A long-lasting rat model of hyperoxia-induced acute respiratory distress syndrome: Systematic evaluation and validation.

Acute respiratory distress syndrome (ARDS) is an acute diffuse inflammatory lung injury with high morbidity and mortality. Existing animal models fail to replicate all features of human ARDS pathophysiology. This study aimed to establish a standardised protocol for creating a rat model of hyperoxia-induced ARDS, assess the model's compatibility with ARDS criteria, and evaluate its potential as a long-lasting research model. Thirty-six male Sprague-Dawley rats were exposed to a 95 % O2 environment. At 24, 48, and 72 h, physiological function, lung histopathology, alveolar-capillary barrier function, and inflammatory response of the model were assessed. Simultaneously, micro-CT was performed to observe lung injury progression and analyze radiomic features. Finally, assisted ventilation experiments were conducted to confirm the model's properties. After 48 h, the oxygenation index of rats significantly decreased (p < 0.0001), reaching mild-moderate ARDS level defined by Berlin criteria. Obvious histological changes occurred (p < 0.0001), with the formation of hyaline membranes, which are uncommon in small rodents. The permeability of the alveolar-capillary was significantly increased (p < 0.0001). The levels of TNF-α, IL-1β, and IL-6 were markedly elevated (p < 0.0001), indicating a strong inflammatory response. Micro-CT revealed diffuse lung injury, with increasing injury severity over prolonged hyperoxia exposure (p < 0.01). Radiomic features analysis revealed imaging changes analogous to those observed in ARDS patients. After 7 days of assisted ventilation experiments, model rats survived, and hypoxemia in the control group persisted. This study established a long-lasting rat model of hyperoxia-induced ARDS that aligns with the criteria for ARDS. The model is reproducible, controllable in severity, long-term stable, and non-resolution in injury. It is expected to serve as an important bridge connecting basic research and clinical translation, and offers a practicable preclinical platform for evaluating novel ventilatory strategies, anti-inflammatory/anti-fibrotic therapeutics, and other interventions.