线粒体自噬在低氧性肺动脉高压中的作用及研究进展  

Role and research progress of mitochondrial autophagy in hypoxic pulmonary hypertension

作　　者：黄国阳 徐晨宇 刘璋璐 刘佳原 周珈彤 梁家兴 刘亚莉 樊荣 贾敏 张淑苗 冯娜 顾晓明 李娟 HUANG Guo-yang;XU Chen-yu;LIU Zhang-lu;LIU Jia-yuan;ZHOU Jia-tong;LIANG Jia-xing;LIU Ya-li;FAN Rong;JIA Min;ZHANG Shu-miao;FENG Na;GU Xiao-ming;LI Juan(Department of Physiology and Pathophysiology,School of Basic Medical Science,Air Force Medical University,Xi’an 710032,Shaanxi,China)

机构地区：[1]空军军医大学基础医学院生理与病理生理学教研室,陕西西安710032

出　　处：《心脏杂志》2025年第2期198-203,共6页Chinese Heart Journal

基　　金：陕西省自然科学基础研究计划重点项目(2022JZ-55);国家自然科学基金项目(81470248);陕西省重点研发项目(2023-YBSF-373)。

摘　　要：低氧是多种疾病的病理生理学基础,刺激肺部组织细胞发生一系列变化以适应低氧微环境。线粒体自噬是一种与其他细胞自噬通路相似的选择性细胞自噬途径,在细胞应激中发挥重要作用。近些年研究显示,当细胞受到以低氧刺激为代表的外环境刺激时,可发生一系列应激变化,低氧早期适当的线粒体自噬,从而特异性地清除受损线粒体,减轻细胞损伤,但是随着低氧时间延长,通过激活PINK1/Parkin介导的通路、FUNDC1受体磷酸化以及上调HIF-1α和ROS等机制,促进线粒体自噬,损伤线粒体功能,抑制细胞凋亡,加重细胞增殖。由于肺组织对氧含量最为敏感,长期处于缺氧刺激下会导致肺血管异常收缩和肺小动脉病理性重塑共同作用导致肺循环阻力增加,并最终演变为低氧性肺动脉高压。而线粒体自噬与该过程密切相关,深入研究低氧诱导线粒体自噬的具体机制有望为该疾病的治疗提供新的方向。本文就低氧诱导线粒体自噬的机制及其在低氧性肺动脉高压中所扮角色和已取得的研究进展进行全面综述。Hypoxia is the pathophysiological basis of various diseases,stimulating a series of changes in lung tissue cells to adapt to the hypoxic microenvironment.Mitochondrial autophagy is a selective autophagy pathway similar to other autophagy pathways,which plays an important role in cellular stress.Recently,studies have conveyed that when cells are exposed to environmental stimuli such as low oxygen,a series of stress changes occur.Appropriate mitochondrial autophagy in the early stage of hypoxia can specifically clear damaged mitochondria and alleviate cell damage.However,with prolonged hypoxia,mitochondrial autophagy is promoted,mitochondrial function is damaged,and apoptosis is inhibited through activation of PINK1/Parkin-mediated pathway,FUNDC1 receptor phosphorylation,and up-regulation of HIF-1αand ROS.Increase cell proliferation.Pulmonary tissues are most sensitive to oxygen concentration and in prolonged hypoxic environment,the pathophysiological changes of abnormal contraction of pulmonary vessels and remodeling of pulmonary arterioles would lead to increased pulmonary circulation resistance and hypoxic pulmonary hypertension(HPH).Mitophagy is closely related to its occurrence and development.Further research on the specific mechanism underlying hypoxia-induced mitophagy may provide new directions for the treatment of HPH.This article reviews the mechanisms behind hypoxia-induced mitophagy and its role in hypoxic-induced pulmonary hypertension along with recent research progress.

关 键 词：低氧 线粒体自噬 低氧性肺动脉高压 

分 类 号：R544.1[医药卫生—心血管疾病]