从分子机制到治疗策略：中性粒细胞胞外陷阱在急性肺损伤中的作用

doi:10.16431/j.cnki.1671-7236.2025.09.041

摘要/Abstract

摘要： 中性粒细胞胞外陷阱(neutrophil extracellular traps，NETs)是中性粒细胞在应对炎症反应时释放的复杂结构，由DNA、组蛋白和多种抗菌蛋白质交织而形成的一种网状物，在防御病原体入侵的同时，过度积累也可能导致组织损伤和炎症加剧。近年来，NETs在急性肺损伤(acute lung injury，ALI)中的病理作用受到了广泛关注。笔者综述了NETs在ALI中形成的分子机制、病理影响及作为治疗靶点的潜力。首先概述了NETs的组成、结构和形成过程，揭示了NETs中的DNA骨架及组蛋白和抗菌蛋白的结合模式，以及中性粒细胞激活后肽酰基精氨酸脱亚氨酶4(peptidylarginine deiminase 4,PAD4)使组蛋白瓜氨酸化，降低其与DNA的结合力最终导致NETs的形成和排出。其次分析了NETs形成的信号通路和调控机制，包括活性氧(reactive oxygen species，ROS)的产生、染色质解聚及自噬的作用，这些过程共同促进了NETs的形成。接着讨论了NETs在ALI中的病理作用，包括其与多种刺激因素的关系、对肺泡损伤和炎症反应的影响，以及NETs成分对肺泡上皮和内皮细胞的破坏作用。此外，还评估了NETs作为ALI治疗靶点的潜力，包括NETs成分作为诊断生物标志物的可能性及在ALI中NETs相关生物标志物的检测方法。最后，对NETs在ALI治疗中的策略进行了探讨，包括药物干预和免疫调节方法，以及其在调节NETs的形成和降解中的作用，期望为ALI的治疗提供理论基础，并为未来的研究提供新的方向。

关键词: 中性粒细胞胞外陷阱; 急性肺损伤; 分子机制; 治疗策略

Abstract: Neutrophil extracellular traps (NETs) are complex structures released by neutrophils in response to inflammatory reactions,composed of DNA,histones,and various antimicrobial proteins,forming a web-like structure.While they defend against pathogen invasion,excessive accumulation can also lead to tissue damage and exacerbation of inflammation.In recent years,the pathological role of NETs in acute lung injury (ALI) has attracted widespread attention.The authors summarize the molecular mechanisms of NET formation in ALI,their pathological effects,and their potential as therapeutic targets.This article outlines the composition,structure,and formation process of NETs,revealing the DNA backbone in NETs and the binding pattern of histones and antimicrobial proteins,as well as the activation of peptidylarginine deiminase 4 (PAD4) in neutrophils that leads to the citrullination of histones,reducing their binding affinity to DNA and ultimately resulting in the formation and extrusion of NETs.This review analyzes the signaling pathways and regulatory mechanisms of NET formation,including the production of reactive oxygen species (ROS),chromatin decondensation,and the role of autophagy,which collectively promote the formation of NETs.Subsequently,this article discusses the pathological role of NETs in ALI,including their relationship with various stimuli,their impact on alveolar injury and inflammatory responses,and the destructive effects of NET components on alveolar epithelial and endothelial cells.Additionally,this review assesses the potential of NETs as therapeutic targets for ALI,including the possibility of NET components as diagnostic biomarkers and the detection methods for NET-related biomarkers in ALI.Lastly,the strategies of NETs in the treatment of ALI are explored,including pharmacological interventions and immunomodulatory methods,and their roles in regulating the formation and degradation of NETs,so as to provide a theoretical basis for the treatment of ALI and offer new directions for future research.

Key words: neutrophil extracellular traps; acute lung injury; molecular mechanisms; therapeutic strategies

中图分类号:

S852.4^＋2

王天鸽, 高爽, 林树梅, 赵冬冬. 从分子机制到治疗策略：中性粒细胞胞外陷阱在急性肺损伤中的作用[J]. 中国畜牧兽医, 2025, 52(9): 4464-4470.

WANG Tiange, GAO Shuang, LIN Shumei, ZHAO Dongdong. From Molecular Mechanisms to Therapeutic Strategies: The Role of Neutrophil Extracellular Traps in Acute Lung Injury[J]. China Animal Husbandry & Veterinary Medicine, 2025, 52(9): 4464-4470.

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