Hirdman Gabriel, Stenlo Martin, Bèchet Nicholas Burdon, Niroomand Anna, Mittendorfer Margareta, Wang Qi, Edström Dag, Ghaidan Haider, Kjellström Sven, Pierre Leif, Olm Franziska, Hyllén Snejana, Lindstedt Sandra
Department of Cardiothoracic Anaesthesia and Intensive Care and Cardiothoracic Surgery and Transplantation, Skåne University Hospital, Lund University, Lund, Sweden.
Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.
Transplantation. 2025 Jul 1;109(7):1166-1174. doi: 10.1097/TP.0000000000005353. Epub 2025 Feb 19.
Lung transplantation remains hampered by a scarcity of viable donor lungs, partially attributed to donor lung injuries.
Three porcine lung injury models were studied: infection-induced using lipopolysaccharide (n = 7), aspiration-induced using endotracheal gastric content (n = 7), and injury using lavage and harmful ventilation (ventilator-induced lung injury; n = 7). Molecular and functional changes from before and after the establishment of lung injury were examined with histopathology, immunohistochemistry, cytokine levels, hemodynamics, and mass spectrometric analysis of lung tissue. The respiratory tract lining fluid was analyzed using exhaled breath particles.
T-cell proliferation and suppression of complement activation were unique to the gastric injury, whereas the ventilator-induced lung injury group displayed a unique activation of monocyte chemotaxis. The lipopolysaccharide injury exhibited an activation of stress response proteins. Alterations in the extracellular matrix, particularly the degradation of collagen type IV and increased elastin expression, were identified as a consistent indicator of acute lung injury. Additionally, increases in exhaled particles and differential expression of proteins in the respiratory tract lining fluid correlated with deteriorating lung function.
Molecular analysis of the lung indicated distinct key differences and similarities of donor lung injury phenotypes. Analysis of various donor lung injuries suggests a heightened emphasis on the extracellular matrix for the restoration and rejuvenation of damaged donor lungs.
肺移植仍然受到可用供体肺稀缺的阻碍，部分原因是供体肺损伤。
研究了三种猪肺损伤模型：使用脂多糖诱导感染（n = 7）、使用气管内胃内容物诱导误吸（n = 7）以及使用灌洗和有害通气诱导损伤（呼吸机诱导的肺损伤；n = 7）。通过组织病理学、免疫组织化学、细胞因子水平、血流动力学以及肺组织的质谱分析，检查肺损伤建立前后的分子和功能变化。使用呼出的呼吸颗粒分析呼吸道内衬液。
T细胞增殖和补体激活的抑制是胃损伤所特有的，而呼吸机诱导的肺损伤组表现出单核细胞趋化的独特激活。脂多糖损伤表现出应激反应蛋白的激活。细胞外基质的改变，特别是IV型胶原的降解和弹性蛋白表达的增加，被确定为急性肺损伤的一致指标。此外，呼出颗粒的增加和呼吸道内衬液中蛋白质的差异表达与肺功能恶化相关。
对肺的分子分析表明供体肺损伤表型存在明显的关键差异和相似之处。对各种供体肺损伤的分析表明，应更加重视细胞外基质以恢复和修复受损的供体肺。
