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脂多糖诱导的肺损伤两种大鼠模型中呼气代谢物混合物的变化。

Alterations in exhaled breath metabolite-mixtures in two rat models of lipopolysaccharide-induced lung injury.

机构信息

Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;

出版信息

J Appl Physiol (1985). 2013 Nov;115(10):1487-95. doi: 10.1152/japplphysiol.00685.2013. Epub 2013 Aug 1.

DOI:10.1152/japplphysiol.00685.2013
PMID:23908314
Abstract

Exhaled breath contains information on systemic and pulmonary metabolism, which may provide a monitoring tool for the development of lung injury. We aimed to determine the effect of intravenous (iv) and intratracheal (IT) lipopolysaccharide (LPS) challenge on the exhaled mixture of volatile metabolites and to assess the similarities between these two models. Male adult Sprague-Dawley rats were anesthetized, tracheotomized, and ventilated for 6 h. Lung injury was induced by iv or IT administration of LPS. Exhaled breath was monitored continuously using an electronic nose (eNose), and hourly using gas chromatography and mass spectrometry (GC-MS). GC-MS analysis identified 34 and 14 potential biological markers for lung injury in the iv and IT LPS models, respectively. These volatile biomarkers could be used to discriminate between LPS-challenged rats and control animals within 1 h after LPS administration. Electronic nose analysis resulted in a good separation 3 h after the LPS challenge. Hexanal, pentadecane and 6,10-dimethyl-5,9-undecadien-2-one concentrations decreased after both iv and IT LPS administration. Nonanoic acid was found in a higher concentration in exhaled breath after LPS inoculation into the trachea but in a lower concentration after iv infusion. LPS-induced lung injury rapidly changes exhaled breath metabolite mixtures in two animal models of lung injury. Changes partly overlap between an iv and an IT LPS challenge. This warrants testing the diagnostic accuracy of exhaled breath analysis for acute respiratory distress syndrome in clinical trials, possibly focusing on biological markers described in this study.

摘要

呼气中含有有关全身和肺部代谢的信息,这可能为肺损伤的发展提供监测工具。我们旨在确定静脉内(iv)和气管内(IT)脂多糖(LPS)挑战对呼气中挥发性代谢物混合物的影响,并评估这两种模型之间的相似性。雄性成年 Sprague-Dawley 大鼠被麻醉、气管切开并通气 6 小时。通过 iv 或 IT 给予 LPS 来诱导肺损伤。使用电子鼻(eNose)连续监测呼气,每小时使用气相色谱和质谱法(GC-MS)监测。GC-MS 分析鉴定出 iv 和 IT LPS 模型中分别有 34 种和 14 种潜在的肺损伤生物标志物。这些挥发性生物标志物可用于在 LPS 给药后 1 小时内区分 LPS 挑战大鼠和对照动物。电子鼻分析在 LPS 挑战后 3 小时得出了良好的分离结果。己醛、十五烷和 6,10-二甲基-5,9-十一碳二烯-2-酮的浓度在 iv 和 IT LPS 给药后均降低。气管内接种 LPS 后,呼气中检测到壬酸的浓度较高,但 iv 输注后浓度较低。LPS 诱导的肺损伤迅速改变两种肺损伤动物模型中的呼气代谢物混合物。iv 和 IT LPS 挑战之间的变化部分重叠。这需要在临床试验中测试呼气分析对急性呼吸窘迫综合征的诊断准确性,可能侧重于本研究中描述的生物标志物。

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