Ibuprofen Protects Ventilator-Induced Lung Injury by Downregulating Rho-Kinase Activity in Rats

• Published in: BioMed research international 2014-01, Vol.2014 (2014), p.1-11
• Main Authors: Huang, Liang-Ti, Lin, Chien-Huang, Chou, Hsiu-Chu, Chen, Chung-Ming
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Colleges & universities; Down-Regulation - drug effects; Enzyme Activation; Ibuprofen - administration & dosage; Kinases; Lung - drug effects; Lung - metabolism; Male; Rats; Rats, Sprague-Dawley; rho-Associated Kinases - metabolism; Rodents; Treatment Outcome; Ventilator-Induced Lung Injury - enzymology; Ventilator-Induced Lung Injury - prevention & control; Ventilators
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2014/749097

Background. Ventilator-induced lung injury-(VILI-) induced endothelial permeability is regulated through the Rho-dependent signaling pathway. Ibuprofen inhibits Rho activation in animal models of spinal-cord injury and Alzheimer’s disease. The study aims to investigate ibuprofen effects on high tidal volume associated VILI. Methods. Twenty-eight adult male Sprague-Dawley rats were randomized to receive a ventilation strategy with three different interventions for 2 h: (1) a high-volume zero-positive end-expiratory pressure (PEEP) (HVZP) group; (2) an HVZP + ibuprofen 15 mg/kg group; and (3) an HVZP + ibuprofen 30 mg/kg group. A fourth group without ventilation served as the control group. Rho-kinase activity was determined by ratio of phosphorylated ezrin, radixin, and moesin (p-ERM), substrates of Rho-kinase, to total ERM. VILI was characterized by increased pulmonary protein leak, wet-to-dry weight ratio, cytokines level, and Rho guanine nucleotide exchange factor (GEF-H1), RhoA activity, p-ERM/total ERM, and p-myosin light chain (MLC) protein expression. Results. Ibuprofen pretreatment significantly reduced the HVZP ventilation-induced increase in pulmonary protein leak, wet-to-dry weight ratio, bronchoalveolar lavage fluid interleukin-6 and RANTES levels, and lung GEF-H1, RhoA activity, p-ERM/total ERM, and p-MLC protein expression. Conclusion. Ibuprofen attenuated high tidal volume induced pulmonary endothelial hyperpermeability. This protective effect was associated with a reduced Rho-kinase activity.