期刊
CRITICAL CARE MEDICINE
卷 40, 期 2, 页码 510-517出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCM.0b013e31822f09d7
关键词
acute lung injury; extracellular matrix; ventilator-induced lung injury
资金
- Ministry of Science of Spain [SAF 2004-06833]
- FUNCIS [53/04, EMER07/001]
- Instituto de Salud Carlos III
- ENCYT [2015]
- Canadian Institutes of Health Research (CIHR) [MOP77818, MOP69042]
- McLaughlin Foundation
- [MOP8558]
Objectives: Many mechanically ventilated patients with acute respiratory distress syndrome develop pulmonary fibrosis. Stresses induced by mechanical ventilation may explain the development of fibrosis by a number of mechanisms (e. g., damage the alveolar epithelium, biotrauma). The objective of this study was t test the hypothesis that mechanical ventilation plays an important role in the pathogenesis of lung fibrosis. Methods: C57BL/6 mice were randomized into four groups: healthy controls; hydrochloric acid aspiration alone; vehicle control solution followed 24 hrs later by mechanical ventilation (peak inspiratory pressure 22 cm H2O and positive end-expiratory pressure 2 cm H2O for 2 hrs); and acid aspiration followed 24 hrs later by mechanical ventilation. The animals were monitored for up to 15 days after acid aspiration. To explore the direct effects of mechanical stress on lung fibrotic formation, human lung epithelial cells (BEAS-2B) were exposed to mechanical stretch for up to 48 hrs. Measurement and Main Results: Impaired lung mechanics after mechanical ventilation was associated with increased lung hydroxyproline content, and increased expression of transforming growth factor-beta, beta-catenin, and mesenchymal markers (alpha-smooth muscle actin and vimentin) at both the gene and protein levels. Expression of epithelial markers including cytokeratin-8, E-cadherin, and prosurfactant protein B decreased. Lung histology demonstrated fibrosis formation and potential epithelia-mesenchymal transition. In vitro direct mechanical stretch of BEAS-2B cells resulted in similar fibrotic and epithelia-mesenchymal transition formation. Conclusions: Mechanical stress induces lung fibrosis, and epithelia-mesenchymal transition may play an important role in mediating the ventilator-induced lung fibrosis. (Crit Care Med 2012; 40:510-517)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据