Lipoxin A4 attenuates the lung ischaemia reperfusion injury in rats after lung transplantation

BACKGROUND: Lung ischaemia reperfusion injury (LIRI) is the major cause of primary lung dysfunction after lung transplantation. Lipoxin A4 inhibits the oxidative stress and inflammation. This study aimed to evaluate the potential protective effect of lipoxin A4 on LIRI in rats. METHODS: SD (Sprague-Dawley) rats were randomised into the sham, LIRI and LA4 groups. Rats in the sham group received anaesthesia, thoracotomy and intravenous injection of saline, while those in the LIRI or LA4 group received left lung transplantation and intravenous injection of saline or lipoxin A4, respectively. After 24 h of reperfusion, the PaO(2)/FiO(2) (Partial pressure of O2 to fraction inspiratory O2), wet/dry weight ratios and protein levels in lungs were measured to assess the alveolar capillary permeability. The oxidative stress response and inflammation were examined. The histological and apoptosis analyses of lung tissues were performed via HE staining (Haematoxylin-eosin staining) and TUNEL assay, respectively. The effects of lipoxin A4 on the endothelial viability and tube formation of hypoxaemia and reoxygenation-challenged rat pulmonary microvascular endothelium cells were determined. RESULTS: Lipoxin A4 significantly ameliorated the alveolar capillary permeability, reduced the oxidative stress and inflammation in transplanted lungs. The histological injury and apoptosis of lung tissues were also alleviated by lipoxin A4. In vitro lipoxin A4 treatment promoted the endothelial tube formation and improved the endothelial viability. CONCLUSION: Lipoxin A4 protects LIRI after lung transplantation in rats, and its therapeutic effect is associated with the properties of anti-inflammation, anti-oxidation, and endothelium protection. KEY MESSAGES: 1. Lung transplantation is a treatment approach for the patients with lung disease. 2. LIRI is the major cause of postoperative primary lung dysfunction. 3. Lipoxins A4 exhibits strong anti-inflammatory properties.