ABSTRACT
Objective To evaluate the role of cyclooxygenase-2 (COX-2) in ventilator-induced lung injury in rats.Methods Thirty healthy adult male Sprague-Dawley rats,aged 3.0-3.5 months,weighing 300-350 g,were randomly divided into 3 groups (n =10 each) using a random number table:traditional tidal volume group (group T,VT =8 ml/kg),large tidal volume group (group L,VT =40 ml/kg) and NS398 (selective COX-2 inhibitor,VT =40 ml/kg) group (group N).In group N,8 mg/kg NS398 (in 2 ml of 10％ dimethyl sulfoxide) was injected intraperitoneally at 1 h before ventilation,while dimethyl sulfoxide 2 ml was administrated instead of NS398 in T and L groups.After 4 h of mechanical ventilation,arterial blood samples were obtained for blood gas analysis and PaO2 was recorded.The animals were sacrificed and lungs removed for microscopic examination and for determination of wet/dry lung weight ratio (W/D ratio) and concentrations of total protein,intercellular adhesion molecule-1 (ICAM-1),tumor necrosis factor-alpha (TNF-α),NO and 6-keto-prostaglandin F1alpha (6-keto-PGF1 α) in bronchoaveolar lavage fluid (BALF).Pulmonary permeability index (PPI) and TXB2/6-keto-PGF1 α ratio were calculated.Results Compared with group T,PaO2 was significantly decreased,W/D ratio and PPI were increased,the total protein,ICAM-1,TNF-α and NO levels and TXB2/6-keto-PGF1 α ratio in BALF were increased in group L(P ＜ 0.05).PaO2 was significantly higher,W/D ratio and PPI were lower,and total protein,ICAM-1,TNF-α and NO levels and TXB2/6-keto-PGF1 α ratio in BALF were lower in group NS than in group L (P ＜ 0.05).The damage to lung tissues was severe in group L,and obviously alleviated in group N.Conclusion COX-2 is involved in ventilator-induced lung injury in rats.