The Protection Effect of Ulinastatin on Freshwater Instillation-Induced Acute Lung Injury in Rabbits

Abstract Background: Drowning is an important cause of accidental death in humans. The main cause of death following drowning is pulmonary oedema or lung injury, eventually leading to acute respiratory distress syndrome. The present study aimed to determine the protective effects of Ulinastatin on freshwater-induced acute drowning lung injury. Methods: Rabbits were randomly divided into a control, freshwater, freshwater + small-dose Ulinastatin, freshwater + medium-dose Ulinastatin, freshwater + large-dose Ulinastatin group. The arterial blood gas analysis was performed before modelling (baseline) and at various time points after freshwater instillation. And then, the wet-to-dry weight ratio lung permeability index were measured to detect the effect of Ulinastatin on lung endothelial permeability. Furthermore, histopathological staining and ELISAs were used to analyse the histological changes and inflammatory cytokines expression resulted from lung injury, respectively. Western blotting and Quantitative real-time polymerase chain reaction were used to measure the protein and mRNA levels of Hypoxia inducible factor-lα (HIF-1α)/ Vascular endothelial growth factor (VEGF) in the lung tissues. Results: By inhibiting the HIF-1α/VEGF pathway, treatment with Ulinastatin at a large dose could markedly attenuate changes in the PaO2/FiO2 (P/F), lung endothelial permeability, histopathology, and the expression of inflammatory cytokines induced by freshwater instillation. Conclusion: Ulinastatin is a potential candidate treatment for freshwater drowning-induced acute lung injury that targets the HIF-1α/VEGF pathway.