《生命科学》 2026, 38(1): 182-193
HMGB1在心肺系统疾病中的作用机制及运动防治应用进展
摘 要：
高迁移率族蛋白B1（high mobility group protein B1，HMGB1）作为一种重要的损伤相关分子模式（damage-associated molecular patterns，DAMP），在心肺系统疾病中扮演重要的角色。运动是防治心肺系统疾病的非药物手段，其效果及调控 HMGB1的机制仍需系统梳理。通过检索CNKI、PubMed等数据库近几年相关文献，本文系统解析了心肺系统疾病中HMGB1的表达特征和病理机制，并探讨了运动干预如何通过调节HMGB1的表达和活性来防治心肺疾病。结果发现HMGB1作为关键炎症介质，参与多种心肺系统疾病。运动训练能够降低HMGB1的表达水平，进而抑制氧化应激、炎症和纤维化等，有效减缓心肺系统疾病进展，为心肺系统疾病提供新型干预策略。本综述为临床医生在心肺疾病治疗及预后评估方面提供了重要的科学依据和新的治疗思路。
通讯作者：杨 晗 , Email:yanghan@sdsmu.edu.cn 孙忠广 , Email:sunzhongguang@outlook.com
Abstract:
Cardiopulmonary diseases are a leading cause of mortality worldwide, posing a severe threat to human health. As a key damage-associated molecular pattern (DAMP), high-mobility group box 1 (HMGB1) regulates inflammation, oxidative stress, and fibrosis and is considered a core mediator in the pathogenesis of these conditions. Although exercise is widely recognized as an effective non-pharmacological intervention to improve cardiopulmonary health, the specific mechanisms underlying how exercise modulates HMGB1 to exert protective effects remain fragmented and lack systematic integration. The primary objective of this review is to comprehensively summarize the expression characteristics and pathological roles of HMGB1 in major cardiopulmonary diseases by retrieving recent, relevant literature from databases including CNKI, PubMed, and others, and systematically clarifying how exercise interventions target HMGB1 for the prevention and treatment of these disorders. Through systematic integration, this article aims to provide a solid scientific basis for the clinical management of
cardiopulmonary diseases and open up novel therapeutic strategies. Firstly, this paper describes the structure and dual functions of HMGB1. Structurally, HMGB1 consists of two DNA-binding domains (A-box and B-box) and an acidic C-terminal tail. Functionally, it exhibits duality depending on the cellular microenvironment: under physiological conditions, HMGB1 is localized in the nucleus and participates in DNA replication, transcription, and repair; when cells are subjected to damage or infection, it is released extracellularly to act as a pro-inflammatory mediator. Secondly, the pathogenic mechanisms of HMGB1 in specific cardiopulmonary diseases are summarized. In cardiovascular diseases, HMGB1 can activate T cells to exacerbate hypertension; accelerate the progression of myocardial infarction through apoptosis mediated by the TLR4/NF-κB pathway; and drive the development of atherosclerosis via the ox-LDL-HMGB1-endothelial injury vicious cycle. In pulmonary diseases, HMGB1 participates in airway inflammation in asthma through pathways such as HMGB1/TLR4/NF-κBand HMGB1/RAGE; promotes pro-inflammatory responses to aggravate ventilator-induced or sepsis-induced lung injury; and regulates macrophage polarization and vascular remodeling, which is associated with poor prognosis in chronic obstructive pulmonary disease (COPD) and pulmonary arterial hypertension (PAH). The core section of this article focuses on exercise interventions. Moderate-intensity aerobic exercise can downregulate HMGB1 expression, inhibit downstream inflammatory and fibrotic pathways, and improve the prognosis of diseases, such as hypertension, myocardial infarction, and asthma. For COPD patients, low-intensity exercise combined with pursed-lip and diaphragmatic breathing can suppress HMGB1 while avoiding airway injury. High-intensity exercise may transiently increase HMGB1 levels, whereas long-term moderate intensity training achieves sustained inhibition of HMGB1. In addition, this review emphasizes that the regulation of HMGB1 by exercise is significantly influenced by duration, intensity, and type, underscoring the need for personalized exercise prescriptions. Based on this review, HMGB1 can serve as a core therapeutic target for cardiopulmonary diseases. In clinical practice, combining exercise interventions to downregulate HMGB1 expression and inhibit its downstream inflammatory pathways may delay disease progression, whereas inappropriate exercise should be avoided depending on the disease type. Future research should focus on investigating the mechanisms by which exercise modulates HMGB1 to ameliorate pulmonary arterial hypertension, conducting large-scale prospective trials to verify the clinical value of HMGB1 as a diagnostic and prognostic biomarker for diseases, and optimizing personalized exercise prescriptions by considering individual differences such as age and gender, thereby promoting the translation of theoretical findings into clinical applications.
Communication Author：YANG Han , Email:yanghan@sdsmu.edu.cn SUN Zhong-Guang , Email:sunzhongguang@outlook.com
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