■由于高原地区的经济增长,数百万不同职业的人迁移到高海拔地区工作,高海拔环境失调(HADA)逐渐成为公共卫生问题。HADA会影响暴露于高海拔地区后返回低海拔地区的人。它会引起重大的生理和功能变化,从而对健康产生负面影响,甚至危及生命。然而,关于HADA的详细机制仍然存在不确定性。
■我们建立了HADA患者的群体队列,并评估了代谢物组成的变化。四组的血浆样本,包括停留在平原(P)和高海拔(H)的受试者,以及从高海拔返回平原后几乎没有反应(r3)和轻度至中度反应(R3)的HADA综合征患者,收集并通过液相色谱-质谱代谢组学进行分析。多变量统计分析用于探索代谢物的显著差异和潜在的临床前景。
■尽管目前的HADAS诊断症状评分有显著差异,r3和R3之间的17项常规临床指标没有差异。进一步的多变量分析显示,四组中代谢物的孤立聚类分布,这表明它们的代谢特征存在显著差异。通过K-均值聚类分析,我们鉴定出235种代谢物,这些代谢物表现出与HADA综合征表型一致的丰度变化模式.途径富集分析表明,在高海拔条件下,多不饱和脂肪酸的影响很大。我们比较了R3和r3之间的代谢物,发现107种代谢物具有不同的丰度参与脂质代谢和氧化,表明它们在调节氧化应激稳态中的潜在作用。其中,四种代谢物可能在HADA的发生中起关键作用,包括11-β-羟基雄酮-3-葡糖苷酸,5-甲氧基吲哚乙酸酯,9,10-环氧十八烯酸,和PysoPC(20:5)。
■我们观察了HADA代谢过程的动态变化。四种代谢物的水平,这可能是通过脂质代谢和氧化介导的HADA,预计将探索HADA的前瞻性指标。此外,代谢组学在识别环境危险因素方面比临床检查更有效,当检测到症状差异背后的剧烈代谢紊乱时,为HADAS的分子机制提供新的见解。
UNASSIGNED: High altitude de-acclimatization (HADA) is gradually becoming a public health concern as millions of individuals of different occupations migrate to high-altitude areas for work due to economic growth in plateau areas. HADA affects people who return to lower elevations after exposure to high altitudes. It causes significant physiological and functional changes that can negatively impact health and even endanger life. However, uncertainties persist about the detailed mechanisms underlying HADA.
UNASSIGNED: We established a population cohort of individuals with HADA and assessed variations in metabolite composition. Plasm samples of four groups, including subjects staying at plain (P) and high altitude (H) as well as subjects suffering from HADA syndrome with almost no reaction (r3) and mild-to-moderate reaction (R3) after returning to plain from high altitude, were collected and analyzed by Liquid Chromatography-Mass Spectrometry metabolomic. Multivariate statistical analyses were used to explore significant differences and potential clinical prospect of
metabolites.
UNASSIGNED: Although significantly different on current HADAS diagnostic symptom score, there were no differences in 17 usual clinical indices between r3 and R3. Further multivariate analyses showed isolated clustering distribution of the
metabolites among the four groups, suggesting significant differences in their metabolic characteristics. Through K-means clustering analysis, we identified 235
metabolites that exhibited patterns of abundance change consistent with phenotype of HADA syndrome. Pathway enrichment analysis indicated a high influence of polyunsaturated fatty acids under high-altitude conditions. We compared the
metabolites between R3 and r3 and found 107
metabolites with differential abundance involved in lipid metabolism and oxidation, suggesting their potential role in the regulation of oxidative stress homeostasis. Among them, four metabolites might play a key role in the occurrence of HADA, including 11-beta-hydroxyandrosterone-3-glucuronide, 5-methoxyindoleacetate, 9,10-epoxyoctadecenoic acid, and PysoPC (20:5).
UNASSIGNED: We observed the dynamic variation in the metabolic process of HADA. Levels of four
metabolites, which might be provoking HADA mediated through lipid metabolism and oxidation, were expected to be explore prospective indices for HADA. Additionally, metabolomics was more efficient in identifying environmental risk factors than clinical examination when dramatic metabolic disturbances underlying the difference in symptoms were detected, providing new insights into the molecular mechanisms of HADAS.