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: Li-da Jin, Liang-Rong Wang, Li-Qin Wu, Yuan-Lu Shan, Xi-Yue Zhao, Xiang-Qing Xiong, Jun-Hui Zhou, Li-Na Lin, Lie-Lie Jin
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 16 Issue 2 Pg. 288-95 (Jun 2013) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 23587488 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Aqp1 protein, rat
• Cyclooxygenase 2 Inhibitors
• Cytokines
• Nitrobenzenes
• RNA, Messenger
• Sulfonamides
• N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
• Aquaporin 1
• Cyclooxygenase 2
• Ptgs2 protein, rat

Topics

• Animals
• Aquaporin 1 (metabolism)
• Bronchoalveolar Lavage Fluid (chemistry)
• Cyclooxygenase 2 (genetics)
• Cyclooxygenase 2 Inhibitors (pharmacology, therapeutic use)
• Cytokines (metabolism)
• Lung (drug effects, metabolism, pathology)
• Lung Injury (drug therapy, etiology, metabolism, pathology)
• Male
• Nitrobenzenes (pharmacology, therapeutic use)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Respiration, Artificial (adverse effects)
• Sulfonamides (pharmacology, therapeutic use)