Department of Biochemistry and Molecular Biology and Research Institute "Hospital 12 de Octubre (imas12)", Complutense University, Madrid, Spain.
Division of Pediatrics and Neonatal Critical Care, A. Béclère Medical Center, Paris Saclay University Hospitals, APHP, Paris, France.
Am J Respir Cell Mol Biol. 2020 Sep;63(3):327-337. doi: 10.1165/rcmb.2019-0413OC.
No data are available regarding the effect of meconium on human surfactant in the early stages of severe meconium aspiration syndrome (MAS). In the present study, we sought to characterize the changes in surfactant composition, function, and structure during the early phase of meconium injury. We designed a translational prospective cohort study of nonbronchoscopic BAL of neonates with severe MAS ( = 14) or no lung disease ( = 18). Surfactant lipids were analyzed by liquid chromatography-high-resolution mass spectrometry. Secretory phospholipase A subtypes IB, V, and X and SP-A (surfactant protein A) were assayed by ELISA. SP-B and SP-C were analyzed by Western blotting under both nonreducing and reducing conditions. Surfactant function was assessed by adsorption test and captive bubble surfactometry, and lung aeration was evaluated by semiquantitative lung ultrasound. Surfactant nanostructure was studied using cryo-EM and atomic force microscopy. Several changes in phospholipid subclasses were detected during MAS. Lysophosphatidylcholine species released by phospholipase A hydrolysis were increased. SP-B and SP-C were significantly increased together with some shorter immature forms of SP-B. Surfactant function was impaired and correlated with poor lung aeration. Surfactant nanostructure was significantly damaged in terms of vesicle size, tridimensional complexity, and compactness. Various alterations of surfactant phospholipids and proteins were detected in the early phase of severe meconium aspiration and were due to hydrolysis and inflammation and a defensive response. This impairs both surfactant structure and function, finally resulting in reduced lung aeration. These findings support the development of new surfactant protection and antiinflammatory strategies for severe MAS.
尚无数据表明胎粪对严重胎粪吸入综合征（MAS）早期人类表面活性物质的影响。本研究旨在探讨胎粪损伤早期表面活性物质组成、功能和结构的变化。我们设计了一项非支气管镜 BAL 的转化前瞻性队列研究，纳入了 14 例严重 MAS 新生儿和 18 例无肺部疾病的新生儿。采用液相色谱-高分辨质谱分析表面活性物质脂质。通过 ELISA 检测分泌型磷脂酶 A 亚型 IB、V 和 X 以及 SP-A（表面活性蛋白 A）。在非还原和还原条件下通过 Western 印迹分析 SP-B 和 SP-C。通过吸附试验和俘获气泡表面张力计评估表面活性物质功能，通过半定量肺超声评估肺充气。使用冷冻电镜和原子力显微镜研究表面活性物质的纳米结构。在 MAS 期间检测到几种磷脂亚类的变化。水解磷脂酶 A 释放的溶血磷脂酰胆碱种类增加。SP-B 和 SP-C 显著增加，同时存在一些较短的不成熟 SP-B 形式。表面活性物质功能受损，与肺充气不良相关。表面活性物质纳米结构在囊泡大小、三维复杂性和致密性方面均受到显著损害。在严重胎粪吸入的早期阶段检测到表面活性物质磷脂和蛋白质的各种改变，这些改变归因于水解和炎症以及防御反应。这会损害表面活性物质的结构和功能，最终导致肺充气减少。这些发现支持为严重 MAS 开发新的表面活性物质保护和抗炎策略。
