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首页> 外文期刊>High Altitude Medicine & Biology >Effects of Acute Systematic Hypoxia on Human Urinary Metabolites Using LC-MS-Based Metabolomics
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Effects of Acute Systematic Hypoxia on Human Urinary Metabolites Using LC-MS-Based Metabolomics

机译：急性系统缺氧对利用LC-MS基代代谢物的人尿代谢物的影响

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Aims: The metabolic variability and response to acute systematic hypoxia have been characterized by the high resolution of liquid chromatography/time-of-flight/mass spectrometry (LC-TOF/MS) in this study. Specifically, we compared the urinary metabolic profiles of six healthy sedentary men under normoxia (21% O-2) with acute systematic hypoxic conditions of 12% (equivalent to about 4500 m in altitude) and 15% O-2 (equivalent to about 3000 m in altitude) for 2 h in a normobaric hypoxia chamber. Results: A clear separation of dose-dependent responses was visualized by Partial Least Squares Discriminant Analysis (PLS-DA) between normoxic and hypoxic conditions. Over one thousand features were found in this study, about 10% of which showed significant change from hypoxia treatment and 26 metabolites were identified; however, there is great variability in metabolite concentrations among the 6 subjects, which reflects the diversity of human systems. Within the variability, we found that 1-methyladenosine and 5-methylthioadenosine are conspicuously upregulated; on the other hand, 3-inodoleacetic acid and L-glutamic acid were downregulated. Conclusion: The increase in purine metabolic products (uric acid, xanthine, and hypoxathine) results from hypoxia; this increase can be used as a marker for the hypoxic condition. 1-Methyladenosine was also highly upregulated from MH to SH and may be a very sensitive biomarker that reflects cellular hypoxia, due to its potential connection to HIF-1. The increase of free carnitine and acetyl carnitines, on the other hand, signals a change in the pathway of energy, or lipid, metabolism.
机译：目的：通过本研究中的液相色谱/型号/质谱（LC-TOF / MS）的高分辨率，表征了对急性系统缺氧的代谢变异性和反应。具体而言，我们将六种健康久坐性男性的尿代谢谱系与常氧（21％O-2）进行比较，急性系统的缺氧条件为12％（相当于海拔高度约4500米）和15％O-2（相当于约3000在正常缺氧室中的高度）在高度）中。结果：通过常氧和缺氧条件之间的局部最小二乘判别分析（PLS-DA）明确地分离剂量依赖性响应。在本研究中发现了超过一千个特征，其中约10％表现出缺氧治疗和26种代谢物的显着变化;然而，6个受试者中的代谢物浓度有很大的变化，这反映了人类系统的多样性。在可变性内，我们发现1-甲基碳苷和5-甲基噻吩醇显着上调;另一方面，下调了3-季铵酸和L-谷氨酸。结论：缺氧产生嘌呤代谢产物（尿酸，黄嘌呤和低氧阴离子）的增加;这种增加可以用作缺氧条件的标志物。 1-甲基碳糖苷也从MH到SH高度上调，并且可以是非常敏感的生物标志物，其由于其与HIF-1的潜在连接而反射细胞缺氧。另一方面，自由肉碱和乙酰肉碱的增加表示能量或脂质，代谢途径的变化。

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