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BioMed Research International
Volume 2014, Article ID 749097, 11 pages
http://dx.doi.org/10.1155/2014/749097
Research Article

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

1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 252 Wu-Hsing Street, Taipei 110, Taiwan
2Department of Pediatrics, Wan Fang Hospital, Taipei Medical University, No. 111, Section 3, Hsing-Long Road, Taipei 116, Taiwan
3Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 252 Wu-Hsing Street, Taipei 110, Taiwan
4Department of Anatomy, School of Medicine, College of Medicine, Taipei Medical University, 252 Wu-Hsing Street, Taipei 110, Taiwan
5Department of Pediatrics, Taipei Medical University Hospital, 252 Wu-Hsing Street, Taipei 110, Taiwan
6Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, 252 Wu-Hsing Street, Taipei 110, Taiwan

Received 16 February 2014; Revised 15 May 2014; Accepted 19 May 2014; Published 12 June 2014

Academic Editor: Emilia Lecuona

Copyright © 2014 Liang-Ti Huang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.