The roles of glucocorticoid and glucoorticoid receptor in the pulmonary fibrosis caused by acute lung injury induced by lipopolysaccharide in rats

Objective To investigate the role of glucocorticoid(GC) and glucocorticoid receptor(GR) in the pulmonary fibrosis caused by lipopolysaccharide(LPS)-induced acute lung injury(ALI).Methods Sixty rats were randomly divided into three groups,ie.a control group(n=10),an ALI group(n=30),and a dexamethasone(Dex) treatment group(n=20).ALI was induced by intraperitoneal injection of LPS(5 mg/kg) for 3 days in the ALI and Dex groups.Then the rats in the Dex group were treated with intraperitoneal injection of Dex(5 mg/kg) at 8:00 AM every day from the 4th day on.Ten rats in each group were randomly sacrificed on the 3th,7th and 14th day respectively.Blood analysis,airway resistance and compliance were measured before sacrificed.Histological examination was performed with HE and VP staining.The protein concentration,total and differential cells counts in bronchoalveolar lavage fluid(BALF) and lung wet-dry weight ratio were examined.The levels of hydroxyproline and procollagen aminoterminal propeptide type Ⅰ and Ⅲ(PINP and PIIINP) in lung tissue were measured by digestion method and ELISA respectively.The GR expression in lung tissue was detected by immunohistochemistry.Results The lung resistance of the dexamethasone-treated rats was significantly decreased in comparison with the ALI group on the 7th day[(0.49±0.11)kPa·mL-1·s-1 vs(0.59±0.08)kPa·mL-1·s-1,P0.05] and on the 14th day[(0.59±0.07)kPa·mL-1·s-1 vs(0.68±0.25)kPa·mL-1·s-1,P0.05].PINP in BALF decreased significantly after dexamethasone administration [(74.13±2.27)pg/mL vs(90.73±3.29)pg/mL,P0.01].The dexamethasone-treated animals showed alleviated pulmonary fibrosis compared to the ALI group as shown by histology and hydroxyproline content [(264.41±8.41)mg/g vs(293.80±26.85)mg/g,P0.05].The GR level was significantly increased in the dexamethasone-treated rats in comparison with the ALI group.Conclusions The results suggest that an early treatment with dexamethasone may be useful in inhibiting pulmonary fibrosis of LPS-induced ALI.It is possible that the dexamethasone treatment suppresses lung fibrosis by upregulating the GR expression in lung.