NIHR Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton SO16 6YD, UK.
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK.
Int J Mol Sci. 2024 Sep 29;25(19):10480. doi: 10.3390/ijms251910480.
Acute lung Injury leads to alterations in surfactant lipid composition and metabolism. Although several mechanisms contribute to dysregulated surfactant metabolism, studies investigating in vivo surfactant metabolism are limited. The aim of this study is to characterise surfactant phospholipid composition and flux utilising a stable isotope labelling technique in mechanically ventilated paediatric patients. Paediatric patients (<16 years of age) received 3.6 mg/kg intravenous -D-choline chloride followed by the endotracheal instillation of 100 mg/kg of exogenous surfactant after 24 h. Bronchioalveolar fluid samples were taken at baseline and 12, 24, 36, 48, 72 and 96 h after -D-choline infusion. Nine participants (median age of 48 days) were recruited. The primary phosphatidylcholine (PC) composition consisted of PC16:0/16:0 or DPPC (32.0 ± 4.5%). Surfactant supplementation resulted in a 30% increase in DPPC. -D PC enrichment was detected after 12 h and differed significantly between patients, suggesting variability in surfactant synthesis/secretion by the CDP-choline pathway. Peak enrichment was achieved (0.94 ± 0.15% of total PC) at 24 h after -D-choline infusion. There was a trend towards reduced enrichment with the duration of mechanical ventilation prior to study recruitment; however, this was not statistically significant ( = 0.19). In this study, we demonstrated the fractional molecular composition and turnover of surfactant phospholipids, which was highly variable between patients.
急性肺损伤导致表面活性剂脂质组成和代谢发生改变。尽管有几种机制导致表面活性剂代谢失调，但研究表明，研究体内表面活性剂代谢的研究是有限的。本研究旨在利用稳定同位素标记技术，对机械通气的儿科患者的表面活性剂磷脂组成和通量进行特征描述。儿科患者（<16 岁）接受 3.6mg/kg 的静脉内-D-胆碱氯化物，24 小时后经气管内滴注 100mg/kg 的外源性表面活性剂。在-D-胆碱输注后 12、24、36、48、72 和 96 小时时采集支气管肺泡液样本。招募了 9 名参与者（中位年龄为 48 天）。主要的磷脂酰胆碱（PC）组成由 PC16:0/16:0 或 DPPC（32.0±4.5%）组成。表面活性剂补充导致 DPPC 增加 30%。在 12 小时后检测到-D-PC 富集，并且患者之间存在显著差异，这表明 CDP-胆碱途径的表面活性剂合成/分泌存在差异。在-D-胆碱输注后 24 小时达到峰值富集（总 PC 的 0.94±0.15%）。在研究招募之前，机械通气的持续时间与富集呈下降趋势；然而，这没有统计学意义（=0.19）。在这项研究中，我们展示了表面活性剂磷脂的分数分子组成和周转率，患者之间存在很大的差异。
