Wang Hao, Liu Mingxuan, Xie Cunxiang, Zhao Luming, Wang Hailong
Department of Rheumatology and Immunology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
J Inflamm Res. 2025 Jun 19;18:8141-8151. doi: 10.2147/JIR.S525351. eCollection 2025.
Gout is an inflammatory arthritis caused by the deposition of monosodium urate crystals in joints, severely affecting patients' health. However, the management of gout remains suboptimal. Current clinical treatments primarily focus on anti-inflammatory and urate-lowering medications, which are associated with potential toxicities and other limitations. Chronotherapy, based on chronobiology, has gradually demonstrated unique advantages in the treatment of various inflammatory diseases and holds promise as a safer and more effective new strategy for treating gout.
This article aims to explore the biological mechanisms underlying the circadian rhythmicity of gout flares and the potential role of chronobiology-based therapeutic approaches in the treatment of gout.
The referenced research articles were sourced from major scientific databases, including Google Scholar, PubMed, and Web of Science. The search strategy employed keywords such as "Gout", "Circadian rhythm", and "Chronobiology".
As the core inflammatory signaling pathway in gout, the NF-κB signaling pathway exhibits strong circadian rhythmicity under the regulation of circadian clock genes such as REV-ERBα. The gut microbiota may induce circadian oscillations in serum uric acid(UA) levels and trigger the rhythmic occurrence of gout flares by influencing the expression of REV-ERBα, rhythmically activating the NF-κB inflammatory signaling pathway, and altering the abundance. Therefore, the gut microbiota/REV-ERBα/NF-κB axis may be the potential biological mechanism underlying the circadian rhythmicity of gout flares.
From the perspective of chronobiology, a chronobiology-based therapeutic approach targeting the gut microbiota/REV-ERBα/NF-κB axis-such as adjusting medication timing, dietary interventions to modulate the gut microbiota, and targeted pharmacological agents-holds promise as a novel clinical strategy for treating gout and has potential clinical value. However, the conclusions drawn in this paper lack scientific experimental and clinical validation. Therefore, exploring this therapeutic approach represent a key and promising direction for treating gout.
痛风是一种由单钠尿酸盐晶体在关节中沉积引起的炎症性关节炎,严重影响患者健康。然而,痛风的管理仍不尽人意。目前的临床治疗主要集中在抗炎和降尿酸药物上,这些药物存在潜在毒性和其他局限性。基于时间生物学的时间疗法在各种炎症性疾病的治疗中逐渐显示出独特优势,有望成为治疗痛风的更安全、更有效的新策略。
本文旨在探讨痛风发作昼夜节律的生物学机制以及基于时间生物学的治疗方法在痛风治疗中的潜在作用。
参考的研究文章来自主要科学数据库,包括谷歌学术、PubMed和科学网。搜索策略使用了“痛风”、“昼夜节律”和“时间生物学”等关键词。
作为痛风中的核心炎症信号通路,核因子κB(NF-κB)信号通路在诸如视黄酸受体相关孤儿受体α(REV-ERBα)等生物钟基因的调控下表现出强烈的昼夜节律性。肠道微生物群可能诱导血清尿酸(UA)水平的昼夜振荡,并通过影响REV-ERBα的表达、有节奏地激活NF-κB炎症信号通路以及改变丰度来触发痛风发作的节律性发生。因此,肠道微生物群/REV-ERBα/NF-κB轴可能是痛风发作昼夜节律的潜在生物学机制。
从时间生物学的角度来看,一种基于时间生物学的针对肠道微生物群/REV-ERBα/NF-κB轴的治疗方法,如调整用药时间、通过饮食干预调节肠道微生物群以及使用靶向药物,有望成为治疗痛风的一种新的临床策略,具有潜在的临床价值。然而,本文得出的结论缺乏科学实验和临床验证。因此,探索这种治疗方法是治疗痛风的一个关键且有前景的方向。