| Objective:Through establishing a neonatal rats model of hyperoxia-induced lung injury and administrating the rosiglitazone then to compare with normal neonatal rats:Methods: One hundred and eight neonatal rats were randomly assigned to three groups at 48 hours after the birth:Group Ⅰ :control group;Group Ⅱ :hyperoxia group(hyperoxia+NS);Group Ⅲ: rosiglitazone group(hyperoxia+ rosiglitazone);The rats of Group Ⅰwere exposed to normoxia(room air) and the rats of group Ⅱ、Ⅲ were exposed to hyperoxia(90-95% oxygen)in a specially constructed boxes.The rats in the group Ⅲ were injected rosiglitazone(3mg/kg),once a day for 7 consecutive days from the beginning of hyperoxia exposure.The rats in the group Ⅰand group Ⅱ were injected with the same volume of normal saline, once a day for 7 consecutive days.Each group was divided into 3 subgroups,the 1-day,3-day and 7-day.Twelve rats from each subgroup were randomly selected,and killed to measure the following indices:(1) The total protein concentration in BALF;(2) Lung wet-to-dry ratio:The left lung were isolated and weighed,then the dried lungs were weighed,and calculated the lung wet/dry ratio;(3) Lung histology:Lung sections from the right lung were stained with HE,and examined for the histological changes;(4) The protein and m RNA expression of Smad3, PPAR-γ:Western blotting and RT-PCR were used to detect the protein and m RNA expression of Smad3, PPAR-γ;Results: 1.The general condition of the rats in each group:Control group, the growth of rats was in normal,and no death.Hyperoxia group,at 1 day of hyperoxia exposure,the rats’ complexion was ruddy,have no dyspnoea without hyperoxia.At 3 days,the respiratory rate of rats accelerated without hyperoxia.At 7 days,the experimental animals’ spirit was dispirited,showed dyspnoea,cyanotic,individual rats died in the absence of hyperoxia.The general condition of rats in rosiglitazone group compared with hyperoxia group was improved.2. The pathological morphology of lung tissue: No pathological change were found in the lung of rats in normoxic controls,the alveolar contain no cells and exudation.While the hyperoxia group,at 1day,alveolar walls were complete,a small amount of redblood cells in the alveoli were seen,without obvious exudation.At 3 days,vascular congestion, interstitial edema and redblood,inflammatory infiltrates were found.At 7 days, pulmonary edema, structure turbulence of the pulmonary tissue,severe hemorrhage, exudation, inflammatory infiltrates were seen.The exudation,cell infiltration in alveolar cavity were obviously decreased in rosiglitazone group compared with hyperoxia group.3. The lung wet/dry ratio : At first experimental day,there was no significant difference in lung W/D ration among the three groups.After 3 and 7 day of hyperoxia,the lung W/D ration of rats was higher in the hyperoxia groups compared with the control group,and the lung W/D ration in the rosiglitazone group was lower than that in the hyperoxia group(P<0.01).4. The total protein concentration in BALF:There was insignificant difference in the TP of BALF among the three groups at experimental day 1(P>0.05).At days 3 and 7,the TP concentration in the BLAF of rats exposed to hyperoxia was significantly higher than that in the normoxia control group,and the TP of BALF in the rosiglitazone group was lower than that in the hyperoxia group(P<0.01).5. The expression of Smad3, PPAR-γ protein in lung tissue:There was no marked difference in the expression of Smad3, PPAR-γ among the three groups at days 1(P>0.05). At days 3,7, Smad3 protein expression in the hyperoxia group was significantly increased as compared with that in the normoxia control group(P<0.01). PPAR-γ protein expression in the hyperoxia group was significantly decreased as compared with that in the normoxia control group(P<0.01).The level of PPAR-γ protein expression in rosiglitazone group was higher than that in hyperoxia group, with statistical significance(P<0.01).6. The expression of AQP1,Na+-K+-ATPase α1,NKCC1 m RNA in lung tissue: There was no marked difference in the expression of Smad3, PPAR-γ among the three groups at days 1(P>0.05). At days 3,7, Smad3 m RNA expression in the hyperoxia group was significantly increased as compared with that in the normoxia control group(P<0.01). PPAR-γ m RNA expression in the hyperoxia group was significantly decreased as compared with that in the normoxia control group(P<0.01).The level of PPAR-γ m RNA expression in rosiglitazone group was higher than that in hyperoxia group, with statistical significance(P<0.01).Conclusion: 1.Neonatal rats were exposed to a high-oxygen environment for a certain period of time developed acute lung injury.The main pathological changes of the lung tissues are local hyperemia, hemorrhage, inflammatory exudates, structure turbulence of the pulmonary tissue,with severe inflammatory cell aggregation.2. The expression of Smad3 protein and m RNA in the lung of rats with acute hyperoxia-induced lung injury increased significantly compared with those in room air,which coincided with the degrees of pulmonary injured. The expression of PPAR-γ protein and m RNA in the lung of rats with acute hyperoxia-induced lung injury increased significantly compared with those in room air which negative correlation with the degrees of pulmonary injured.3. rosiglitazone improved pulmonary injured via up-regulation of PPAR-γ protein and m RNA expression,and provided protection from acute hyperoxia-induced lung injury.However,the mechanism is not clear yet,further study is needed. |
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