[1]简红利,周远发,陀子能.HMGB1/RAGE信号通路在慢性阻塞性肺疾病气道炎症发生和发展中的作用研究进展[J].陕西医学杂志,2026,(8):1144-1147，封三.[doi:DOI:10.3969/j.issn.1000-7377.2026.08.022]
　JIAN Hongli,ZHOU Yuanfa,TUO Zineng.Research progress on the role of HMGB1/RAGE signaling pathway in the occurrence and development of airway inflammation in chronic obstructive pulmonary disease[J].,2026,(8):1144-1147，封三.[doi:DOI:10.3969/j.issn.1000-7377.2026.08.022]
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HMGB1/RAGE信号通路在慢性阻塞性肺疾病气道炎症发生和发展中的作用研究进展

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年8期
页码:
1144-1147，封三
栏目:
综述
出版日期:
2026-08-05

文章信息/Info

Title:
Research progress on the role of HMGB1/RAGE signaling pathway in the occurrence and development of airway inflammation in chronic obstructive pulmonary disease
作者:
简红利1; 周远发2; 陀子能1; 2
（1.广东医科大学第一临床医学院，广东 湛江 524023；2.高州市人民医院呼吸与危重症医学科，广东 高州 525200）
Author(s):
JIAN Hongli1; ZHOU Yuanfa2; TUO Zineng1; 2
（1.The First School of Clinical Medicine of Guangdong Medical University,Zhanjiang 524023,China;2.Department of Respiratory and Critical Care Medicine,Gaozhou People’s Hospital,Gaozhou 525200,China)
关键词:
慢性阻塞性肺疾病; 高迁移率族蛋白B1; 晚期糖基化终末产物受体; 气道炎症; 氧化应激; 气道重塑
Keywords:
Chronic obstructive pulmonary disease; High mobility group protein B1; Receptor for advanced glycation end products; Airway inflammation; Oxidative stress; Airway remodeling
分类号:
R 563
DOI:
DOI:10.3969/j.issn.1000-7377.2026.08.022
文献标志码:
A
摘要:
慢性阻塞性肺疾病（COPD）是一种以持续性气流受限、气道慢性炎症为核心特征的慢性呼吸系统疾病，其发病率与致死率长期居高不下，发病机制复杂且尚未完全阐明。高迁移率族蛋白B1（HMGB1）是经典的损伤相关分子模式蛋白，其与晚期糖基化终末产物受体（RAGE）结合形成的HMGB1/RAGE信号轴，是COPD气道炎症发生和发展的核心调控通路。现对HMGB1/RAGE信号通路在COPD气道炎症级联反应、氧化应激失衡、蛋白酶-抗蛋白酶系统紊乱及气道重塑中的核心作用机制以及靶向该通路的干预策略进行综述，旨在为COPD的早期诊断和靶向治疗提供理论依据。
Abstract:
Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with persistent airflow limitation and chronic airway inflammation as its core features.Its incidence and mortality rates have remained high for a long time,and its pathogenesis is complex and has not been fully elucidated.High mobility group protein B1 (HMGB1) is a classic damage-associated molecular pattern protein.The HMGB1/RAGE signaling axis formed by its binding to the receptor for advanced glycation end products (RAGE) is a core regulatory pathway for the occurrence and development of airway inflammation in COPD.This article reviews the core mechanism of the HMGB1/RAGE signaling pathway in the airway inflammatory cascade,oxidative stress imbalance,protease-antiprotease system disorder and airway remodeling of COPD,as well as intervention strategies targeting this pathway,aiming to provide a theoretical basis for the early diagnosis and targeted therapy of COPD.

参考文献/References:

[1]GAO D,ZHANG W,ZHANG Y,et al.Reallocation time of accelerometer-measured movement behaviours,genetic susceptibility,and incident chronic obstructive pulmonary disease[J].Pulmonology,2026,32(1):2649099.
[2]ADHIKARI P,RANA R,PUNJA R,et al.Prevalence and impact of hyponatremia in chronic obstructive pulmonary disease.A systematic review and meta-analysis[J].Libyan J Med,2026,21(1):2642904.
[3]杨丽娜,张文爱,马雪梅,等.慢性阻塞性肺疾病急性加重期患者多重耐药菌感染病原学分布及与Th1/Th2细胞因子含量的关系[J].临床误诊误治,2026,39(1):30-37.
[4]逯朝凤,李茂,刘娟.误诊为房间隔缺损的慢性阻塞性肺疾病原因分析及超声心动图特征[J].临床误诊误治,2026,39(2):1-7.
[5]丁静,周进,张艳红,等.补肺保元膏联合无烟灸治疗老年慢性阻塞性肺疾病稳定期肺肾气虚证患者的临床疗效观察[J].实用心脑肺血管病杂志,2023,31(1):95-101.
[6]POUWELS S D,HESSE L,WU X,et al.LL-37 and HMGB1 induce alveolar damage and reduce lung tissue regeneration via RAGE[J].Am J Physiol Lung Cell Mol Physiol,2021,321(4):L641-L652.
[7]FURCI F,MURDACA G,PELAIA C,et al.TSLP and HMGB1:Inflammatory targets and potential biomarkers for precision medicine in asthma and COPD[J].Biomedicines,2023,11(2):437.
[8]张阳,郑庆凯,陈苗,等.重症肺炎患者外泌体HMGB1/RAGE/NF-κB基因表达及其与病情进展的关系[J].中华医院感染学杂志,2023,33(6):816-820.
[9]MU Q,WANG Q,YANG Y,et al.HMGB1 promotes M1 polarization of macrophages and induces COPD inflammation[J].Cell Biol Int,2025,49(1):79-91.
[10]宋承鑫,郑丹丹,马起虹,等.高迁移率族蛋白1在急性肺损伤中作用机制研究进展[J].中国急救医学,2025,45(9):809-814.
[11]CURTIS K L,CHANG A,VAN SLOOTEN R,et al.Availability of receptors for advanced glycation end-products (RAGE) influences differential transcriptome expression in lungs from mice exposed to chronic secondhand smoke (SHS)[J].Int J Mol Sci,2024,25(9):4940.
[12]WANG F,ZHAO Y,XING J,et al.Avicularin as a promising therapeutic agent for gestational diabetes mellitus:Modulation of inflammatory,oxidative stress,and apoptotic pathways[J].Dokl Biochem Biophys,2025,521(1):206-220.
[13]FRICKE-GALINDO I,GARCA-CARMONA S,ALANIS-PONCE J,et al.sRAGE levels are decreased in plasma and sputum of COPD secondary to biomass-burning smoke and tobacco smoking:Differences according to the rs3134940 AGER variant[J].Heliyon,2024,10(7):28675.
[14]全紫瑶,陈菁,武小杰,等.慢性阻塞性肺疾病患者血清S100A8/A9和sRAGE水平变化及临床意义[J].中华检验医学杂志,2020,43(2):165-170.
[15]牛业文,马莲美.HMGB-1/NF-κB信号通路与呼吸系统疾病关系的研究进展[J].吉林医学,2025,46(12):3118-3121.
[16]方莉,张璐,石梦瑶,等.基于HMGB1/TLR4/NF-κB信号通路探讨芪白平肺胶囊对COPD大鼠气道炎症的影响[J].中成药,2025,47(1):244-249.
[17]伍新诚,刘雨,柏正平.复方葶苈子汤通过调控HMGB1介导的细胞焦亡及免疫失衡治疗COPD相关性肺动脉高压[J].中国中药杂志,2023,48(11):3055-3065.
[18]杨芳英,黄健,刘艳丰.黄连素介导NF-κB/LCN2信号通路改善COPD诱导的Th17/Treg细胞失衡[J].免疫学杂志,2024,40(7):561-567.
[19]赵一龙,张兆剑,王国威,等.九味健步饮介导HMGB1/RAGE/PI3K/Akt信号通路对膝骨关节炎大鼠氧化应激和炎性损伤的影响[J].医学研究杂志,2025,54(8):48-55.
[20]WAHBA A S,WAHBA N S,SAYED G A,et al.Combined neuroprotective potential of vitamin E and levodopa/carbidopa in a rat model of rotenone-induced Parkinson’s disease:Role of AMPK/SIRT1/PGC-1α and HMGB1/RAGE axes[J].J Pharm Pharmacol,2025,77(10):1386-1401.
[21]SANDERS K A,DELKER D A,HUECKSTEADT T,et al.RAGE is a critical mediator of pulmonary oxidative stress,alveolar macrophage activation and emphysema in response to cigarette smoke [J].Sci Rep,2019,9(1):231.
[22]FREY D L,HELM B,GUERRA M,et al.SputOMICs identifies common and distinct markers in cystic fibrosis and chronic obstructive pulmonary disease[J].Sci Rep,2025,15(1):44418.
[23]马红红,耑冰,杨朝.HMGB1/RAGE通路在COPD和肺癌发病中共性机制的研究进展[J].医学综述,2023,29(18):3597-3601.
[24]CHUNG F T,HUANG H Y,LO C Y,et al.Increased ratio of matrix metalloproteinase-9 (MMP-9)/tissue inhibitor metalloproteinase-1 from alveolar macrophages in chronic asthma with a fast decline in FEV1 at 5-year follow-up[J].J Clin Med,2019,8(9):1451.
[25]BHAT S M,MASSEY N,KARRIKER L A,et al.Ethyl pyruvate reduces organic dust-induced airway inflammation by targeting HMGB1-RAGE signaling[J].Respir Res,2019,20(1):27.
[26]方莉,张璐,杨程,等.芪白平肺胶囊调控HMGB1/TLR2/NF-κB信号通路干预COPD气道重塑的作用机制[J].中药药理与临床,2025,41(7):26-31.
[27]热依拉·牙合甫,买热木古·阿不都热依木,王琴,等.下调HMGB1表达通过抑制炎性反应与上皮间质转化改善慢性阻塞性肺疾病小鼠疾病进展[J].细胞与分子免疫学杂志,2022,38(8):685-691.
[28]王心恒.基于ROS/HMGB1/Beclin-1介导的细胞自噬研究平喘宁方缓解支气管哮喘气道炎症的作用机制[D].合肥:安徽中医药大学,2020.
[29]廖泳,吴晓飞,王芳莉,等.百草枯中毒急性肺损伤的作用机制及丙酮酸乙酯干预研究[J].安徽医药,2017,21(4):630-634.
[30]谢娜,吕兴华,于澄,等.丙酮酸乙酯对脓毒症急性肺损伤大鼠的作用及其机制研究[J].中国现代医学杂志,2020,30(6):14-17.
[31]尚立芝,李耀洋,季书,等.二陈汤加味通过HMGB1/RAGE/NF-κB信号通路对COPD大鼠细支气管炎症的影响[J].中国实验方剂学杂志,2023,29(6):44-54.
[32]徐慧.噻托溴铵在香烟烟雾诱导的COPD小鼠中的作用及机制研究[D].广州:华南理工大学,2023.
[33]刘礼荣,符诒慧,周黎明,等.抑制HMGB1对支气管哮喘小鼠气道炎症的影响及机制[J].中华医院感染学杂志,2022,32(11):1632-1637.
[34]CHANDANNA SERI V,KALEEM ULLAH M,SIDDAIAH J B,et al.Reduced serum sRAGE levels identify COPD and reflect disease severity:Findings from a cross-sectional study in India[J].Diagnostics (Basel),2025,15(22):2910.
[35]丁健,陶慧,程刚,等.韩明向分期分证治疗慢性阻塞性肺疾病经验[J].中医杂志,2025,66(8):780-785.
[36]GE B,LIAO X,LAI F,et al.Effects of traditional chinese exercise on mental health and physical function with chronic obstructive pulmonary disease:A systematic review and meta-analysis[J].Physiother Res Int,2026,31(2):70193.
[37]陈萌,白雨辰,汪铮.牡荆素对肺泡上皮细胞HMGB1/RAGE通路及炎症损伤的影响[J].热带医学杂志,2021,21(2):156-159,165.
[38]关君艳,沈文婷,刘晓辉,等.山柰酚调控HMGB1/RAGE通路对哮喘小鼠气道炎症的影响[J].贵州医科大学学报,2025,50(6):831-839.
[39]李慧,李璐璐.芒柄花素对脓毒症大鼠急性肺损伤和免疫功能的影响及其机制[J].解剖学研究,2024,46(3):236-241.
[40]王燕,齐文杰,曾亚薇,等.厚朴酚治疗重症急性胰腺炎大鼠模型并发急性肺损伤的作用机制[J].临床肝胆病杂志,2020,36(12):2782-2787.

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备注/Memo

备注/Memo:
国家自然科学基金资助项目（81871883）
更新日期/Last Update: 2026-08-13