摘要
高原低氧性肺动脉高压是机体暴露高原极端环境时发生的复杂的病理生理及临床综合征,也是低氧性肺动脉高压(hypoxic pulmonary hypertension)中的重要类型之一,严重者可引起右心衰竭甚至过早死亡,因此是危害高原居民及急进高原者健康的主要疾病之一。包括高原低氧性肺动脉高压在内的低氧性肺动脉高压确切发病机制仍未完全明确,目前尚缺乏用于干预、治疗低氧性肺动脉高压的有效药物。近年来研究显示,各类型的肺动脉高压患者中普遍存在铁缺乏现象,且铁一方面通过调控低氧诱导因子的活性,影响其靶基因表达;另一方面参与线粒体铁硫簇的生物合成,影响细胞活性氧生成,从而调控低氧性肺动脉高压的发生和进展。更有趣的是,铁和低氧之间存在重要的分子对话机制。因此,铁稳态(iron homeostasis)可能参与和调节低氧性肺动脉高压的发生发展,同时调控铁代谢也有可能成为干预低氧性肺动脉高压的潜在靶点。故本文就铁稳态、铁代谢紊乱与低氧性肺动脉高压,以及干预铁代谢调控低氧性肺动脉高压的可能机制予以简要综述,以期为低氧性肺动脉高压的预防及临床治疗提供新的思路。
Hypoxic pulmonary hypertension at high altitude is a complicated pathophysiological condition and clinical syndrome that occurs after exposure to high altitude.As one of the major types of pulmonary hypertension,high-altitude hypoxic pulmonary hypertension poses a serious threat to the health of residents in plateau areas,with an increased risk of right heart failure and even premature death.However,the exact pathogenesis of hypoxic pulmonary hypertension,including high-altitude hypoxic pulmonary hypertension,has not been fully clarified,effective drugs for treatment still lacking.Recent studies have shown that iron deficiency is prevalent in patients with all types of pulmonary hypertension,and iron affects the expression of hypoxia-inducible factors(HIFs)target genes by regulating the activity of HIFs.Furthermore,iron participates in the biosynthesis of mitochondrial iron-sulfur clusters and regulates the generation of cellular reactive oxygen species(ROS),thereby modulating the occurrence and progression of hypoxic pulmonary hypertension.More intriguingly,there exists an important molecular dialogue between iron and hypoxia.Taken together,we hold the opinion that iron homeostasis may be involved in regulating the occurrence and development of hypoxic pulmonary hypertension,and the regulation of iron metabolism may represent a potential target for the intervention of hypoxic pulmonary hypertension.This article briefly reviewed iron homeostasis,iron metabolism disorders and hypoxic pulmonary hypertension,as well as the possible mechanisms by which the intervention of iron metabolism regulates hypoxic pulmonary hypertension,aiming to provide new ideas for the prevention and treatment of hypoxic pulmonary hypertension.
作者
耿玉梅
格日力
白振忠
GENG Yu-Mei;GE Ri-Li;BAI Zhen-Zhong(Research Center for High Altitude Medicine,Qinghai University,Xining 810001,China;High Altitude Medicine Key Laboratory of the Ministry of Education,Xining 810001,China;Qinghai Provincial Key Laboratory for Application of High Altitude Medicine(Qinghai-Utah Key Laboratory of High Altitude Medicine),Xining 810001,China;Department of Respiratory and Critical Care Medicine,Qinghai Provincial People's Hospital,Xining 810000,China)
出处
《生理科学进展》
CAS
2023年第4期326-333,共8页
Progress in Physiological Sciences
基金
青海省科技厅创新计划“应用与基础”项目(2020-ZJ-721)
2022年青海省昆仑英才创新人才项目(2022年)
中国科学院“西部之光”项目资助课题。
关键词
铁稳态
低氧性肺动脉高压
低氧性肺血管收缩
肺血管重构
iron homeostasis
hypoxic pulmonary hypertension
hypoxic pulmonary vasoconstriction
pulmonary vascular remodeling
