P2X7R:急性痛风性关节炎可能的关键调控因子

翻译研究生：刘樱         校正：庞宇洁       审核:张莉芸

P2X7R: A potential key regulator of acute gouty arthritis

Abstract -IVES:Acute gouty arthritis is an inflammatory disease resulting from the precipitation of long-term hyperuricemia-induced monosodium urate (MSU) crystals in joints, which stimulates the production of interleukin-1beta (IL-1β) and initiates an inflammatory reaction. However, some patients having MSU crystals in the joints never develop acute gouty arthritis, indicating that other predisposing factors are required for the disease onset. This review described the mechanism of production of IL-1β by MSU crystals and other possible factors during a gout attack.METHODS:The relevant English literature on IL-1β secretion stimulated by MSU crystals and other possible factors during acute gouty arthritis flares was searched and carefully reviewed.RESULTS:MSU crystals lead to the onset of acute gouty arthritis mainly through the activation of Toll-like receptors (TLRs) and ACHT-LRR-PYD-containing protein 3 (NALP3) inflammasome signaling and downstream IL-1β production. The predisposing factors of acute gouty arthritis, such as strenuous exercise, cold, alcolholism, and overeating have a common characteristic inducing dramatic changes of adenosine triphosphate (ATP) in the body. The ATP changes can activate the purinergic receptor P2X ligand-gated ion channel 7 (P2X7R) signaling system to regulate IL-1β secretion.CONCLUSIONS:We hypothesize that acute gouty arthritis is induced by two synergistic effects; one is the stimulation of MSU crystals and the other is the activation of P2X7R signaling pathways by extracellular ATP changes, which together lead to the production of IL-1β and the initiation of acute gouty arthritis. This hypothesis will provide a new avenue for the prevention and treatment of acute gouty arthritis.

摘要 目的：急性痛风性关节炎是一种由于长期高尿酸血症导致尿酸盐结晶沉积在关节引起的炎性疾病。尿酸盐结晶刺激产生白细胞介素-1β（IL-1β），并启动炎症反应。然而，一些患者尿酸盐沉积在关节，但不会发展成急性痛风关节炎，这说明着痛风发作还有其他潜在的诱因。这篇文章主要描述了在急性痛风发作时尿酸结晶和其他可能的因素引起IL-1β的生成机制。方法：检索、复习有关急性痛风性关节炎发作时尿酸盐结晶和其他可能的因素刺激IL-1β产生的相关文献。结果：尿酸盐结晶导致急性痛风性关节炎发作主要通过激活Toll样抗体、ALP3信号系统，及下游的IL-1β而导致痛风发作。急性痛风性关节炎的诱因如剧烈运动、寒冷、喝酒、暴饮暴食，都会引起身体ATP剧烈变化。ATP的变化激活P2X7R信号系统从而导致IL-1β的生成。结论：我们推测急性痛风发作是由于两种因素协同作用导致的。一个是由于尿酸盐晶体的刺激，另一个是由于细胞基质外ATP的变化而引起P2X7R信号通路的激活，这两种因素共同导致了IL-1β的生成及急性痛风性关节炎的发作。这一假说为预防和治疗痛风性关节炎急性发作提供了新方法。