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中性粒细胞胞外陷阱各组分对动脉粥样硬化的作用和机制研究进展

陈欣¹, 朱晶静¹, 杨晓帆^1,2, 马钰鹏^1,2, 包怡敏¹, 宁可^2,*

¹上海中医药大学中西医结合学院，上海 201203；²上海中医药大学中医学院，上海 201203

摘要

动脉粥样硬化(atherosclerosis, AS) 作为心血管疾病的主要病理基础，是临床血管病变最常见、最重要的一种类型。深入探究AS的发病机制，对于研发靶向药物具有重要的临床和社会意义。中性粒细胞作为循环系统中数量最多的白细胞类型，在炎症反应中发挥关键作用，与AS 这一血管慢性炎症性疾病密切相关。中性粒细胞胞外陷阱(neutrophil extracellulartraps, NETs)是由中性粒细胞释放的大型网状结构，作为一种关键的免疫防御机制，其在血管内皮细胞损伤导致的血管屏障功能障碍中发挥重要作用。NETs 释放的组分能够损伤血管内皮细胞，后者作为血管壁的第一道防线，其损伤往往是AS发生的起始环节。近年来，NETs 在AS的发生和发展中的作用逐渐受到关注，其复杂多变的成分机制对AS的影响不容忽视。因此，本文以NETs 为核心对象，系统综述了其主要成分(包括核心组蛋白、髓过氧化物酶、组织蛋白酶G、白细胞弹性酶、基质金属蛋白酶、抗菌肽LL-37、alpha-防御素1~3、高迁移率族蛋白B1)与AS 之间的关系。这不仅有助于我们深入理解NETs 在AS中的作用机制，还为未来的研究人员提供新的研究思路，并对NETs 在临床转化方向的应用进行了归纳和总结。

关键词： 动脉粥样硬化; 中性粒细胞胞外陷阱; 核心组蛋白; 髓过氧化物酶; 组织蛋白酶G; 白细胞弹性酶; 基质金属蛋白酶; 抗菌肽LL-37; alpha-防御素1~3; 高迁移率族蛋白B1

Research progress on the impact and mechanism of neutrophil extracellular traps (NETs) components in atherosclerosis

CHEN Xin¹, ZHU Jing-Jing¹, YANG Xiao-Fan^1,2, MA Yu-Peng^1,2, BAO Yi-Min¹, NING Ke^2,*

¹School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China；²School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Abstract

Atherosclerosis (AS) is a prevalent clinical vascular condition and serves as a pivotal pathological foundation for cardiovascular diseases. Understanding the pathogenesis of AS has significant clinical and societal implications, aiding in the development of targeted drugs. Neutrophils, the most abundant leukocytes in circulation, assume a central role during inflammatory responses and closely interact with AS, which is a chronic inflammatory vascular disease. Neutrophil extracellular traps (NETs) are substantial reticular formations discharged by neutrophils that serve as an immune defense mechanism. These structures play a crucial role in inducing dysfunction of the vascular barrier following endothelial cell injury. Components released by NETs pose a threat to the integrity of vascular endothelium, which is essential as it acts as the primary barrier to maintain vascular wall integrity. Endothelial damage constitutes the initial stage in the onset of AS. Recent investigations have explored the intricate involvement of NETs in AS progression. The underlying structures of NETs and their active ingredients, including histone, myeloperoxidase (MPO), cathepsin G, neutrophil elastase (NE), matrix metalloproteinases (MMPs), antimicrobial peptide LL-37, alpha-defensin 1-3, and high mobility group protein B1 have diverse and complex effects on AS through various mechanisms. This review aims to comprehensively examine the interplay between NETs and AS while providing insights into their mechanistic underpinnings of NETs in this condition. By shedding light on this intricate relationship, this exploration paves the way for future investigations into NETs while guiding clinical translation efforts and charting new paths for therapeutic interventions.

Key words: Atherosclerosis; neutrophil extracellular traps; histone; myeloperoxidase; cathepsin G; neutrophil elastase; matrix metalloproteinases; antimicrobial peptide LL-37; alpha-defensin 1-3; high mobility group protein B1

收稿日期：　　录用日期：

通讯作者：宁可　　E-mail:

DOI: 10.13294/j.aps.2025.0013

引用本文：

陈欣, 朱晶静, 杨晓帆, 马钰鹏, 包怡敏, 宁可. 中性粒细胞胞外陷阱各组分对动脉粥样硬化的作用和机制研究进展[J]. 生理学报 2025; 77 (1): 107-119.

CHEN Xin, ZHU Jing-Jing, YANG Xiao-Fan, MA Yu-Peng, BAO Yi-Min, NING Ke. Research progress on the impact and mechanism of neutrophil extracellular traps (NETs) components in atherosclerosis. Acta Physiol Sin 2025; 77 (1): 107-119 (in Chinese with English abstract).