NLRP3信号通路与痛风性关节炎的关系及中医药治疗的研究进展
The Relationship between NLRP3 Signaling Pathway and Gouty Arthritis and the Research Progress of Chinese Medicine Treatment
DOI: 10.12677/tcm.2025.142079, PDF,   
作者: 谭志康*：广西中医药大学研究生院，广西 南宁；朱 英#：广西中医药大学附属瑞康医院针灸科，广西 南宁
关键词: 痛风性关节炎；中医药；信号通路；研究进展；Gouty Arthritis； Chinese Medicine； Signal Pathway； Research Progress
摘要: 痛风性关节炎(GA)是人体内嘌呤代谢紊乱和(或)尿酸排泄异常引起的一组代谢性疾病。其发病原因多与饮食结构、蛋白质、糖、脂肪过多摄入有关。临床表现为关节红肿热痛，严重影响患者日常生活，因此对抗GA的药物等的研究较为迫切。西药治疗GA的药物如秋水仙碱等，虽能在短期内缓解疼痛，但是长期使用不良反应明显；与西药相比，中医药治疗GA疗效确切，安全性强，更易被患者接受。近年来，业界开展了大量研究探索中医药通过调控NOD样受体热蛋白结构域相关蛋白3 (NLRP3)信号通路治疗GA的作用机制。但目前尚缺乏关于中医药调控NLRP3通路进而治疗GA的全面系统的总结。本文简单阐述了NLRP3炎症信号通路与GA发生发展的关系和中医对痛风性关节炎的认识及诊疗经验，并总结了中药有效成分、中药复方及其制剂、中医外治干预NLRP3炎症小体治疗GA的最新研究报道，以期为GA发病机制及药物治疗的深入研究提供新思路，为临床上运用中医药防治GA提供依据。
Abstract: Gouty arthritis (GA) is a metabolic disorder of purine metabolism and/or abnormal uric acid excretion in the body. The etiology is related to excessive intake of diet, protein, sugar and fat. Clinical manifestations of joint redness, swelling, heat and pain, seriously affect the daily life of patients, so anti-GA drug research is more urgent. Western medicine for the treatment of GA, such as colchicine, can relieve pain in a short time, but the adverse reactions of long-term use are obvious. Compared with Western medicine, traditional Chinese medicine in treating GA is more effective, safer and more acceptable to patients. In recent years, many researches have been carried out to explore the mechanism of TCM treating GA by regulating the signal pathway of NOD receptor thermoprotein domain related protein 3 (NLRP3). However, there is still a lack of a comprehensive and systematic summary of TCM regulation of NLRP3 pathway to treat GA. In this paper, the relationship between NLRP3 inflammatory signaling pathway and the development of GA, the understanding of TCM and the experience of diagnosis and treatment of gouty arthritis were briefly discussed. And it summarized the latest research reports on the effective components of Chinese herbal medicine, Chinese herbal compound and its preparation, TCM external treatment intervention NLRP3 inflammatory body treatment of GA. It is expected to provide a new idea for the further study of pathogenesis and drug treatment of GA, and provide a basis for the prevention and treatment of GA with TCM.
文章引用：谭志康, 朱英. NLRP3信号通路与痛风性关节炎的关系及中医药治疗的研究进展[J]. 中医学, 2025, 14(2): 530-538. https://doi.org/10.12677/tcm.2025.142079

参考文献

[1] Schlesinger, N. (2011) Difficult-to-Treat Gouty Arthritis. Drugs, 71, 1413-1439. [Google Scholar] [CrossRef] [PubMed]
[2] Mbuyi, N. and Hood, C. (2020) An Update on Gout Diagnosis and Management for the Primary Care Provider. The Nurse Practitioner, 45, 16-25. [Google Scholar] [CrossRef] [PubMed]
[3] Serafini, T.A. and Emerling, D.E. (2010) Tranilast Suppresses Inflammation Induced by Monosodium Urate (MSU) Crystals in Vivo. Annals of the Rheumatic Diseases, 69, 664.
[4] Mandal, A.K., Mercado, A., Foster, A., Zandi-Nejad, K. and Mount, D.B. (2017) Uricosuric Targets of Tranilast. Pharmacology Research & Perspectives, 5, e00291. [Google Scholar] [CrossRef] [PubMed]
[5] Heitel, P., Gellrich, L., Heering, J., Goebel, T., Kahnt, A., Proschak, E., et al. (2018) Urate Transporter Inhibitor Lesinurad Is a Selective Peroxisome Proliferator-Activated Receptor γ Modulator (sPPARγM) in Vitro. Scientific Reports, 8, Article No. 13554. [Google Scholar] [CrossRef] [PubMed]
[6] Mandal, A., Emerling, D., Serafini, T., et al. (2010) Tranilast Inhibits Urate Transport Mediated by URAT1 and GLUT9. Arthritis & Rheumatology, 62, 164.
[7] Yu, C., Zhang, C., Kuang, Z. and Zheng, Q. (2020) The Role of NLRP3 Inflammasome Activities in Bone Diseases and Vascular Calcification. Inflammation, 44, 434-449. [Google Scholar] [CrossRef] [PubMed]
[8] Tseng, H., Samuel, S.G., Schroder, K., Lévesque, J. and Alexander, K.A. (2022) Inflammasomes and the IL-1 Family in Bone Homeostasis and Disease. Current Osteoporosis Reports, 20, 170-185. [Google Scholar] [CrossRef] [PubMed]
[9] 唐秀松, 赵心怡, 陈静, 等. 基于细胞焦亡理论探讨中医药防治类风湿关节炎研究进展[J]. 中国实验方剂学杂 志, 2022, 28(19): 231-240.
[10] Carneiro, L., Magalhaes, J., Tattoli, I., Philpott, D. and Travassos, L. (2007) Nod‐Like Proteins in Inflammation and Disease. The Journal of Pathology, 214, 136-148. [Google Scholar] [CrossRef] [PubMed]
[11] Ting, J.P., Lovering, R.C., Alnemri, E.S., Bertin, J., Boss, J.M., Davis, B.K., et al. (2008) The NLR Gene Family: A Standard Nomenclature. Immunity, 28, 285-287. [Google Scholar] [CrossRef] [PubMed]
[12] Davis, B.K., Wen, H. and Ting, J.P. (2011) The Inflammasome NLRs in Immunity, Inflammation, and Associated Diseases. Annual Review of Immunology, 29, 707-735. [Google Scholar] [CrossRef] [PubMed]
[13] Jo, E., Kim, J.K., Shin, D. and Sasakawa, C. (2015) Molecular Mechanisms Regulating NLRP3 Inflammasome Activation. Cellular & Molecular Immunology, 13, 148-159. [Google Scholar] [CrossRef] [PubMed]
[14] Bauernfeind, F.G., Horvath, G., Stutz, A., Alnemri, E.S., MacDonald, K., Speert, D., et al. (2009) Cutting Edge: NF-κB Activating Pattern Recognition and Cytokine Receptors License NLRP3 Inflammasome Activation by Regulating NLRP3 Expression. The Journal of Immunology, 183, 787-791. [Google Scholar] [CrossRef] [PubMed]
[15] Pu, Z.C., Han, C.Z., Zhang, W.W., et al. (2019) Systematic Understanding of the Mechanism and Effects of Arctigenin Attenuates Inflammation in Dextran Sulfate Sodium-Induced Acute Colitis through Suppression of NLPP3 Inflammasome by SIRT1. American Journal of Translational Research, 11, 3992-4009.
[16] Wang, T., Wang, J., Sun, T. and Li, Y. (2021) Amelioration of Juglanin against LPS-Induced Activation of NLRP3 Inflammasome in Chondrocytes Mediated by Sirt1. Inflammation, 44, 1119-1129. [Google Scholar] [CrossRef] [PubMed]
[17] Mangan, M.S.J., Olhava, E.J., Roush, W.R., Seidel, H.M., Glick, G.D. and Latz, E. (2018) Erratum: Targeting the NLRP3 Inflammasome in Inflammatory Diseases. Nature Reviews Drug Discovery, 17, 688-688. [Google Scholar] [CrossRef] [PubMed]
[18] Zhang, Q., Qing, Y., He, Y., Xie, W. and Zhou, J. (2017) Association of NLRP3 Polymorphisms with Susceptibility to Primary Gouty Arthritis in a Chinese Han Population. Clinical Rheumatology, 37, 235-244. [Google Scholar] [CrossRef] [PubMed]
[19] Renaudin, F., Orliaguet, L., Castelli, F., Fenaille, F., Prignon, A., Alzaid, F., et al. (2020) Gout and Pseudo-Gout-Related Crystals Promote Glut1-Mediated Glycolysis That Governs NLRP3 and Interleukin-1β Activation on Macrophages. Annals of the Rheumatic Diseases, 79, 1506-1514. [Google Scholar] [CrossRef] [PubMed]
[20] Li, X., Liu, Y., Luo, C. and Tao, J. (2022) Z1456467176 Alleviates Gouty Arthritis by Allosterically Modulating P2X7R to Inhibit NLRP3 Inflammasome Activation. Frontiers in Pharmacology, 13, Article 979939. [Google Scholar] [CrossRef] [PubMed]
[21] Reber, L.L., Marichal, T., Sokolove, J., Starkl, P., Gaudenzio, N., Iwakura, Y., et al. (2014) Contribution of Mast Cell-Derived Interleukin-1β to Uric Acid Crystal-Induced Acute Arthritis in Mice. Arthritis & Rheumatology, 66, 2881-2891. [Google Scholar] [CrossRef] [PubMed]
[22] 刘丽兰, 关宝生, 张淑红, 等. 痛风炎症反应中NLRP3炎性体的激活机制[J]. 中医临床研究, 2022, 14(6): 128-130, 136.
[23] Kong, R., Sun, L., Li, H. and Wang, D. (2021) The Role of NLRP3 Inflammasome in the Pathogenesis of Rheumatic Disease. Autoimmunity, 55, 1-7. [Google Scholar] [CrossRef] [PubMed]
[24] Wang, C.Y., Guo, X.C. and Zhang, J.P. (2015) Research Advances in NLRP3 Inflammasome-Related Regulatory Mechanisms. Acta Academiae Medicinae Sinicae, 37, 618-622.
[25] Church, L.D., Cook, G.P. and McDermott, M.F. (2008) Primer: Inflammasomes and Interleukin 1β in Inflammatory Disorders. Nature Clinical Practice Rheumatology, 4, 34-42. [Google Scholar] [CrossRef] [PubMed]
[26] 李满意, 娄玉钤. 痛风的源流及历史文献复习[J]. 风湿病与关节炎, 2018, 7(6): 57-62.
[27] 王宏, 李娟, 杨小黎, 等. 基于“阳化气, 阴成形”理论探讨痛风的中医证治[J]. 四川中医, 2020, 38(6): 50-53.
[28] 刘海云, 于静, 姜兆荣, 等. 金明秀教授从“毒”论治痛风性关节炎经验总结[J]. 世界中西医结合杂志, 2018, 13(8): 1072-1074, 1078.
[29] 冯波, 陆定其, 胡文秀, 等. 王新昌运用温法治疗痛风经验介绍[J]. 新中医, 2020, 52(15): 198-200.
[30] 朴勇洙, 张京, 任慧, 等. 国医大师卢芳运用丹溪痛风方治疗痛风经验[J]. 浙江中医药大学学报, 2020, 44(8): 715-718.
[31] 国家中医药管理局发布中华人民共和国中医药行业标准——《中医病证诊断疗效标准》[J]. 中医药管理杂志, 1994(6): 2.
[32] 李壮, 侯堃. 316例男性急性痛风性关节炎中医证候分类研究[J]. 中医杂志, 2019, 60(1): 47-50.
[33] 唐兆安, 王莘智. 从肝论治痛风[J]. 中医研究, 2019, 32(5): 4-5.
[34] 张艳珍, 张红红, 王洁, 等. 1张艳珍分期论治痛风性关节炎的经验总结[J]. 中国当代医药, 2022, 29(29): 123-126.
[35] 王耀光, 赵景峰, 张诗元, 等. 王耀光教授治疗痛风性关节炎临床经验总结[J]. 天津中医药, 2022, 39(6): 706-709.
[36] 仇湘中, 沈琳玲, 戎宽, 等. 仇湘中教授治疗痛风性关节炎的经验总结[J]. 中国中医骨伤科杂志, 2022, 30(4): 79-81.
[37] 袁飞侠, 梅晴晴, 张华东, 等. 李济仁治疗痛风性关节炎经验总结与延展[J]. 北京中医药, 2021, 40(4): 334-337.
[38] 黄宝怡, 叶仁群, 梁奇参. 苓降酸煮散联合非布司他片治疗脾虚湿蕴型高尿酸血症临床疗效观察[J]. 广州中医药大学学报, 2022, 39(12): 2793-2798.
[39] 孙淳, 王秀娟, 刘华一, 等. 运脾化浊法治疗脾虚型高尿酸血症回顾性研究[J]. 安徽中医药大学学报, 2021, 40(1): 38-42.
[40] 徐熠, 徐玲玲, 刘静, 等. 中药治疗慢性痛风性关节炎的规律及其Logistic回归分析[J]. 世界临床药物, 2013, 34(8): 469-471.
[41] 佟金秋, 马宝东, 陈岩松. 痛风内治法用药规律系统综述[J]. 实用中医内科杂志, 2013, 27(10): 1-2.
[42] 那莎, 段陈方圆, 王璐, 等. 牛膝总皂苷对大鼠急性痛风性关节炎的防治作用及机制研究[J]. 中国临床药理学与治疗学, 2017, 22(9): 966-971.
[43] 孙雪莲, 刘渊, 周红海. 牛膝总皂苷对兔膝骨关节炎软骨组织形态变化及关节液中IL-1β、TGF-β1含量的影响[J]. 中药新药与临床药理. 2016, 27(3): 321-326.
[44] 马锐, 吴胜本. 中药黄酮类化合物药理作用及作用机制研究进展[J]. 中国药物警戒, 2013, 10(5): 286-290.
[45] 金晓敏, 张晓熙, 郭璐, 等. 基于NLRP3炎性体轴探讨土茯苓总黄酮对痛风性关节炎的作用和机制[J]. 中国实验方剂学杂志, 2018, 24(4): 90-95.
[46] 马天红, 盛涛, 田崇梅, 等 . 虎杖醇提物通过 NLRP3/ASC/caspase-1轴干预小鼠急性痛风性关节炎的作用研究[J]. 中国中药杂志, 2019, 44(3): 546-552.
[47] 元明慧, 姜禹辰, 廉丽花, 等. 白芷提取物及其活性成分欧前胡素改善痛风性关节炎[J]. 中国药理学通报, 2022, 38(9): 1416-1420.
[48] 范为民. 通痹七物方对痛风性关节炎NLRP3炎症小体、线粒体自噬蛋白的影响[J]. 中药新药与临床药理, 2020, 31(7): 769-774.
[49] 郭玉星, 熊辉, 易法银, 等. 蠲痹历节清方对痛风细胞模型中PPARγ、TLR4、NF-κB的影响[J]. 世界科学技术-中医药现代化, 2019, 21(12): 2825-2830.
[50] 康佳莹, 吴芸, 顾文燕. 加味黄芪桂枝五物汤对急性痛风性关节炎大鼠NLRP3、IL-33和TGF-β1表达的影响[J]. 中国中医急症, 2019, 28(11): 1989-1992.
[51] 张晓熙, 邢梦雨, 赵鑫钰, 等. 基于NLRP3炎性体轴和NF-κB信号通路探讨加味三妙丸防治痛风性关节炎的作用及机制[J]. 浙江中医药大学学报, 2019, 43(10): 1130-1137.
[52] Richette, P., Doherty, M., Pascual, E., Barskova, V., Becce, F., Castaneda, J., et al. (2020) 2018 Updated European League against Rheumatism Evidence-Based Recommendations for the Diagnosis of Gout. Annals of the Rheumatic Diseases, 79, 31-38. [Google Scholar] [CrossRef] [PubMed]
[53] 张慧森, 刘健, 温石磊, 等. 温针灸治疗膝关节痛风性关节炎湿热蕴结证患者的疗效及对关节疼痛、关节功能和血清炎症指标的影响[J]. 河北中医, 2021, 43(7): 1170-1173.
[54] 肖艺, 周芬, 宋清, 等. 针刺联合中药外敷治疗急性痛风 性关节炎湿热痹阻证的疗效观察[J]. 上海针灸杂志, 2022, 41(1): 71-76.
[55] 位会娜, 曾丹怡, 尹诚语, 等. 电针干预急性痛风性关节炎小鼠NLRP3表达及镇痛作用研究[J]. 中国疼痛医学杂志, 2023, 29(4): 249-257.
[56] 谯童茜, 唐成林, 邱丽针, 等. 基于NLRP3炎性小体通路探讨电针对急性痛风性关节炎大鼠组织蛋白酶B的影响[J]. 针刺研究, 2021, 46(4): 295-300.
[57] 贺前松, 马萍, 陈瑶, 等. 微创针刀联合rHuEPO注射治疗痛风性关节炎的临床疗效及对TGF-1、NLRP3水平的影响[J]. 中国老年学杂志, 2019, 39(22): 5540-5544.