Nintedanib alleviates hyperoxia-induced lung injury via targeting NF-κB signalling pathway in rat model of bronchopulmonary dysplasia.

Introduction: Bronchopulmonary dysplasia (BPD) is a common chronic respiratory disease in premature infants. Hyperoxia is the main pathogenic factor of BPD. Nintedanib is a small-molecule tyrosine kinase inhibitor that has been confirmed to affect several cellular processes in different diseases. The aim of this study was to explore the function of nintedanib in the treatment of BPD.

Material and methods: We used newborn Sprague-Dawley rats (postnatal day 1) to establish an in vivo BPD model by hyperoxia induction. Nintedanib was intraperitoneally injected into rats. Haematoxylin and eosin (H&E) staining was applied to detect lung injury in BPD rats. Cell apoptosis was determined by TUNEL (TdT-mediated dUTP nick end labelling) assay. Western blotting was applied to detect level changes of inflammatory factors IL-1β (interleukin-1 beta), CXCL-1 (C-X-C motif chemokine ligand 1), MCP-1 (monocyte chemotactic protein-1), as well as the phosphorylation of IkB (NF kappa B inhibitor) and NF-kB (nuclear factor kappa-B) in lung samples.

Results: Hyperoxia resulted in lung injury in neonatal rats, while nintedanib treatment relieved the injury. Furthermore, nintedanib alleviated hyperoxia-induced apoptosis in rat lungs. We further observed that an inflammatory response caused by hyperoxia in lung samples was attenuated by nintedanib administration. Additionally, nintedanib inactivated the NF-κB pathway in BPD rats.

Conclusions: Nintedanib alleviates hyperoxia-induced lung injury via targeting the NF-κB signalling pathway.