摘要
肾脏纤维化是慢性肾脏病进展为终末期肾衰竭的核心途径,靶向肾脏纤维化的治疗策略为临床延缓急性肾损伤向慢性肾脏病转化提供了重要路径。巨噬细胞因来源与表型高度异质,在多种急性炎症、组织修复及纤维化各阶段进展中发挥了重要作用,在肾脏纤维化的治疗中具有巨大的应用前景。本文综述了肾脏巨噬细胞在急性肾损伤向慢性肾脏病转化过程中的关键作用,重点阐述其时相性表型重编程特征,以及由损伤小管-巨噬细胞-成纤维细胞构成的纤维化微环境交互网络。在此基础上,系统梳理了靶向巨噬细胞的4类核心干预策略:调控上游信号通路、诱导巨噬细胞表型重编程、阻断促纤维化因子及其下游通路、选择性耗竭或工程化改造促纤维化巨噬细胞亚群,旨在为未来探索巨噬细胞靶向治疗的干预时机、精度与疗效提供新思路。
Renal fibrosis represents the core pathway through which chronic kidney disease progresses to end-stage renal failure.Therapeutic strategies targeting renal fibrosis provide an important approach for clinically mitigating the transition from acute kidney injury to chronic kidney disease.Macrophages,owing to their high heterogeneity in origin and phenotype,play a significant role in various stages of acute inflammation,tissue repair,and fibrosis,thereby holding substantial promise for the treatment of renal fibrosis.This review summarizes the pivotal role of renal macrophages in the transition from acute kidney injury to chronic kidney disease,with a focus on their temporal phenotypic reprogramming characteristics and the fibrotic microenvironment interaction network constituted by injured tubules,macrophages,and fibroblasts.On this basis,we systematically outline four core categories of macrophage-targeted intervention strategies:modulation of upstream signaling pathways,induction of macrophage phenotypic reprogramming,blockade of profibrotic factors and their downstream pathways,and selective depletion or engineered modification of profibrotic macrophage subsets.This review aims to provide new insights for future exploration of the timing,precision,and efficacy of macrophage-targeted therapies.
作者
祝家豪
徐鲁斌
陈丽萌
ZHU Jiahao;XU Lubin;CHEN Limeng(Department of Nephrology,Beijing Key Laboratory of Molecular Pathology Diagnosis and Translational Research on Rare and Complex Urinary System Diseases,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China)
出处
《协和医学杂志》
北大核心
2026年第2期324-333,共10页
Medical Journal of Peking Union Medical College Hospital
基金
中央高水平医院临床科研专项(2025-PUMCH-C-023)
北京市自然科学基金(7252112)
北京高层次创新创业人才支持计划“医疗卫生平台”领军人才项目(G202511003)
中国医学科学院医学与健康科技创新工程(CIFMS 2024-I2M-C&T-C-003)
国家自然科学基金(82570826)。
关键词
巨噬细胞
急性肾损伤
慢性肾脏病
肾脏纤维化
macrophage
acute kidney injury
chronic kidney disease
renal fibrosis
