Role of glucocorticoid receptor in acute lung injury induced by lipopolysaccharide in rats

Objective To evaluate the role of glucocorticoid receptor (GR) in acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats.Methods Sixty male Sprague-Dawley rats,weighing 180-230 g,were randomly divided into 4 groups:control group (group C,n =6) ; GR specific inhibitor RU486 group (group R,n =6) ; ALI group (n =24) ; RU486 + ALI group (group RA,n =24).ALI was induced by injection of LPS 5 mg/kg via the tail vein in groups ALI and RA,while the equal volume of normal saline was given in group C and RU486 20 mg/kg was injected subcutaneously in group R.RU486 20 mg/kg was injected subcutaneously 90 min before LPS administration in group RA.Eight rats were chosen at 1,3,and 6 h after LPS administration (T11-3) in groups ALI and RA and at 1 h after normal saline or RU486 administration in groups C and R and sacrificed.The lungs were removed for determination of the expression of phosphorylated p38 mitogen-activated protein kinase (pp38MAPK) and mitogen-activated protein kinase phosphatase-1 (MKP-1) in lung tissues.The concentrations of albumin and TNF-α in bronchoalveolar lavage fluids (BALF) were detected,histopathological changes in lung tissues were observed and apoptosis index (AI) was calculated at T3.Another 32 Sprague-Dawley rats,weighing 180-230 g,were randomly divided into 2 groups (n =16 each):group ALI1 and group RA1.The rats were treated as the method mentioned above and observed for the 48 h survival rate.Results Compared with group C,the concentrations of protein and TNF-α in BALF and AI were significantly increased,the histopathological damage was aggravated,and p-p38MAKP expression was up-regulated at T1-3 in groups ALI and RA,and MKP-1 expression was downregulated at T2,3 in group ALI and at Ti-3 in group RA (P ＜ 0.05).Compared with group ALI,the concentrations of protein and TNF-α in BALF and AI were significantly increased,p-p38MAKP expression was up-regulated at T1-3 (P ＜ 0.05),and no significant change was found in MKP-1 expression at T2,3 in group RA (P ＞ 0.05).The 48 h survival rate was significantly lower in group RA1 than in group ALI1 (P ＜ 0.05).Conclusion Glucocorticoid receptors are involved in the development of LPS-induced ALI,and the mechanism may be related to the inhibition of p38MAPK signal transduction pathways and decrease in cell apoptosis in rat lung tissues. Key words: Receptors, glucocorticoid;  Respiratory distress syndrome, adult;  Endotoxins;  p38 mitogen-activated protein kinases;  Lung