[关键词]
[摘要]
痛风性关节炎(gouty arthritis,GA)是一类因自身免疫反应而形成的炎症性疾病,其发病机制复杂。研究发现,由尿酸长期升高形成的尿酸钠(monosodium urate,MSU)晶体对GA形成起到了极其重要的作用。MSU晶体可通过诱导免疫反应促使关节组织中炎症、氧化应激(oxidative stress,OS)、中性粒细胞外陷阱、细胞凋亡以及巨噬细胞极化等形成,此类免疫反应的形成会对关节的细胞及组织造成严重损害,进一步诱导GA的发生。现有研究表明,“自噬-GA”干预机制与中医“正邪相争”理论存在高度吻合,激活自噬可分解代谢受损细胞及蛋白质、维持细胞稳态、促进腺嘌呤核苷三磷酸产生提供能量等方式激发人体正气,以发挥正气自我调节、自我修复、抵御病邪的作用,正盛则邪却,从而缓解GA病情。大量中医药研究证明,如利用二氢丹参酮I、穿龙薯蓣总皂苷等中药活性提取物以及独活寄生汤、当归四逆汤等中药复方基于自噬途径干预GA后,可有效阻止上述免疫反应,显著改善GA关节组织的炎症及OS状态,减少关节组织的疼痛及肿胀,揭示中医药干预自噬或是未来开发治疗GA的重要途径之一。基于此,详细综述了自噬在GA中的作用机制以及潜在的干预靶点,旨在为GA开发治疗手段提供新的有效思路。
[Key word]
[Abstract]
Gouty arthritis (GA) is an inflammatory disease arising from autoimmune responses, with a complex pathogenesis. Research indicates that monosodium urate (MSU) crystals, formed by prolonged elevated uric acid levels, play a crucial role in the development of GA. MSU crystals can induce immune responses that promote inflammation, oxidative stress (OS), neutrophil extracellular traps, apoptosis, and macrophage polarization within joint tissues. These immune responses cause severe damage to joint cells and tissues, further inducing the onset of GA. Existing research indicates that the “autophagy-gout” intervention mechanism aligns closely with the traditional Chinese medicine (TCM) theory of “struggle between healthy qi and pathogenic qi”. Activating autophagy stimulates the body's righteous energy by degrading damaged cells and proteins, maintaining cellular homeostasis, and promoting adenosine triphosphate production for energy supply. This enables the righteous energy to self-regulate, self-repair, and resist pathogenic factors, thereby improving gout conditions. Extensive TCM research demonstrates that active herbal extracts such as dihydrodanshikeniol I and diosgenin total saponins, along with TCM formulas like Duhuo Jisheng Decoction and Danggui Sini Decoction, can effectively inhibit the aforementioned immune responses, significantly alleviate inflammation and OS in GA joint tissues, and reduce joint pain and swelling. This suggests that TCM intervention targeting autophagy may represent a promising therapeutic avenue for GA. Based on this, this paper details the mechanisms of autophagy in GA and potential intervention targets, aiming to provide new effective approaches for developing GA treatment strategies.
[中图分类号]
R284.1
[基金项目]
第五批全国中医临床优秀人才研修项目(国中医药人教函[2022]1号);第六批四川省名中医传承工作室建设项目——四川省名中医高泓传承工作室(川中医药办发[2023]36号);成都市卫生健康委员会-成都中医药大学委校联合创新基金(WXLH202403014);成都中医药大学附属医院省重点实验室专项基金(23SZ03)