The protection efffcts of glucocorticoid receptor on LPS-induced acute lung injury in rats

Abstract

Objective To examine the role of glucocorticoid receptor(GR) in regulation of lipopolysaccharide(LPS)-induced lung injury. Methods 84 mail Sprague-Dawley rats were randomly divided into five groups: Control group, received an injection of 0.9% sodium chloride; LPS group, received LPS injection(5 mg/kg, intravenously,i.v.);Dex+LPS group, received dexamethasone injection (6 mg/kg, intraperitoneally, i.p.); RU486 group, received glucocorticoid receptor antagonist RU486 injection (20 mg/kg,subcutaneously, s.c.); RU486+Dex+LPS group, received the injections of the three drugs seriatim as mentioned previously. All the animals were killed under anesthesia by intraperitoneal injection of pentobarbital at each time point. The concentration of albumin in bronchoalveolar lavage fluids(BALF), lung index(LI), apoptosis index(AI), the histopathologic changes of lung tissues, activation of p38MAPK and expression in lung tissue were detected. Results BALF protein content(77±9) g/L, LI(5.93±0.44), AI(43.9±3.1 )%significantly increased at 6h after LPS administration than those in Control group (49±5) g/L, 2.36±0.14, (12.0±1.7)%(P＜0.05). Pulmonary H-E stain showed serious pulmonary inflammation and conspicuous lung injury .Compared with the LPS group, the albumin leakage(54±4) g/L, LI(3.77±0.48),AI( 32.7±2.7)%in Dex+LPS group was significantly attenuated with protection of tissue damage (P＜0.05), while all the protective effects of Dex might be cancelled by GR antagonist (RU486). Western blot analysis showed the expression of p-p38MAPK in lung tissues was significantly increased in LPS group than that in Control group (P＜0.05).The expression of p-p38MAPK was down-regulated in Des+LPS group than that in LPS group(P＜0.05),but the expression in RU486+Dex+LPS group was similar to LPS group (P＞0.05). Conclusion GR plays an essential role in regulation of LPS-induced ALI.Anti-apoptosis effects of hormone-activated GR may be mediated by inhibition of p38MAPK phosphorylation/activation. Key words: Glucocorticoid; Receptor; Lipopolysaccharide; p38MAPK; Apoptosis; Acute lung injury