Cytokines,glucocorticoid receptor mRNA and discrepancy of efficacy of steroid in rat acute lung injury models induced by two different risk factors

Abstract

Objective To explore the inflammatory mechanism,curative efficacy of glucocorticoids in acute lung injury(AM) models induced by lipopolysaccharide(LPS) one hit and LPS-hydrochloric acid(HCl) two hit and potential mechanism. Methods Forty-eight male SD rats were divided randomly into six groups:NS group,LPS group,LPS-HCl group,NS+Dex group,LPS+Dex group, LPS-HCl+Dex group. The total leukocytes and protein content in BALF, W/D, the histological grade, the level of GRmRNA and the concentrations of TNF-α, IL-1β, IL-4 and IL-10 in serum and BALF in every group were measured. Results In LPS+Dex group,the total leukocytes, protein concentration in BALF and W/D were lower than those in LPS group(all P＜0.05). Compared with LPS-HCl group,only W/D in LPS-HCl+Dex group was decreased the corresponding model groups(all P＜0.01 ). Compared with LPS+Dex group, the grade of LPS-HCl+undetected. In LPS-HCl group, the concentration of IL-1β, IL-4 in BALF were higher than those of LPS group (all P＜0.05 ). In LPS + Dex and LPS- HCl+Dex groups, the concentration of TNF- α in BALF and serum was decreased(all P＜0.01) and the concentration of IL-10 in BALF and serum was increased(all P＜0.05). In LPS +Dex group,the concentration of IL-1β in BALF was lower than that in LPS group( P＜corresponding model groups(all P＜0.05), while the parameter in NS+Dex group was lower than that in NS group( P＜0.01). Conclusions The content of cytokines and the permeability in one hit and two hit ALI/ARDS models are not consistent. It suggests that inflammation mechanism of ALI/ARDS is related to different risk factors. GCs can alleviate the pulmonary injury in two model groups, but the efficacy on LPS group is better than LPS-HCl group. It may be related to the number and function situation of GR and the differences in pathogenesis of two model groups. Key words: Acute lung injury, Cytokines; Glucocorticoid receptor mRNA; Hydrochloric acid; Lipopolysaccharide