金属离子在结核病中的作用研究进展  

The research progress on the role of metal ions in tuberculosis

作　　者：陈禹[1,6] 李晓睿 王妙然 张雨颀 刘畅 王照华 石杰 樊丽超 尹智华 谢建平[7] Chen Yu;Li Xiaorui;Wang Miaoran;Zhang Yuqi;Liu Chang;Wang Zhaohua;Shi Jie;Fan Lichao;Yin Zhihua;Xie Jianping(Department of Tuberculosis,The 10th People’s Hospital of Shenyang(Shenyang Chest Hospital),Shenyang,Liaoning,110044,China;Department of Oncology,Liaoning Cancer Hospital,Shenyang 110042,China;Department of Plastic Surgery,The First Affiliated Hospital of China Medical University,Shenyang 110002,China;Department of Science and Education,The 10th People’s Hospital of Shenyang(Shenyang Chest Hospital),Shenyang 110044,China;Department of Thoracic Surgery,The 10th People’s Hospital of Shenyang(Shenyang Chest Hospital),Shenyang 110044,China;School of Public Health,China Medical University,Shenyang 110122,China;College of Life Sciences,Southwest University,Chongqing 400715,China)

机构地区：[1]沈阳市第十人民医院/沈阳市胸科医院结核科,沈阳110044 [2]辽宁省肿瘤医院肿瘤内科,沈阳110042 [3]中国医科大学附属第一医院整形外科,沈阳110002 [4]沈阳市第十人民医院/沈阳市胸科医院科教科,沈阳110044 [5]沈阳市第十人民医院/沈阳市胸科医院胸外科,沈阳110044 [6]中国医科大学公共卫生学院,沈阳110122 [7]西南大学生命科学学院,重庆400715

出　　处：《结核与肺部疾病杂志》2025年第1期102-112,共11页Journal of Tuberculosis and Lung Disease

基　　金：国家自然科学基金(81871626);辽宁省科学技术计划项目(2022-MS-432);沈阳市科技计划项目(24-214-3-107)。

摘　　要：结核分枝杆菌感染引发的结核病仍是全球公共卫生的严峻挑战。过渡金属能够稳定酶活性位点上的底物或反应中间体,广泛参与酶的催化反应过程。细菌与宿主细胞都需精确调节这些金属元素的水平,以满足生理需求并避免潜在的毒性。近年来,越来越多的研究揭示了微生物直接金属中毒的新机制,这些机制被认为是宿主免疫系统的重要组成部分,用于限制病原体的生存。宿主细胞能够通过调节胞内金属离子浓度,如锌、铜、铁等,作为一种先天免疫机制来抑制胞内病原菌的生长。在应对这些挑战的过程中,结核分枝杆菌则具备复杂的金属解毒系统。通过金属泵、螯合剂和抗氧化酶,结核分枝杆菌能够在宿主施加的金属压力下维持金属平衡,逃避宿主的免疫攻击。这些解毒机制对于病原菌的存活和持续感染至关重要。作者对宿主细胞在应对结核分枝杆菌感染过程中的金属离子代谢重编程进行了系统性探讨,深入分析了宿主细胞对不同金属离子的调控机制及其在抗微生物感染中的作用,揭示了金属离子代谢的动态变化和在感染防御中的重要性。理解这些代谢过程不仅有助于揭示结核病的发病机制,为结核病的防控与诊疗提示新的研究方向,也为开发新型抗结核治疗策略提供重要的理论基础。Tuberculosis(TB),caused by Mycobacterium tuberculosis(MTB)infection,remains a major global public health challenge.Transition metals can stabilize substrates or reaction intermediates at the active sites of enzymes and are extensively involved in enzymatic catalytic processes.Both bacteria and host cells must precisely regulate the levels of these metal elements to meet physiological needs while avoiding potential toxicity.In recent years,increasing studies have uncovered new mechanisms of microbial direct metal poisoning,which are considered critical components of the host immune system to restrict pathogen survival.Host cells can regulate intracellular concentrations of metal ions,such as zinc,copper,and iron,as an innate immune mechanism to inhibit the growth of intracellular pathogens.In response to these challenges,MTB possesses complex metal detoxification systems.Through metal pumps,chelator,and antioxidant enzymes,MTB can maintain metal homeostasis under host-imposed metal stress and evade immune attacks.These detoxification mechanisms are essential for the pathogen’s survival and persistent infection.This study systematically explores the reprogramming of metal ion metabolism in host cells during MTB infection,providing an in-depth analysis of host cell regulation of various metal ions and their roles in antimicrobial defense.It reveals the dynamic changes in metal ion metabolism and its significance in infection defense.Understanding these metabolic processes aids in elucidating the pathogenesis of tuberculosis,offers new insights into its prevention and treatment,and provides a theoretical foundation for the development of novel anti-tuberculosis therapeutic strategies.

关 键 词：分枝杆菌 结核 巨噬细胞 金属离子 铜蓝蛋白 

分 类 号：R52[医药卫生—内科学]