Manji Aminmohamed, Wang Lefeng, Pape Cynthia M, McCaig Lynda A, Troitskaya Alexandra, Batnyam Onon, McDonald Leah Jj, Appleton C Thomas, Veldhuizen Ruud Aw, Gill Sean E
Centre for Critical Illness Research, London Health Sciences Centre Research Institute, London, Ontario, Canada.
Department of Physiology and Pharmacology.
JCI Insight. 2025 Feb 13;10(6):e185834. doi: 10.1172/jci.insight.185834.
Acute respiratory distress syndrome (ARDS) results in substantial morbidity and mortality, especially in elderly people. Mechanical ventilation, a common supportive treatment for ARDS, is necessary for maintaining gas exchange but can also propagate injury. We hypothesized that aging leads to alterations in surfactant function, inflammatory signaling, and microvascular permeability within the lung during mechanical ventilation. Young and aged male mice were mechanically ventilated, and surfactant function, inflammation, and vascular permeability were assessed. Additionally, single-cell RNA-Seq was used to delineate cell-specific transcriptional changes. The results showed that, in aged mice, surfactant dysfunction and vascular permeability were significantly augmented, while inflammation was less pronounced. Differential gene expression and pathway analyses revealed that alveolar macrophages in aged mice showed a blunted inflammatory response, while aged endothelial cells exhibited altered cell-cell junction formation. In vitro functional analysis revealed that aged endothelial cells had an impaired ability to form a barrier. These results highlight the complex interplay between aging and mechanical ventilation, including an age-related predisposition to endothelial barrier dysfunction, due to altered cell-cell junction formation, and decreased inflammation, potentially due to immune exhaustion. It is concluded that age-related vascular changes may underlie the increased susceptibility to injury during mechanical ventilation in elderly patients.
急性呼吸窘迫综合征（ARDS）会导致严重的发病率和死亡率，在老年人中尤为如此。机械通气是ARDS常见的支持性治疗手段，对于维持气体交换是必要的，但也可能会加重损伤。我们推测，衰老会导致机械通气期间肺内表面活性物质功能、炎症信号传导和微血管通透性发生改变。对年轻和老年雄性小鼠进行机械通气，并评估表面活性物质功能、炎症和血管通透性。此外，利用单细胞RNA测序来描绘细胞特异性转录变化。结果显示，在老年小鼠中，表面活性物质功能障碍和血管通透性显著增强，而炎症反应则不那么明显。差异基因表达和通路分析表明，老年小鼠的肺泡巨噬细胞炎症反应减弱，而老年内皮细胞的细胞间连接形成发生改变。体外功能分析显示，老年内皮细胞形成屏障的能力受损。这些结果突出了衰老与机械通气之间复杂的相互作用，包括由于细胞间连接形成改变而导致的与年龄相关的内皮屏障功能障碍易感性增加，以及可能由于免疫耗竭导致的炎症反应减弱。研究得出结论，与年龄相关的血管变化可能是老年患者机械通气期间易受损伤的原因。
