Influence of different dosages of dexamethasone on bleomycin-induced lung fibrosis in rats

Objective To observe the therapeutic and side effect of different dosages of dexamethasone(DXM)on bleomycin-induced lung fibrosis in rats and to investigate the effective and safe dosage of DXM on lung fibrosis models.Methods144 healthy male Sprague-Dawley(SD)rats were randomly divided into four groups including control group(n=18),DXM side effect group(n=54),model group(n=18)and DXM treated group(n=54).DXM side effect group and DXM treated group were then divided into three subgroups respectively(18 rats in each subgroup)according to different dosages of DXM including 1 mg/kg,2 mg/kg and 3 mg/kg subgroup.Finally,each group was divided into three groups randomly(6 rats each group),which were sacrificed on 14 d,28 d and 56 d.Survival analysis was done and HE staining was performed on the left lung tissue sections to observe the extent of alveolitis and fibrosis.Hydroxyproline(HYP)assays of the right lung tissue of rats in the control group,the model group and DXM treated group were also made to estimate the collagen content.The liver and kidney tissue sections were got HE stained to observe the structure and inflammation.ResultsThe death rate by 56 d of 3 mg/kg DXM side effect group and the treated group was significantly higher as compared to that of homologous the control group,model group,1 mg/kg DXM side effect group and the treated group(P0.05).The alveolitis and fibrosis induced by bleomycin could be relieved by DXM in some extent,while the infection rate was higher with the increase of its dosage and treated durations,and no more improvement was shown on lung fibrosis.HYP analysis showed that most of the treated groups had a lower content of collagen than the homologous model groups and there was no significant difference of HYP among the treated groups which were treated by three different dosages of DXM respectively.The livers in the DXM side effect groups and the treated groups got fatty degeneration generally,and the renal tubules in the above groups suffered infection.Conclusion1 mg/kg DXM is an effective and safe choice to ameliorate the formation of bleomycin-induced lung fibrosis in rats,which wouldn't result in serious infection and high death rate.