线粒体功能障碍在缺氧性肺动脉高压中的作用  

The Role of Mitochondrial Dysfunction in Hypoxic Pulmonary Hypertension

作　　者：潘舟 胡克[1] PAN Zhou;HU Ke(Department of Respiratory and Critical Care Medicine,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院呼吸与危重症医学科,武汉430060

出　　处：《生物技术进展》2023年第6期882-888,共7页Current Biotechnology

基　　金：国家自然科学基金面上项目(81970082)。

摘　　要：在肺循环中,线粒体除了发挥典型的代谢作用外,还具有调节氧化还原信号、细胞周期、细胞凋亡以及线粒体质量控制等非典型功能。目前,对线粒体在肺循环中的非典型功能及其响应缺氧的作用机制的研究有限,需要对肺动脉高压的生物学标志物和治疗靶点有更多的了解。阐述了缺氧诱导的活性氧(reactive oxygen species,ROS)产生和细胞内钙离子浓度增加,以及缺氧对丙酮酸脱氢酶激酶和丙酮酸激酶M2型表达的影响,总结了线粒体融合和分裂在肺动脉平滑肌细胞增殖、抗凋亡表型等方面的作用,探讨了缺氧对线粒体活性、细胞行为以及线粒体功能障碍对肺动脉高压进展的影响。深入了解调控线粒体氧化信号、代谢和动态平衡的分子机制对研究和治疗肺动脉高压具有重要意义。Mitochondria plays a pivotal role in the pulmonary circulation not only in typical metabolic processes but also in regulating oxidative-reduction signaling,cell cycle progression,cell apoptosis,and mitochondrial quality control,among other noncanonical functions.However,current understanding of these noncanonical mitochondrial functions in the pulmonary circulation and their response to hypoxia is limited.Therefore,there is a need for a deeper understanding of the biological markers and therapeutic targets associated with pulmonary arterial hypertension.This review elucidated the effects of hypoxia on mitochondrial activity and cellular behavior,including the induction of reactive oxygen species(ROS)generation and increased intracellular calcium levels.Furthermore,it highlighted the impact of hypoxia on the expression of pyruvate dehydrogenase kinase and pyruvate kinase M2,as well as the role of mitochondrial fusion and fission in pulmonary artery smooth muscle cell proliferation and resistance to apoptosis.Such investigations contributed to a comprehensive understanding of how hypoxia influences mitochondrial function and how mitochondrial dysfunction affects the progression of PAH.A thorough comprehension of the molecular mechanisms regulating mitochondrial oxidative signaling,metabolism,and dynamic equilibrium holds significant importance in the research and treatment of pulmonary arterial hypertension.

关 键 词：线粒体功能障碍 肺动脉高压 缺氧 活性氧 

分 类 号：Q591[生物学—生物化学] R363[医药卫生—病理学]