Effects of ulinastatin on NF-κB expression in lung tissue of rats with acute lung injury

Objective To study the mechanism of protective effect of ulinastatin(UTI) on lung with LPS-induced acute lung injury(ALI) in rats.Methods Thirty-six male SD rats were randomly divided into three groups: normal control group(NC),lipopolysaccharide injury group(LPS) and UTI treatment group(UTI).ALI model of rats was reproduced with LPS.Rats in LPS group and UTI group received injection of LPS 5mg/kg via femoral vein,and then the rats in UTI group received injection of UTI 50 000U/kg.Rats in NC group received an injection of 2ml 0.9% NaCl.PaO2 was detected for all the three groups 2h and 4h after injection.Half of rats in each group were then sacrificed by exsanguination,and lungs were harvested for the assessment of lung wet/dry weight ratio(W/D),MPO activity and MDA level.The pathological changes in lung tissues were examined with HE-stained lung sections.TNF-α protein was measured by ELISA,and the expression of NF-κB was examined by immunohistochemistry.Results The W/D ratio of lung tissue was significantly increased in the rats of LPS and UTI group compared with that of NC group(P0.05),while no significant difference existed between LPS and UTI groups(P0.05).PaO2 decreased significantly in LPS group at 2h and 4h time points after injection compared with that in NC group(P0.01).PaO2 was higher in UTI group at each time point compared with that in LPS group(P0.05),while lower than that in NC group(P0.05).No significant difference in PaCO2 was found between UTI and LPS groups(P0.05).Marked histological damage was found in the lungs of rats of LPS group characterized by destruction of lobules,neutrophil infiltration and hemorrhage in alveolar spaces.Similar changes were also found but in a mild degree in the rats of UTI group.MPO activity and MDA level were significantly higher in LPS group than that in NC and UTI group(P0.05).The expressions of NF-κB and TNF-α were down regulated in UTI group compared with those in LPS group at the same time points(P0.05).Conclusion In LPS-induced acute lung injury,early administration of UTI could inhibit the activation of neutrophils and NF-κB,down-regulate the production of TNF-α,and play a protective effect on lung.