Effect of dexamethasone on MKP-1 expression in lung tissues in rats with lipopolysaccharide-induced acute lung injury

Abstract

Objective To investigate the effect of dexamethasone on mitogen-activated protein kinase phosphatase-1 (MKP-1) expression in lung tissues in rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI).Methods Fifty-four male SD rats weighing 180-230 g were randomly divided into 3 groups:control group (group C,n =6) ;ALI group ( n =24) and dexamethasone group (group D,n =24).LPS 5 mg/kg was injected via tail vein in groups ALI and D,while the equal volume of normal saline was given in group C.Dexamethasone 6 mg/kg was injected intraperitoneally at 30 min before LPS administration in group D.Eight rats in each group were sacrificed at 1 h after normal saline administration (T1) in group C and at 1,3,and 6 h after LPS administration (T1-3 ) in groups ALI and D.The lung tissues were then removed for determination of the expression of phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK) and MKP-1.The concentrations of albumin and TNF-α in bronchoalveolar lavage fluid (BALF) were detected and histopathological changes were observed at T3 ·Another 32 SD rats weighing 180-230 g were randomly divided into 2 groups ( n =16 each):group ALI1 and group D1.The rats were treated as the method mentioned above and the 48 h survival condition was observed.Results Compared with group C, the concentrations of protein and TNF-α in BALF were significantly increased,p-p38MAKP expression was up-regulated at T1.3,and MKP-1 expression was down-regulated at T2,3 in group ALI,and TNF-α concentration in BALF was significantly increased and the expression of p-p38MAKP and MKP-1 was up-regulated at T1-3 in group D ( P ＜ 0.05).Compared with group ALI,the concentrations of protein and TNF-α in BALF were significantly decreased,p-p38MAKP expression was down-regulated and MKP-1 expression was up-reg-ulated at T1-3 ( P ＜ 0.05 ),and the pathological damage was attenuated in group D.The 48 h survival rate was significantly higher in group D1 than in group ALI1 ( P ＜ 0.05).Conclusion The mechanism by which dexamethasone attenuates the ALI induced by LPS may be related to up-regulation of MKP-1,inhibition of phosphorylation of p38MAPK and decrease in inflammatory response. Key words: Dexamethasone; Respiratory distress syndrome, adult; Endotoxins; Mitogen-activated protein kinase phosphatase -1; Lung