节液中IL-1、TNF- α 、IL-10、MMP-3表达的影响 [J]. 实用医学杂志 , 2018 , 34 ( 17 ): 2876 - 2879 .
余永林 , 吴家顺 , 热合米丁·艾买提 , 等 . 淫羊藿甙干预脂肪间充质干细胞修复膝骨性关节炎的作用及相关机制研究 [J]. 中国免疫学杂志 , 2021 , 37 ( 3 ): 301 - 306 .
MI B , WANG J , LIU Y , et al . Icariin activates autophagy via down-regulation of the NF- κ B signaling-mediated apoptosis in chondrocytes [J]. Front Pharmacol , 2018 , 9 : 605 .
金剑飞 , 何维英 , 周钰龙 . 淫羊藿总黄酮对膝关节骨性关节炎大鼠核因子- κ B通路的影响 [J]. 中国中医骨伤科杂志 , 2020 , 28 ( 3 ): 5 - 9,14 .
CHEN M P , YANG S H , CHOU C H , et al . The chondroprotective effects of ferulic acid on hydrogen peroxide-stimulated chondrocytes:Inhibition of hydrogen peroxide-induced pro-inflammatory cytokines and metalloproteinase gene expression at the mRNA level [J]. Inflamm Res , 2010 , 59 ( 8 ): 587 - 595 .
ZHOU Y , MING J , LI Y , et al . Ligustilide attenuates nitric oxide-induced apoptosis in rat chondrocytes and cartilage degradation via inhibiting JNK and p38 MAPK pathways [J]. J Cell Mol Med , 2019 , 23 ( 5 ): 3357 - 3368 .
郭光鑫 , 孙颖 , 栾海鹏 , 等 . 基于网药学方法探究透脓散治疗慢性骨髓炎的分子作用机制 [J]. 世界中医药 , 2022 , 17 ( 6 ): 773 - 778 .
YIN Y , LIU X , LIU J , et al . Beta-sitosterol and its derivatives repress lipopolysaccharide/d-galactosamine-induced acute hepatic injury by inhibiting the oxidation and inflammation in mice [J]. Bioorg Med Chem Lett , 2018 , 28 ( 9 ): 1525 - 1533 .
GABAY O , SANCHEZ C , SALVAT C , et al . Stigmasterol:A phytosterol with potential anti-osteoarthritic properties [J]. Osteoarthritis Cartilage , 2010 , 18 ( 1 ): 106 - 116 .
HE L , PAN Y , YU J , et al . Decursin alleviates the aggravation of osteoarthritis via inhibiting PI3K-Akt and NF- κ B signal pathway [J]. Int Immunopharmacol , 2021 , 97 : 107657 .
SHI X , ZHANG H , HU Y , et al . Mechanism of Salviae Miltiorrhizae Radix et Rhizoma in the treatment of knee osteoarthritis based on network pharmacology [J]. Nat Prod Commun , 2020 , doi: 10.21203/rs.3.rs-75437/v1 http://dx.doi.org/10.21203/rs.3.rs-75437/v1 .
FEI J , LIANG B , JIANG C , et al . Luteolin inhibits IL-1 β -induced inflammation in rat chondrocytes and attenuates osteoarthritis progression in a rat model [J]. Biomed Pharmacother , 2019 , 109 : 1586 - 1592 .
TANG S , SHEN X Y , HUANG H Q , et al . Cryptotanshinone suppressed inflammatory cytokines secretion in RAW264.7 macrophages through inhibition of the NF- κ B and MAPK signaling pathways [J]. Inflammation , 2011 , 34 ( 2 ): 111 - 118 .
洪瑛 , 晏为华 , 刘修树 . 丹参酮Ⅱ A 下调NF- κ B信号通路发挥对IL-1 β 所致软骨细胞损伤的保护作用 [J]. 海峡药学 , 2021 , 33 ( 6 ): 4 - 8 .
庄园 . 丹参酮对膝骨性关节炎模型细胞活性及氧自由基代谢的影响 [D]. 广州 : 暨南大学 , 2007 .
陈辉文 . 新补骨脂异黄酮抑制破骨细胞分化、减轻小鼠去卵巢后骨质丢失的作用及机制研究 [D]. 上海 : 中国人民解放军海军军医大学 , 2021 .
陈卫衡 . 重视循证医学证据,规范膝骨关节炎中医诊疗 [J]. 中医正骨 , 2021 , 33 ( 4 ): 1 - 3 .
LIU F , WENG X , LIN P , et al . Duhuo Jisheng decoction inhibits endoplasmic reticulum stress in chondrocytes induced by tunicamycin through the downregulation of miR-34a [J]. Int J Mol Med , 2015 , 36 ( 5 ): 1311 - 1318 .
陈后煌 , 邵翔 , 叶蕻芝 , 等 . 独活寄生汤对脂多糖诱导的大鼠软骨细胞炎症模型IL-1 β 、TNF- α 表达的影响 [J]. 中华老年骨科与康复电子杂志 , 2017 , 3 ( 2 ): 77 - 84 .
许丽梅 , 李慧 , 许云腾 , 等 . 基于NF- κ B信号通路探讨独活寄生汤抑制脂多糖诱导的软骨细胞炎症反应的作用机制 [J]. 中医正骨 , 2019 , 31 ( 7 ): 9 - 14,20 .
吴广文 , 邱建清 , 刘淑如 , 等 . 独活寄生汤含药血清对大鼠退变软骨细胞TLR4/NF- κ B信号通路的影响 [J]. 亚太传统医药 , 2019 , 15 ( 11 ): 28 - 32 .
杜津莉 , 樊炜骏 , 李建 , 等 . 独活寄生汤含药血清对膝关节OA大鼠滑膜细胞TNF- α 、IL-6、IL-8、IL-10表达的影响及其机制 [J]. 山东医药 , 2017 , 57 ( 44 ): 14 - 17 .
金钟浦 . 痹祺胶囊联合玻璃酸钠关节腔注射对膝骨关节炎患者炎症反应及骨关节炎评分的影响 [J]. 药品评价 , 2020 , 17 ( 18 ): 31 - 33 .
吴沅皞 , 刘维 , 刘晓亚 , 等 . 痹祺胶囊对兔骨关节炎软骨代谢的作用研究 [J]. 中华中医药学刊 , 2010 , 28 ( 8 ): 1608 - 1610 .
刘丽娟 , 王允亮 , 许树青 , 等 . 靛玉红、色胺酮对LPS诱导RAW264.7炎症细胞模型的抗炎作用研究 [J]. 世界中西医结合杂志 , 2015 ( 8 ): 1069 - 1072 .
陶帅 . 基于天癸理论的补肾活血方治疗绝经后膝骨关节炎的疗效与机制 [D]. 南京 : 南京中医药大学 , 2021 .
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