文献类型：期刊文献

中文题名：Nrf2及其相关信号通路在膝骨关节炎发病机制中研究

英文题名：Research progress of Nrf2 and its related signaling pathways in the pathogenesis of knee osteoarthritis

作者：邵鸿[1];赵继荣[1];李喜香[2];黄清杰[2];陈祁青[2]

第一作者：邵鸿

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃省中医院,甘肃兰州730050

第一机构：甘肃中医药大学

年份：2025

卷号：31

期号：11

起止页码：1656

中文期刊名：中国骨质疏松杂志

外文期刊名：Chinese Journal of Osteoporosis

收录：;北大核心:【北大核心2023】；

基金：甘肃省2021年度省级重点人才项目[甘组通字(2021)17号]。

语种：中文

中文关键词：膝骨关节炎;Nrf2信号通路;氧化应激;炎症;铁死亡

外文关键词：knee osteoarthritis;Nrf2 signaling pathway;oxidative stress;inflammation;iron death

摘要：膝骨关节炎(knee osteoarthritis,KOA)是一种以关节软骨退化、软骨下骨改变及滑膜炎症为主要特征,伴随关节疼痛和功能障碍的慢性退行性关节疾病。核转录因子红系2相关因子2(Nrf2)是细胞内的重要抗氧化调节因子,其通过调控下游抗氧化、抗炎和抗铁死亡基因的表达,在维持细胞氧化还原平衡和保护组织功能方面发挥关键作用。研究表明,Nrf2信号通路通过多种机制在KOA的发病中发挥保护作用,Nrf2激活后通过上调HO-1、NQO1、SOD等抗氧化酶的表达,减少ROS积累,缓解氧化应激,保护软骨细胞免受氧化损伤;Nrf2通过抑制NF-κB和NLRP3炎症小体的激活,减少促炎性因子(如IL-1β、TNF-α)的产生,减轻滑膜炎症和软骨退化;此外,Nrf2通过调节GPX4表达,抑制脂质过氧化和铁死亡,保护软骨细胞,进一步延缓KOA进展。该综述系统总结了Nrf2信号通路在KOA中抗氧化、抗炎和抗铁死亡具体机制,探讨其在KOA中的核心作用及治疗潜力,强调这些机制单独或相互作用对KOA的影响,为理解KOA的发病机制提供了新视角,为开发针对KOA的多靶点干预策略和高效治疗方法提供了理论依据与研究方向。
Knee osteoarthritis(KOA)is a chronic degenerative joint disease characterized by articular cartilage degeneration,subchondral bone changes,and synovial inflammation,accompanied by joint pain and dysfunction.Nrf2(nuclear factor erythroid 2-related factor 2)is an important antioxidant regulator in cells.It plays a key role in maintaining cell redox balance and protecting tissue function by regulating the expression of downstream antioxidant,anti-inflammatory,and anti-ferroptosis genes.Studies have shown that Nrf2 signaling pathway plays a protective role in the pathogenesis of KOA through a variety of mechanisms.After activation of Nrf2,it can reduce ROS accumulation,alleviate oxidative stress,and protect chondrocytes from oxidative damage by up-regulating the expression of antioxidant enzymes such as HO-1,NQO1,and SOD.Nrf2 attenuates synovial inflammation and cartilage degeneration by inhibiting the activation of NF-κB and NLRP3 inflammasome,reducing the production of pro-inflammatory factors(such as IL-1β,TNF-α).In addition,Nrf2 protects chondrocytes by regulating GPX4 expression,inhibiting lipid peroxidation and ferroptosis,and further delaying KOA.This review systematically summarizes the specific mechanisms of Nrf2 signaling pathway in anti-oxidation,anti-inflammatory,and anti-ferroptosis in KOA,discusses its core role and therapeutic potential in KOA,and emphasizes the effects of these mechanisms alone or in interaction on KOA.It provides a new perspective for understanding the pathogenesis of KOA,and provides a theoretical basis and research direction for the development of multi-target intervention strategies and efficient treatment method for KOA.