• Liang-Ti Huang, Chien-Huang Lin, Hsiu-Chu Chou, and Chung-Ming Chen.
• Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 252 Wu-Hsing Street, Taipei 110, Taiwan ; Department of Pediatrics, Wan Fang Hospital, Taipei Medical University, No. 111, Section 3, Hsing-Long Road, Taipei 116, Taiwan.
• Biomed Res Int. 2014 Jan 1;2014:749097.

BackgroundVentilator-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.MethodsTwenty-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.ResultsIbuprofen 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.ConclusionIbuprofen attenuated high tidal volume induced pulmonary endothelial hyperpermeability. This protective effect was associated with a reduced Rho-kinase activity.

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