Flurbiprofen axetil preconditioning allivates inhalation lung injury in rats

Abstract

Objective To investigate the protective effects of flurbiprofen axetil(FA)on inhalation lung injury induced by lipopolysaccharides(LPS)inhalation in rats,so as to provide evidence for applying FA in treating inhalation lung injury in clinic.Methods A total of 96 adult male Sprague-Dawley rats were evenly randomized into four groups(n=24):saline negative control group(NS group),model group(LPS group),lipid emulsion preconditioning control group(Lip+LPS group),and FA preconditioning group(FA+LPS group).The model of inhalation lung injury was established with endotracheal instillation of LPS(1mL/kg)in all experimental groups.NS group was identical to the other three groups except that saline(1mL/kg)was administered instead of LPS.Lipid emulsion(20%,1mL/kg)or FA injection(1mL/kg,10mg/mL)was intravenously injected via vena caudalis 1hour before LPS in Lip+LPS and FA+LPS groups,respectively.Rats were sacrificed at 1h,6h,12hand24 hafter LPS injection and assigned to 1h,6h,12 hand 24hsubgroups(n=6).The arterial blood gas was analyzed and the lungs were removed for determination of the wet/dry mass(W/D)ratio and evaluation of histological injury in all groups.Real-time PCR was used to detect the mRNA levels of PPAR-αand PPAR-γin rats lung homogenates.The concentration of tumor necrosis factor-alpha(TNF-α)in rat serum was determined by ELISA.Results The rats in LPS and Lip+LPS groups showed damaged structure of lung tissue and inflammation.The mRNA levels of PPAR-αand PPAR-γin the lung tissues of LPS group were significantly lower than those of NS group(P0.05).The serum concentration of TNF-αof LPS group was significantly higher than that of NS group(P0.05).The pulmonary lesions in FA+LPS group were ameliorated compared with those in LPS and Lip+LPS groups.Pressure of oxygen in arterial blood(PaO2)was signficantly higher and semiquantitative pathological score of lung was signficanlty lower in FA+LPS group than those in LPS and Lip+LPS group at 6h,12 hand 24hafter injection(P0.05).The mRNA levels of PPAR-αand PPAR-γin rat lung tissues of FA+LPS group were signficanlty higher than those of LPS and Lip+LPS groups at all times,especially,at 6hafter the intravenous injection of LPS(P0.05).The serum concentration of TNF-αof FA+LPS group was significantly lower than that of LPS and Lip+LPS groups at all times,expecially,at 1hafter the intravenous injection of LPS(P0.05).Conclusion FA preconditioning can alleviate the inflammation and protect inhalation injury to lung tissues induced by LPS in rats,which may involve the upregulation of PPAR-αand PPAR-γ mRNA levels in rat lung tissues and the down-regulation of serum TNF-α.