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胆石症是常见的消化系统疾病，胆道炎症诱发的胆管结构和功能病理性改变与结石形成密切相关，然而胆道迁延不愈所致的慢性炎症和管道结构病理性重塑造成的梗阻、狭窄目前尚无法彻底治愈。先天免疫与胆石形成关系密切，胆道黏膜免疫屏障介导炎症级联反应的放大、维持和调衡，相关深层机制研究可从细胞、分子层面进一步阐明炎症相关胆石症的发病机制，为探索针对性的治疗研发思路提供理论依据和科学导向。先天免疫系统中的中性粒细胞外诱捕网（NETs）和肝巨噬细胞（HMs）是近年国内外研究的最新前沿及热点。本文据此提出胆道黏膜免疫屏障中NETs-HMs介导炎症级联反应建立和维持“肝/胆道免疫-炎症微环境”促成胆道“炎性-上皮间充质转化（EMT）”参与胆石形成这一科学假说并对此进行综述。结果发现，NETs可通过放大局部炎症、诱导胆管上皮细胞炎性EMT及促进细胞外基质异常沉积，参与胆道病理性重塑；HMs通过表型极化转换及分泌炎症介质调控胆道免疫微环境并影响胆汁酸代谢，二者协同构建促胆石形成的微环境。NETs-HMs免疫-炎症轴是胆石症的重要病理基础，靶向该轴有望提供胆石症防治新策略，但两者在胆石形成不同阶段的具体互作网络尚需借助胆石症特异性模型进一步验证。
Abstract：Cholelithiasis is a common digestive system disease. Pathological changes in bile duct structure and function induced by biliary inflammation are closely associated with stone formation. However， the persistent chronic inflammation and the obstruction and stenosis caused by pathological remodeling of the biliary tract remain intractable with current therapies. Innate immunity is closely related to gallstone formation. The biliary mucosal immune barrier mediates the amplification， maintenance， and homeostatic regulation of inflammatory cascade reactions， and further mechanistic studies at the cellular and molecular levels may elucidate the pathogenesis of inflammation-associated cholelithiasis， providing a theoretical basis and scientific guidance for the development of targeted therapeutic strategies. Neutrophil extracellular traps (NETs) and hepatic macrophages (HMs)， the key components of the innate immune system， have emerged as research frontiers in this field. Based on these findings， this review proposes and summarizes the hypothesis that NETs and HMs at the biliary mucosal immune barrier mediate inflammatory cascade reactions to establish and sustain a "hepatic/biliary immune-inflammatory microenvironment，" thereby facilitating biliary "inflammatory epithelial-mesenchymal transition (EMT)" and contributing to gallstone formation. Our review reveals that NETs participate in pathological remodeling of the biliary tract by amplifying local inflammation， inducing inflammatory EMT in biliary epithelial cells， and promoting aberrant extracellular matrix deposition. Meanwhile， HMs regulate the biliary immune microenvironment and influence bile acid metabolism through phenotypic polarization and secretion of inflammatory mediators， synergistically creating a microenvironment conducive to gallstone formation. The NETs-HMs immuno-inflammatory axis represents a critical pathological foundation for cholelithiasis， and targeting this axis may offer novel strategies for its prevention and treatment. However， the specific interaction network between NETs and HMs at different stages of gallstone formation warrants further validation using cholelithiasis-specific models.
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基本信息:
中图分类号:R575.62
引用信息:
[1]赵雨涵,罗澳,蒙健林,等.胆道免疫屏障中中性粒细胞外诱捕网-肝巨噬细胞介导“炎性-上皮间充质转化”促胆石形成[J].安徽医科大学学报().
基金信息:
国家自然科学基金项目（编号：82474507）; 广西自然科学基金项目（编号：2024GXNSFDA010025、2024GXNSFBA010106）; 广西科技计划项目（编号：桂科AB24010130）
2026-09-02
2026-09-02
2026-09-02