Effect of inhaled aerosolized budesonide and salbutamol on HIF-1α/VEGF signaling pathway in collapsed lung tissues of rabbits undergoing one-lung ventilation

Abstract

Objective To evaluate the effect of inhaled aerosolized budesonide and salbutamol on hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway in collapsed lung tissues of rabbits undergoing one-lung ventilation (OLV). Methods Twenty-four healthy male New Zealand white rabbits, aged 5-6 months, weighing 2.5-3.0 kg, were randomized into 3 groups (n=8 each) using a random number table method: two-lung ventilation (TLV) group, OLV group, and budesonide and salbutamol aerosol inhalation group (group B+ S). Bilateral lungs were ventilated for 3 h in group TLV, and the left lung was ventilated for 2 h followed by 1-h TLV in group OLV and B+ S group.In group B+ S, aerosolized salbutamol 0.15 mg/kg and budesonide 1 mg in normal saline (2 ml in total) was inhaled before OLV.The equal volume of normal saline was given instead in TLV and OLV groups.Volume-controlled ventilation was used in each group.Before beginning of aerosol inhalation (T0), immediately after the end of aerosol inhalation (T1), and at 1, 2 and 3 h of ventilation (T2-4), arterial blood samples were obtained for blood gas analysis.Oxygenation index was calculated.The rabbits were sacrificed at the end of ventilation, and lower lobe tissues were obtained from the collapsed lung for examination of the pathological changes (with a light microscope) which were scored and for determination of HIF-1α and VEGF expression in lung tissues (by Western blot). Results Compared with group TLV, oxygenation index was significantly decreased at T2-4, the concentration of lactic acid and lung injury score were increased, and the expression of HIF-1α and VEGF was up-regulated in group OLV and group B+ S (P<0.05). Compared with group OLV, oxygenation index was significantly increased at T2-4, the concentration of lactic acid and lung injury score were decreased, and the expression of HIF-1α and VEGF was down-regulated in group S+ B (P<0.05). Conclusion The mechanism by which inhaled aerosolized budesonide and salbutamol reduces OLV-induced injury to the collapsed lung is related to blocking HIF-1α/VEGF signaling pathway in lung tissues of rabbits. Key words: One-lung ventilation; Acute lung injury; Budesonide; Albuterol; Bronchodilator agents; Administration, inhalation