Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
Department of Medicine, National Jewish Health, Denver, CO, 80206, USA.
Sci Rep. 2017 Jul 11;7(1):5108. doi: 10.1038/s41598-017-05374-1.
This observational study catalogues the overlap in metabolites between matched bronchoalveolar lavage fluid (BALF) and plasma, identifies the degree of congruence between these metabolomes in human and mouse, and determines how molecules may change in response to cigarette smoke (CS) exposure. Matched BALF and plasma was collected from mice (ambient air or CS-exposed) and humans (current or former smokers), and analyzed using mass spectrometry. There were 1155 compounds in common in all 4 sample types; fatty acyls and glycerophospholipids strongly overlapped between groups. In humans and mice, more than half of the metabolites present in BALF were also present in plasma. Mouse BALF and human BALF had a strong positive correlation with 2040 metabolites in common, suggesting that mouse models can be used to interrogate human lung metabolome changes. While power was affected by small sample size in the mouse study, the BALF metabolome appeared to be more affected by CS than plasma. CS-exposed mice showed increased plasma and BALF glycerolipids and glycerophospholipids. This is the first report cataloguing the metabolites present across mouse and human, BALF and plasma. Findings are relevant to translational studies where mouse models are used to examine human disease, and where plasma may be interrogated in lieu of BALF or lung tissue.
这项观察性研究对匹配的支气管肺泡灌洗液(BALF)和血浆中的代谢物重叠进行了编目,确定了人类和小鼠这些代谢组之间的一致性程度,并确定了分子如何响应香烟烟雾(CS)暴露而发生变化。从(暴露于环境空气或 CS 的)小鼠和(当前或曾经吸烟的)人类中收集匹配的 BALF 和血浆,并使用质谱法进行分析。在所有 4 种样本类型中共有 1155 种化合物;脂肪酸酰基和甘油磷脂在各组之间强烈重叠。在人类和小鼠中,BALF 中存在的一半以上的代谢物也存在于血浆中。小鼠 BALF 和人 BALF 之间有很强的正相关性,共有 2040 种代谢物,这表明可以使用小鼠模型来研究人类肺部代谢组的变化。尽管小鼠研究中的小样本量影响了研究的效力,但 BALF 代谢组似乎比血浆更受 CS 影响。暴露于 CS 的小鼠的血浆和 BALF 甘油脂和甘油磷脂增加。这是首次对跨小鼠和人类、BALF 和血浆中存在的代谢物进行编目的报告。这些发现与使用小鼠模型研究人类疾病的转化研究相关,并且可以在没有 BALF 或肺组织的情况下对血浆进行检测。