Dexamethasone alleviates acute lung injury in a rat model with venovenous extracorporeal membrane oxygenation support

• Published in: BMJ open respiratory research 2024-12, Vol.11 (1), p.e002394
• Main Authors: Wei, Shi-Lin, Du, Jun-Zhe, Zhai, Ke-Rong, Yang, Jian-Bao, Zhang, Ran, Wu, Xiang-Yang, Li, Yongnan, Li, Bin
• Format: Article
• Language: English
• Subjects: A549 Cells; Acute Lung Injury - etiology; Acute Lung Injury - therapy; Alveolar Epithelial Cells - drug effects; Alveolar Epithelial Cells - metabolism; Animals; Antibodies; COVID-19; Cytokeratin; Cytokines; Cytokines - metabolism; Dexamethasone - pharmacology; Dexamethasone - therapeutic use; Disease Models, Animal; Edema; Extracorporeal membrane oxygenation; Extracorporeal Membrane Oxygenation - methods; Hippo Signaling Pathway; Humans; Inflammation; Male; Manufacturers; Mortality; Oleic Acid; Original Research; Rats; Rats, Sprague-Dawley; Respiratory distress syndrome; Respiratory Research; SARS-CoV-2; Signal Transduction; Surfactants; Ventilation; Ventilators; YAP-Signaling Proteins
• ISSN: 2052-4439; 2052-4439
• DOI: 10.1136/bmjresp-2024-002394

In recent years, dexamethasone (Dex) has been used to treat acute respiratory distress syndrome (ARDS) in patients with COVID-19 and achieved promising outcomes. Venovenous extracorporeal membrane oxygenation (VV ECMO) support for patients with ARDS has increased significantly worldwide. However, it remains unknown whether Dex could improve the efficiency of VV ECMO to reduce lung injury. Here, we investigate the combined efficiency of VV ECMO and Dex in rats with acute lung injury (ALI). We established VV ECMO in oleic acid (OA)-treated ALI rats and administered Dex. We conducted HE staining and evaluated lung and bronchoalveolar lavage (BAL) fluid cytokines to assess lung injury and inflammation. Furthermore, we investigated the activation of Hippo/YAP signalling in alveolar epithelial type II cell (AT2)-mediated alveolar epithelial repair using quantitative PCR, Western blotting and immunofluorescence. In vitro, the human alveolar epithelial cell line A549 was used to investigate the key role of YAP in alveolar epithelial cell differentiation. VV ECMO combined with Dex alleviated OA-induced lung injury and pulmonary inflammation. Pulmonary oedema and exudation were significantly alleviated, and the lung and BAL levels of IL-6, IL-8 and TNF-α were significantly reduced compared with those observed with ECMO alone. In addition, VV ECMO combined with Dex treatment protected alveolar epithelial cells by activating Hippo/YAP signalling. In vitro, Dex promoted YAP expression and alveolar epithelial cell differentiation, whereas YAP knockdown inhibited YAP-mediated differentiation. Our findings suggest that adjuvant Dex treatment during VV ECMO could alleviate ALI and pulmonary inflammation by activating the Hippo/YAP signalling pathway, which promoted alveolar regeneration and AT2 differentiation.