铁转运平衡在“铁-炎”稳态偶联中的研究进展及治疗探讨  

Research progress and therapeutic perspective of iron transport balance based on"iron-inflammation"homeostatic coupling theory

作　　者：杨丽娜 杜欣珂 刘丽[1] 李曼菁 冉庆森[1] 杨庆[1] 孙立东 李玉洁[1] 陈颖[1] 朱晓新[1] 李琦[1] YANG Li-na;DU Xin-ke;LIU Li;LI Man-jing;RAN Qing-sen;YANG Qing;SUN Li-dong;LI Yu-jie;CHEN Ying;ZHU Xiao-xin;LI Qi(Institute of Chinese Materia Medica,China Academy of Chinese Medical Science,Beijing 100700,China)

机构地区：[1]中国中医科学院中药研究所,北京100700

出　　处：《药学学报》2022年第6期1593-1603,共11页Acta Pharmaceutica Sinica

基　　金：中国中医科学院科技创新工程项目(CI2021A05105,CI2021B015);中国中医科学院优秀青年科技人才(创新类)培养专项(ZZ13-YQ-044);国家科技重大专项-重大新药创制项目(2017ZX09101002-002-002);国家自然科学基金青年基金资助项目(81303272)。

摘　　要：铁稳态与炎症稳态具有明确的偶联关系,是机体内环境稳态调节的整合功能单元。通过对细胞内外铁的摄取-释放进行双向调节和跨膜浓度动态管理,“铁转运平衡”成为维系铁稳态的关键机制,更是炎症“促进-消散”平衡的生理基础。病理状态下,以炎症性肠病等疾病为代表,铁转运平衡贯穿炎症“诱发-进展-治疗”的全链条,是疾病炎症微环境复稳的根本前提和有效途径。巨噬细胞是炎症“促-消”稳态的核心调节细胞且密切参与铁转运平衡,是“铁-炎”稳态的重要偶联环节。目前,基于铁转运平衡理论的转化应用明显不足,特别是基于“铁-炎”稳态偶联的药物干预策略无法同时维持二者稳态,显示出较高的复杂性,且尚未得到合理发掘。本综述拟聚焦于巨噬细胞,通过文献挖掘,以表型极化等免疫学过程为窗口,总结、梳理铁转运平衡的理论研究进展;探求、展望基于铁转运平衡进行炎症干预的治疗价值。本综述以铁转运平衡为切入点,将为炎症性肠病、动脉粥样硬化等疾病的药物研发提供必要的知识准备和有益的研究提示。The iron and inflammation homeostasis are closely coupled,forming an integrated functional unit under physiological conditions."Iron transport balance"has become the key mechanism to maintain iron homeostasis through bidirectional regulation of iron uptake and release and dynamic management of transmembrane concentration.It is also the physiological basis for the inflammatory balance between promotion and resolution.Under pathological conditions,represented by inflammatory bowel disease(IBD),disturbed iron transportation was highly involved in almost every step of inflammatory diseases.Therefore,the iron transporting rebalancing provides the mechanistic basis and effective approach for the normalization of inflammatory microenvironment.Macrophage is the key regulator of inflammation homeostasis and determinant for iron transport balance.Unfortunately,the current clinical transformation based on iron transport balance theory has still been insufficient.Sometimes,this strategy even showed high complexity and contradiction,severely restricting its clinical application.By summarizing the theoretical research progress of iron transport balance,especially its relevance to macrophage phenotypic polarization,this review aims to explore the therapeutic value in inflammation intervention by targeting iron transporting balance.This review will provide the necessary knowledge and hints for the research and development of candidate drugs in treating inflammatory diseases.

关 键 词：铁稳态 炎症稳态 巨噬细胞 铁转运平衡 炎症治疗 

分 类 号：R967[医药卫生—药理学]