Protective mechanisms of ulinastatin and dexamethasone against acute lung injury induced by lipopolysaccharide endotoxin in rats

Abstract

Objective To investigate the protective mechanisms of ulinastatin (UTI) and dexamethasone (DXM) against acute lung injury (ALI) induced by lipopolysaccharide (LPS) endotoxin in rats.Methods Twenty four male Sprague-Dawley rats were randomly divided into four groups with 6 mice each group:control group (Con group),LPS group,LPS plus ulinastatin group (UTI group),LPS plus dexamethasone group (DXM group).Rats were killed at 8 h time points,and the protein and mRNA expression levels of glucocorticoid receptor (GR) in the lungs were detected by Western blot and Real Time fluorescent quantitative PCR.The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-10 were also tested by enzyme linked immunosorbent assay (ELISA) and at the same time we tested the lung wet/dry weight radio(W/D).The pathological changes in lung tissue were evaluated by HE staining.Results ① The protein expression levels of GR:LPS group (0.418±0.018) was significantly lower than that in control group (0.841±0.021)(P＜0.05).The protein expression levels of GR in UTI group (0.692±0.018) and DXM group (0.702± 0.024)were higher than that in LPS group (P＜0.05).No significant differences were found between UTI and DXM group in the protein expression levels of GR (P＞0.05).② The expression levels of GRmRNA:LPS group was significantly lower,but the expression level of GRmRNA in UTI group was slightly higher than that in LPS group.No significant differences were found between UTI and LPS group in the expression levels of GRmRNA (P＞0.05),but the expression level of GRmRNA in DXM group was significantly higher than that in UTI group,LPS group and Con group(P＜0.05).③ The expression level of TNF-α:LPS group(374±8) ng/L was significantly higher than that in control group (102±6) ng/L(P＜0.05),the expression level of TNF-α in UTI group(343± 6) ng/L and DXM group(282±8) ng/L fell in between control group and LPS group,but the expression level of TNF-α in DXM group were lower than that in UTI group and higher than those in LPS group,Con group (P＜0.05).④ The expression levels of IL-10:LPS group (264±10) ng/L was significantly higher than that in control group (43±3) ng/L (P＜0.05).In UTI group (369±10) ng/L,the expression level of IL-10 was higher than that in LPS group(P＜0.05).The expression level of IL-10 in DXM group (180±7) ng/L fell in between control group and LPS group (P＜0.05).⑤ The lung W/D:LPS group (5.58±0.28) was significantly higher than that in control group(4.33±0.27)(P＜0.05),the lung W/D in UTI group (5.15±0.18) and DXM group (4.79±0.21) fell in between control group and LPS group (P＜0.05),but the lung W/D in DXM group were lower than that in UTI group (P＜0.05).⑥ Histopathologic examination of lungs:destroyed lung structure,inflammatory cells infiltration,widened alveolar septum with bleeding and edema were seen in LPS group.However,pathological changes in UTI group were milder than those in LPS group and pathological changes in group DXM milder than those in UTI group.Conclusions The protective mechanisms of UTI and DXM against ALI induced by LPS endotoxin in rats are not the same.The protective effect of DXM against ALI is better than UTI. Key words: Acute lung injury; Glucocorticoid receptor; Lipopolysaccharide; Ulinastatin; Dexamethasone