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基于 LC-MS 的血清代谢组学分析评估气体爆炸致急性爆震性肺损伤及生物标志物鉴定。

Gas explosion-induced acute blast lung injury assessment and biomarker identification by a LC-MS-based serum metabolomics analysis.

机构信息

Department of Environmental and Occupational Health, School of Public Health, 91593Xinxiang Medical University, Xinxiang, Henan Province, China.

Institute of Toxicology, College of Preventive Medicine, 12525Third Military Medical University, Chongqing, China.

出版信息

Hum Exp Toxicol. 2021 Apr;40(4):608-621. doi: 10.1177/0960327120960761. Epub 2020 Sep 24.

Abstract

The objective of this study was to evaluate the histopathological effect of gas explosion on rats, and to explore the metabolic alterations associated with gas explosion-induced acute blast lung injury (ABLI) in real roadway environment using metabolomics analyses. All rats were exposed to the gas explosion source at different distance points (160 m and 240 m) except the control group. Respiratory function indexes were monitored and lung tissue analysis was performed to correlate histopathological effect to serum metabolomics. Their sera samples were collected to measure the metabolic alterations by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). HE staining in lung showed that the gas explosion caused obvious inflammatory pulmonary injury, which was consistent with respiratory function monitoring results and the serum metabolomics analysis results. The metabolomics identified 9 significantly metabolites different between the control- and ABLI rats. 2-aminoadipic acid, L-methionine, L-alanine, L-lysine, L-threonine, cholic acid and L-histidine were significantly increased in the exposed groups. Citric acid and aconitic acid were significantly decreased after exposure. Pathway analyses identified 8 perturbed metabolic pathways, which provided novel potential mechanisms for the gas explosion-induced ABLI. Therefore, metabolomics analysis identified both known and unknown alterations in circulating biomarkers, adding an integral mechanistic insight into the gas explosion-induced ABLI in real roadway environment.

摘要

本研究旨在评估气体爆炸对大鼠的组织病理学影响,并通过代谢组学分析探讨真实巷道环境中气体爆炸致急性爆震性肺损伤(ABLI)相关的代谢变化。除对照组外,所有大鼠均在不同距离点(160m 和 240m)暴露于气体爆炸源。监测呼吸功能指标,并进行肺组织分析,将组织病理学效应与血清代谢组学相关联。收集其血清样本,通过超高效液相色谱-质谱联用(UPLC-MS)测量代谢变化。肺组织的 HE 染色显示,气体爆炸引起明显的炎性肺损伤,这与呼吸功能监测结果和血清代谢组学分析结果一致。代谢组学鉴定出对照组和 ABLI 大鼠之间有 9 种差异显著的代谢物。暴露组中 2-氨基己二酸、L-蛋氨酸、L-丙氨酸、L-赖氨酸、L-苏氨酸、胆酸和 L-组氨酸显著增加。暴露后柠檬酸和乌头酸显著减少。途径分析鉴定出 8 个失调的代谢途径,为气体爆炸致 ABLI 提供了新的潜在机制。因此,代谢组学分析鉴定了循环生物标志物中既有已知的也有未知的变化,为真实巷道环境中的气体爆炸致 ABLI 提供了整体的机制见解。

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