Chang Yue, Zhang Wen, Chen Kai, Wang Zhenguo, Xia Shihai, Li Hai
Department of Hepatopancreatobiliary and Splenic Medicine, Characteristic Medical Center of People's Armed Police Force, Tianjin, China.
Tianjin Key Laboratory of Hepatopancreatic Fibrosis and Molecular Diagnosis and Treatment, Tianjin, China.
J Int Med Res. 2019 Nov;47(11):5441-5452. doi: 10.1177/0300060519879323. Epub 2019 Oct 9.
Oxygen deficiency in the plateau environment weakens aerobic metabolism and reduces the energy supply, leading to high-altitude diseases including decreased circulatory function, decreased nutrient and energy supply to tissues and organs, and decreased waste discharge. The involvement of many metabolic pathways is reflected in dramatic changes in levels of endogenous small molecule metabolites. Metabolomics represents a promising technique for mechanistic studies and drug screening, and metabonomics, or quantitative metabolomics, has been increasingly applied to the study of hypoxic diseases and their pathogenesis, as well as to pharmacodynamics at high altitudes. In this article, we review the recent literature on the pathogenesis of altitude hypoxia and the clinical and preclinical metabonomics of drug interventions. Endogenous metabolites and metabolic pathways change significantly under high-altitude hypoxia. Some drug interventions have also been shown to regulate pathway metabolism, and the problems of applying metabonomics to hypoxic diseases at high altitude and the prospects for its future application are summarized.
高原环境中的缺氧会削弱有氧代谢并减少能量供应,导致包括循环功能下降、组织和器官的营养及能量供应减少以及废物排出减少在内的高原病。许多代谢途径的参与体现在内源性小分子代谢物水平的显著变化上。代谢组学是一种用于机制研究和药物筛选的有前途的技术,而代谢物组学,即定量代谢组学,已越来越多地应用于缺氧疾病及其发病机制的研究,以及高原地区的药效学研究。在本文中,我们综述了关于高原缺氧发病机制以及药物干预的临床和临床前代谢物组学的最新文献。在高原缺氧条件下,内源性代谢物和代谢途径会发生显著变化。一些药物干预也已显示出对途径代谢的调节作用,并总结了将代谢物组学应用于高原缺氧疾病的问题及其未来应用前景。