运动防治胰岛素抵抗:Keap1/核因子E2相关因子2信号通路的作用与分子机制  

Exercise prevention and treatment of insulin resistance:role and molecular mechanism of Keap1/nuclear factor erythroid2-related factor 2 signaling pathway

作　　者：刘璇[1] 丁雨晴 夏若寒 汪献旺 胡淑娟 Liu Xuan;Ding Yuqing;Xia Ruohan;Wang Xianwang;Hu Shujuan(School of Education and Physical Education,Jingzhou 423000,Hubei Province,China;Department of Medicine,Yangtze University,Jingzhou 423000,Hubei Province,China)

机构地区：[1]长江大学教育与体育学院,湖北省荆州市423000 [2]长江大学医学部,湖北省荆州市423000

出　　处：《中国组织工程研究》2025年第35期7578-7588,共11页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(81974115),项目负责人:夏若寒;山南市本级科技计划项目(SNSBJKJJHXM2024023),项目负责人:汪献旺;湖北省自然科学基金一般项目(JCZRYB202501311),项目负责人:胡淑娟;长江大学大学生创新创业训练计划项目(Yz2023165),项目参与人:胡淑娟。

摘　　要：背景:运动干预在疾病预防和治疗过程中发挥着关键作用,能够有效激活核因子E2相关因子2(nuclear factor erythroid2-related factor 2,Nrf2)信号通路来防治胰岛素抵抗的发生发展,但目前关于靶向Nrf2的运动治疗策略在缓解胰岛素抵抗中的潜在作用机制尚不明晰。目的:以Nrf2、胰岛素抵抗和运动三者的关系为切入点,分析不同运动方式对Nrf2激活的机制及影响,阐明靶向Nrf2的运动治疗策略在缓解胰岛素抵抗过程中的潜在作用机制。方法:以“糖尿病,胰岛素,胰岛素抵抗,核因子E2相关因子2,氧化应激,铁死亡,自噬,炎症反应,运动”为中文检索词;以“Diabetes mellitus,insulin resistance,Keap1/Nrf2,oxidative stress,ferroptosis,autophagy,Inflammatory response,exercise”为英文检索词,在万方数据库、中国知网、Google Scholar和PubMed数据库中搜寻建库以来至2024年10月发表的所有研究文献,根据入选标准最终纳入核心相关文献127篇进行综述。结果与结论:①Keap1/Nrf2信号通路作为重要的内源性抗氧化应激通路,在胰岛素抵抗中扮演着重要角色,其激活可以增强细胞的抗氧化能力,减轻氧化应激和炎症反应,改善胰岛素信号传导,从而对胰岛素抵抗起到保护作用。②多种运动方式(包括有氧运动、抗阻运动和高强度间歇运动等)均可有效激活Nrf2信号,提高抗氧化应激酶活性,增强细胞抗氧化能力,从而在一定程度上缓解了氧化应激损伤。③运动通过激活Nrf2信号通路能够上调血红素加氧酶1、超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽等抗氧化酶活性,增强细胞抗氧化能力;还可以调控铁死亡途径中的关键酶和蛋白质,如谷胱甘肽过氧化物酶4、膜铁转运蛋白1、铁蛋白重链1等,抑制铁死亡途径,促进铁代谢平衡;增强自噬相关基因选择性自噬接头蛋白p62、自噬相关蛋白5/7的表达,提高脂质化形式的微管相BACKGROUND:Exercise interventions play a key role in disease prevention and treatment,which can effectively activate the nuclear factor erythroid2-related factor 2(Nrf2)signaling pathway to prevent the occurrence and development of insulin resistance.However,the potential mechanism of Nrf2-targeting exercise therapy strategies in alleviating insulin resistance remains unclear.OBJECTIVE:Based on the relationship between Nrf2,insulin resistance and exercise,to analyze the mechanism and influence of different exercise modes on the activation of Nrf2,thereby elucidating the potential mechanism of Nrf2-targeting exercise therapy strategies in the process of alleviating insulin resistance.METHODS:“Diabetes mellitus,insulin,insulin resistance,nuclear factor E2 related factor 2,oxidative stress,ferroptosis,autophagy,inflammatory response,exercise”were used as search terms in Chinese and English.WanFang Database,CNKI,Google Scholar and PubMed database were searched for relevant literature from inception to October 2024,and a total of 127 core related articles were obtained according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1)Keap1/Nrf2 signaling pathway,as an important endogenous antioxidant stress pathway,plays an important role in insulin resistance.Activation of Keap1/Nrf2 signaling pathway can enhance the antioxidant capacity of cells,reduce oxidative stress and inflammation,improve insulin signaling,and thus protect insulin resistance.(2)A variety of exercise methods(including aerobic exercise,resistance exercise and high-intensity intermittent exercise)can effectively activate Nrf2 signal,improve the activity of antioxidant kinase and enhance the antioxidant capacity of cells,so as to alleviate oxidative stress damage to a certain extent.(3)By activating Nrf2 signaling pathway,exercise can up-regulate the activity of antioxidant enzymes such as Heme oxygenase 1,superoxide dismutase,catalase,glutathione peroxidase,glutathione,and enhance the antioxidant capacity of cells.In addition,it can

关 键 词：Keap1/Nrf2 胰岛素 胰岛素抵抗 氧化应激 铁代谢 自噬 炎症反应 运动 工程化组织构建 

分 类 号：R459.9[医药卫生—治疗学] R319[医药卫生—临床医学] R87