Effect Of Mifepristone On The Development Of Pulmonary Fibrosis Induced By Lipopolysaccharide In Rats

Background: Pulmonary fibrosis is caused by a variety of pathogenic factors,fibroblast proliferation and fibrous tissue hyperplasia accompanied by lung tissue inflammatory damage,structural damage as a pathological feature,with a progressive exacerbation of dyspnea as a major clinical manifestation Pulmonary interstitial disease.According to whether the cause is clear,pulmonary fibrosis can be divided into secondary pulmonary fibrosis and idiopathic pulmonary fibrosis.Among them,idiopathic pulmonary fibrosis is the majority.It is currently believed that the occurrence of pulmonary fibrosis is associated with repeated damage and repair of alveolar epithelial cells,as well as epithelial-mesenchymal transition(EMT).The alveolar epithelial cells after injury can also be abnormally activated,secreting many cytokines and inflammatory mediators to participate in the proliferation of fibroblasts,inducing their differentiation into myofibroblasts,and promoting the production of a large number of extracellular matrices,causing the loss of normal lung structure.Abnormally activated alveolar epithelial cells lose normal epithelial regeneration and undergo epithelial-mesenchymal transition(EMT),resulting in the conversion of alveolar epithelial cells into migratory and invasive mesenchymal cells.It causes collagen-producing fibroblasts and myofibroblasts to accumulate,ultimately promoting the development of pulmonary fibrosis.In recent years,the incidence of pulmonary fibrosis has increased.Objective: To investigate the effect of mifepristone on lipopolysaccharide-induced pulmonary fibrosis in rats.Methods: Thirty healthy male SD rats of 8 weeks old were selected and fed in a clean environment.The rats were randomly divided into 3 groups: normal control group,lipopolysaccharide group and mifepristone group(mifepristone + lipopolysaccharide),10 in each group.Rats in the mifepristone group were continuously intragastrically administered with mifepristone(40 mg/kg)for 4 weeks.Rats in the normal control group and the lipopolysaccharide group were intragastrically administered with the same amount of normal saline for 4 weeks.Four weeks later,rats in the lipopolysaccharide and mifepristone group were given lipopolysaccharide nasal drops(10 mg/kg)to establish a model of acute lung injury pulmonary fibrosis.Rats in the normal control group were given nasal drops with the same amount of normal saline.After 2 weeks,the rats were sacrificed and the body weight of the rats was weighed.Rats lung tissues was taken and the lung weight was weighed.Then,the right lung tissues of the rats was fixed in 4% paraformaldehyde and embedded in paraffin to make a 5um thickness slice.Rat abdominal aorta blood was taken with anticoagulation tube and sent to the Department of Clinical Laboratory of the First Affiliated Hospital of Guangxi Medical University for blood routine testing.The lung weight-to-weight ratio(lung weight/body weight)of rats was calculated;the expression of neutrophils in the abdominal aorta of rats was routinely detected by blood;the morphological changes of lung tissue were observed by HE staining;Masson staining was used to evaluate the fibrosis of lung tissue in rats.;the expression of fibroblasts in lung tissue was detected by immunohistochemical staining;the content of corticosterone and TGF-?1 in serum was detected by ELISA.All data were processed using SPSS 22.0.The normal distribution of measurement data was represented by sx ?.The comparison between groups was analyzed by one-way analysis of variance.P<0.05 was considered statistically significant.Results: There was no significant difference in lung weight-to-weight ratio(lung weight/body weight)between the groups;the ratio of neutrophils in the lipopolysaccharide group and the mifepristone group was significantly higher than that in the normal control group,while there was no significant difference between the rats in the lipopolysaccharide group and the mifepristone group.The difference between the groups was statistically significant(P<0.05).Under the light microscope,the lung tissue of the normal control group was clear and no obvious damage.The pulmonary interstitial thickening in the lipopolysaccharide group and the mifepristone group was accompanied by Inflammatory cells infiltrated;compared with the normal control group,the lung tissue fibroblasts proliferated in the lipopolysaccharide group and the mifepristone group,and the mifepristone group was more proliferative than the lipopolysaccharide group.The difference between the groups was statistically significant(P<0.05).The collagen fibrosis in the lung tissue of the lipopolysaccharide group and the mifepristone group was significantly higher than that of the normal control group,and the lung fibrosis in the mifepristone group was significantly higher than that in the lipopolysaccharide group in the lipopolysaccharide group and the mifepristone group.The difference between the groups was statistically significant(P<0.05).The expression of corticosterone in the serum of the control group was significantly higher than that of the lipopolysaccharide group and the mifepristone group,followed by the mifepristone group,and the lipopolysaccharide group had the lowest expression of corticosterone.The difference between the groups was statistically significant(P<0.05).The expression of TGF-? in the serum of the lipopolysaccharide group and the mifepristone group was significantly higher than that of the normal group,and the mifepristone group was higher than the lipopolysaccharide group.The difference between the groups was statistically significant(P<0.05).Conclusions: Mifepristone may promote the development of inflammation and fibroblast proliferation as well as the expression of some cytokines that promote fibrosis by blocking the glucocorticoid receptor.This effect may promotes the development of pulmonary fibrosis.