title: Effects of COX-2 inhibitor on ventilator-induced lung injury in rats.
abstract: BACKGROUND
  Mechanical ventilation especially with large tidal volume has been demonstrated to activate inflammatory response inducing lung injury, which could be attenuated by cyclooxygenase (COX)-2 inhibitors. As the main small integral membrane proteins that selectively conduct water molecules' transportation, aquaporin (AQP)-1 downregulation significantly related to lung edema and inflammation. This study aims to investigate the role of AQP1 in ventilator-induced lung injury in rats and evaluates the effects of COX-2 inhibition.
  
  
  METHODS
  Forty rats were allocated into four groups, where rats in Groups LD (low volume+DMSO) and LN (low volume+NS-398) were given intravenously 2ml DMSO and 8mg/kg NS-398 (a specific COX-2 inhibitor, dissolved in 2ml DMSO) before 4-hour lower tidal volume ventilation (8ml/kg), respectively, while DMSO and NS-398 were administrated in the same manner before 4-hour injurious ventilation (40ml/kg) in Groups HD (high volume+DMSO) and HN (high volume+NS-398). The arachidonic acid metabolites (6-keto prostaglandin F1α, thromboxane B2), inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, 6, 8) and total protein levels in bronchoalveolar lavage (BAL) fluid and COX-2 mRNA and AQP1 protein expression in lung tissue were detected; water content and lung morphology were also evaluated.
  
  
  RESULTS
  Compared to Groups LD and LN, the rats in Groups HD and HN suffered obvious lung morphological changes with higher wet-to-dry weight ratio and lung injury score, and the levels of arachidonic acid metabolites, inflammatory cytokines and total protein in BAL fluid were increased, the expression of COX-2 mRNA was significantly upregulated and AQP1 protein was downregulated in lung tissue (p<0.05). The changes in BAL fluid and the severity of lung injury were attenuated, and AQP1 expression was upregulated in Group HN as compared to HD (p<0.05).
  
  
  CONCLUSIONS
  Ventilation with large tidal volume causes inflammatory mediator production and AQP1 downregulation, which could be attenuated by COX-2 inhibition.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou City, China.
authors.forename: Li-da
authors.initials: LD
authors.lastname: Jin
authors.forename: Liang-Rong
authors.initials: LR
authors.lastname: Wang
authors.forename: Li-Qin
authors.initials: LQ
authors.lastname: Wu
authors.forename: Yuan-Lu
authors.initials: YL
authors.lastname: Shan
authors.forename: Xi-Yue
authors.initials: XY
authors.lastname: Zhao
authors.forename: Xiang-Qing
authors.initials: XQ
authors.lastname: Xiong
authors.forename: Jun-Hui
authors.initials: JH
authors.lastname: Zhou
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Lin
authors.forename: Lie-Lie
authors.initials: LL
authors.lastname: Jin
mesh_terms: D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C496022:Aqp1 protein, rat; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051398:Aquaporin 1; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat