Pathogenesis of ventilator-induced lung injury: metabolomics analysis of the lung and plasma
Pathogenesis of ventilator-induced lung injury: metabolomics analysis of the lung and plasma
复制标题
呼吸机所致肺损伤的发病机制：肺和血浆的代谢组学分析
DOI：
10.1007/s11306-022-01914-7
复制
发表时间：
2022
期刊：
影响因子：
3.6
通讯作者：
Xinru Liu
中科院分区：
文献类型：
--
作者：
Yanfei Mao;Zhixin Ma;Chufan Xu;Zhou lv;Wenwen Dong;Xinru Liu
目前，机械通气（MV）旨在休息呼吸肌，同时提供足够的气体交换，它已成为全麻期间以及有或无呼吸衰竭的危重患者的基本生命支持的一部分。然而，MV本身有可能导致或加重肺损伤，这也被称为呼吸机诱导的肺损伤（VILI）。方法健康小鼠随机分为对照组、高容量潮气量组（HV）（30 ml/kg）和低容量潮气量组（LV）（6 ml/kg）。通气4 h后处死小鼠，收集肺组织和血浆。处理肺和血浆用于代谢组学分析。结果与正常组和LV组相比，HV组肺泡间隔增厚，肺组织出现中度炎性损害;代谢组学分析结果显示，MV改变了肺组织的代谢，表现为γ-氨基丁酸（GABA）系统和尿素循环的失调（血浆和肺胍基琥珀酸、胍基琥珀酸、琥珀酸半醛和肺GABA调节异常），柠檬酸循环（CAC）紊乱（血浆谷氨酰胺和肺磷酸烯醇丙酮酸增加）和氧化还原失衡（血浆和/或肺中抗坏血酸、鹅去氧胆酸、尿酸、油酸、十八碳四烯酸、棕榈油酸和二十二碳六烯酸的失调）。此外，LV组和HV组的肺和血浆代谢物组也存在显着差异。结论与GABA系统、尿素循环、柠檬酸循环和氧化还原平衡相关的一些肺和血浆代谢物发生了显着改变，它们可用于VILI的评估并作为治疗VILI的靶点。
IntroductionNowadays,the mechanical ventilation (MV) aims to rest the respiratory muscles while providing adequate gas exchange, and it has been a part of basic life support during general anesthesia as well as in critically ill patients with and without respiratory failure. However, MV itself has the potential to cause or worsen lung injury, which is also known as ventilator-induced lung injury (VILI). Thus, the early diagnosis of VILI is of great importance for the prevention and treatment of VILI.ObjectiveThis study aimed to investigate the metabolomes in the lung and plasma of mice receiving mechanical ventilation (MV).MethodsHealthy mice were randomly assigned into control group; (2) high volume tidal (HV) group (30 ml/kg); (3) low volume tidal (LV) group (6 ml/kg). After ventilation for 4 h, mice were sacrificed and the lung tissue and plasma were collected. The lung and plasma were processed for the metabolomics analysis. We also performed histopathological examination on the lung tissue.ResultsWe detected moderate inflammatory damage with alveolar septal thickening in the HV group compared with the normal and LV groups.The metabolomics analysis results showed MV altered the metabolism which was characterized by the dysregulation of γ-amino butyric acid (GABA) system and urea cycle (desregulations in plasma and lung guanidinosuccinic acid, argininosuccinic acid, succinic acid semialdehyde and lung GABA ), Disturbance of citric acid cycle (CAC) (increased plasma glutamine and lung phosphoenol pyruvate) and redox imbalance (desregulations in plasma and/or lung ascorbic acid, chenodeoxycholic acid, uric acid, oleic acid, stearidonic acid, palmitoleic acid and docosahexaenoic acid). Moreover, the lung and plasma metabolomes were also significantly different between LV and HV groups.ConclusionsSome lung and plasma metabolites related to the GABA system and urea cycle, citric acid cycle and redox balance were significantly altered, and they may be employed for the evaluation of VILI and serve as targets in the treatment of VILI.