Effects of rosiglitazone on pulmonary injury of septic rats induced by cecal ligation puncture

Abstract

Objective To observe the effects of rosiglitazone,an agonist of peroxisome proliferator-activated receptor γ (PPARγ),on pulmonary injury in septic rats induced by cecal ligation puncture(CLP).Methods Eighty healthy male Wistar rats were randomly divided into 5 groups:sham group (group SHAM),cecal ligation puncture group (group CLP).rosiglitazone group (group ROSI),in which rats were intravenous injected with rosiglitazone 0.3 mg/kg 30 min before CLP.GW9662 group (group GW),in which rats were intravenous injected with GW9662 0.3 mg/kg 30 m in before CLP.GW9662 plus rosiglitazone group (group GW+ROSI),in which rats were injected intravenously with GW9662 0.3 mg/kg 30 min before CLP and then with rosiglitazone 0.3mg/kg 15 min before CLP.Eight rats were sacrificed at 6 and 24 h after CLP respectively in each group.Plasma was collected for the measurement of the level of plasma tumor necrosis factor-α (TNF-α) by enzyme linked immunosorbent assay (ELISA) and lung tissues were harvested for the detections of lung wet/dry (W/D) ratio,lung myeloperoxidase (MPO) activity,and lung tissue high mobility group protein B1 (HMGB1) mRNA expression by real-time PCR.Results The lung W/D ratio,MPO activity,plasma TNF-α level and the lung tissue HMGB1 mRNA expression of group CLP,group ROSI,group GW and group GW+ROSI were significantly higher than that of group SHAM.The lung W/D ratio,MPO activity,plasma TNF-α level and the lung tissue HMGB1 mRNA expression of group CLP [(5.31±0.14),(3.15±0.47) U/g,(15.064±0.448) μg/L and (0.758± 0.130)],group ROSI [(4.33±0.21),(2.21±0.31) U/g,(3.334±0.212) μg/L and (0.422±0.124)],group GW[(4.93±0.14),(3.13± 0.28) U/g,(15.001±0.343)μg/L and (0.732±0.198)] and group GW+ROSI[(4.87±0.13),(3.08±0.35) U/g,(14.866±0.412) μg/L and (0.763±0.017)] at 6 hafter CLP were significantly higher than that of the group SHAM[(3.98±0.17),(0.67±0.43) U/g,(0.452±0.033) μg/L and (0.244±0.053)](P＜0.05).At 24 h after CLP,the lung W/D ratio,MPO activity,plasma TNF-α level and the lung tissue HMGB1 mRNA expression of group CLP[(10.23±0.19),(3.61±-0.82) U/g,(1.542±0.193) μg/L and (2.413±0.211)],group ROS[(6.39±0.18),(2.17±1.02) U/g,(0.947±0.281) μg/L and (1.517±0.076)],group GW[(10.08±0.26),(3.45±0.36) U/g,(1.513±0.210).μg/L and (2.385±0.323)] and group GW+ROSI[(10.15±0.18),(3.53±0.32) U/g,(1.524±0.180) μg/L and (2.404±0.135)] were significantly higher than that of the group SHAM[(4.02±0.20),(0.68±0.34) U/g,(0.429±0.021) μg/L and (0.232±0.032)] (P＜0.05).The lung W/D ratio,MPO activity,plasma TNF-α level and the lung tissue HMGB1 mRNA expression of group ROSI were significantly lower than that of group CLP,group GW and group GW+ROSI respectively (P＜0.05).Conclusions Rosiglitazone can decrease the plasma TNF-α level and the lung tissue HMGB1 mRNA expression level and attenuate the pulmonary edema and inflammation in septic rats induced by CLP.It may have protective function against pulmonary injury. Key words: Sepsis; Pulmonary injury; Rosiglitazone