title: Ibuprofen protects ventilator-induced lung injury by downregulating Rho-kinase activity in rats.
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.
  
  
  CONCLUSIONS
  Ibuprofen attenuated high tidal volume induced pulmonary endothelial hyperpermeability. This protective effect was associated with a reduced Rho-kinase activity.
authors.affiliation: 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.
authors.forename: Liang-Ti
authors.identifier: 0000-0001-6451-6282
authors.initials: LT
authors.lastname: Huang
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 252 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: Chien-Huang
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Anatomy, School of Medicine, College of Medicine, Taipei Medical University, 252 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: Hsiu-Chu
authors.initials: HC
authors.lastname: Chou
authors.affiliation: Department of Pediatrics, Taipei Medical University Hospital, 252 Wu-Hsing Street, Taipei 110, Taiwan ; Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, 252 Wu-Hsing Street, Taipei 110, Taiwan.
authors.forename: Chung-Ming
authors.identifier: 0000-0001-8762-8957
authors.initials: CM
authors.lastname: Chen
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation; D007052:Ibuprofen / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D055397:Ventilator-Induced Lung Injury / Q000201:enzymology* / Q000517:prevention & control*; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D054460:rho-Associated Kinases; D007052:Ibuprofen