ABSTRACT
OBJECTIVE：To compare the protective effect of atomization inhalation and intraperitoneal injection of edaravone on acute lung injury in smoke inhalation lung injury model rats. METHODS ：Thirty male SD rats were divided into normal control group（group A ），injury group （group B ），intraperitoneal injection group （group C ），low-dose aerosol inhalation group （group D），high-dose aerosol inhalation group （group E ）according to random numble table ，with 6 rats in each group. Group B-E were placed in smoke generator containing pine sawdust to induce smoke inhalation lung injury model. In group A ，the operation was the same as above except that the pine sawdust was not placed. Thirty minutes after modeling ，group C were injected intraperitoneally with edaravone 18 mg/kg（every 70 min，4 times in total ）. Group D and E inhaled edaravone 9，1.8 mg/kg（every 60 min，lasting for 10 min each time ，4 times in total ）. The rats were treated by no means in group A and group B. Six hours after last medication，arterial blood gas analysis was performed ，and the lung wet to dry ratio （W/D）and water content of lung tissue were calculated. The levels of TNF-α，IL-6 and IL- 10 in serum were detected by double antibody ELISA. The contents of MDA ，MPO， SOD and Caspase- 3 in lung tissue were determined by ELISA and other methods. HE staining was used to observe the pathological changes of lung tissue. The apoptotic rate of cells in lung tissue were determined by TUNEL assay. RESULTS ：No abnormality was found in lung tissue of group A ；in group B ，hemorrhage and edema were found in lung tissue ，alveolar structure was difficult to identify，and inflammatory cells and red blood cell infiltration were seen. Above symptoms of rats in group C-E were improved to different extent. Compared with group A ，PaO2/FiO2 and SOD content of lung tissue were decreased significantly in other groups （P＜0.05）；water content of lung tissue ，W/D，serum contents of TNF-α，IL-6 and IL- 10，the contents of MDA ，MPO and Caspase-3 in lung tissue ，apoptotic rate were increased significantly （P＜0.05）. Compared with group B ，PaO2/FiO2 and serum contents of IL- 10 were increased significantly in administration groups （P＜0.05）；water content of lung tissue ，W/D，serum contents of TNF-α and IL-6，the contents of MDA ，MPO and Caspase- 3 in lung tissue ，apoptotic rate were significantly decreased，in dose-dependent manner （P＜0.05）. CONCLUSIONS ：Edaravone has a certain protective effect on smoke inhalation lung injury model rat. It can reduce the production and release of inflammatory mediators and/or cytokines ，reduce the peroxide damage and inhibit cell apoptosis in a dose-dependent manner. The effect of atomization inhalation is more obvious than that of intraperitoneal injection.
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(1 mL/kg)in all experimental groups. NS group was identical to the other three groups except that saline(1 mL/kg)was administered instead of LPS. Lipid emulsion(20%,1 mL/kg)or FA injection(1 mL/kg,10 mg/mL)was intravenously injected via vena caudalis 1 hour before LPS in Lip+LPS and FA+LPS groups, respectively. Rats were sacrificed at 1 h, 6 h, 12 h and 24 h after LPS injection and assigned to 1 h, 6 h, 12 h and 24 h subgroups(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-α and PPAR-γ in 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-α and PPAR-γ in the lung tissues of LPS group were significantly lower than those of NS group(P< 0.05). The serum concentration of TNF-α of LPS group was significantly higher than that of NS group (P<.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 semi-quantitative pathological score of lung was signficanlty lower in FA+LPS group than those in LPS and Lip+LPS group at 6 h, 12 h and 24 h after injection(P< 0.05). The mRNA levels of PPAR-α and PPAR-γ in rat lung tissues of FA+LPS group were signficanlty higher than those of LPS and Lip+LPS groups at all times, especially, at 6 h after the intravenous injection of LPS(P< 0.05). The serum concentration of TNF-α of FA+LPS group was significantly lower than that of LPS and Lip+LPS groups at all times, expecially, at 1 h after the intravenous injection of LPS (P<.05). Conclusion FA preconditioning can alleviate the inflammation and protect inhalation injury to lung tissues induced by LPS in rats, which may involve the up-regulation of PPAR-α andPPAR-γ mRNA levels in rat lung tissues and the down-regulation of serum TNF-α.