Acute lung injury (ALI) is a clinically common and serious disease, underscoring the urgent need for clarification of its pathogenesis. According to traditional Chinese medicine (TCM) theories on the "lung-spleen-intestine axis" and its correlation with ALI, a high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) metabolomic platform was applied to identify biomarkers from five bio-samples of control and model rats challenged with intratracheally administered lipopolysaccharide (LPS) based on multivariate mathematical statistical analysis. As a result, 19, 24, 24, 15 and 29 altered metabolites were identified in serum, lung, bronchoalveolar lavage fluid (BALF), spleen and feces samples, respectively. Metabolic pathway analysis showed that linoleic acid, sphingolipid, glycerophospholipid and bile acid metabolism pathways were mainly altered by ALI. Additionally, ROC curves were applied to assess the specificity and sensitivity of the biomarkers. ALI characteristic metabolomic spectra were then established to differentiate the control from the model group with a similarity discriminative threshold of 0.7. Additionally, to compare the metabolomic profiles of the five bio-samples and establish metabolic similarities and differences among them, correlation analysis was conducted in order to delineate an objective law of endogenous linkage along the lung-spleen-intestine axis. Therefore, this study provides insights into the mechanisms involved in ALI from a metabolomics perspective, which can be applied in characterization of the mechanism and early disease detection. Graphical abstract.

中文翻译：

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基于HPLC-ESI-QTOF-MS的LPS诱导的急性肺损伤大鼠血清，肺，支气管肺泡灌洗液，脾脏和粪便的代谢组学扰动。

急性肺损伤（ALI）是临床上常见的严重疾病，强调了急需澄清其发病机理。根据“肺脾肠轴”的中医理论及其与ALI的关系，采用高效液相色谱-四极杆飞行时间质谱（HPLC-QTOF-MS）代谢组学平台基于多变量数学统计分析，应用从气管内施用脂多糖（LPS）攻击的对照和模型大鼠的五个生物样品中鉴定生物标志物。结果，分别在血清，肺，支气管肺泡灌洗液（BALF），脾脏和粪便样品中鉴定出19、24、24、15和29种改变的代谢产物。代谢途径分析表明，亚油酸，鞘脂，ALI主要改变了甘油磷脂和胆汁酸的代谢途径。另外，将ROC曲线应用于评估生物标志物的特异性和敏感性。然后建立ALI特征代谢组学光谱图，以区分具有相似判别阈值为0.7的模型组与对照组。此外，为了比较五个生物样品的代谢组学特征并建立它们之间的代谢相似性和差异性，进行了相关分析，以描绘沿肺-脾-肠轴的内源性连锁的客观规律。因此，本研究从代谢组学的角度提供了与ALI相关的机制的见解，可将其应用于机制表征和早期疾病检测。图形概要。