Efficacy and mechanism of ulinastatin on acute lung injury induced by blast in rabbits

Abstract：Objective:To study the effect and mechanism of different doses of ulinastatin (UTI) on acute lung injury(ALI) induced by blast in rabbits.Methods:The models of acute lung injury induced by blast were made in rabbits.All the rabbits were randomly divided into 5 groups:normal group (N group),model group (ALI group),and UTI groups of different doses (L/M/H group),with 8 rabbits in each group.When the model was established,the rabbits in groups L/M/H were intravenously injected with different doses of UTI (2.5,5,10 × 104 U· kg-1),and the rabbits in group N and group ALI were injected with normal saline of the same volume.Bronchial alveolar lavage fluid (BALF),blood,and some lung tissue samples were taken at 24 h.TNF-α and IL-6 were determined by ELISA method.MMP-9 was evaluated by Western blotting and reverse transcription polymerase chain reaction.The wet to dry weight ratios were determined.The pathological changes of lung were observed under microscope.Results:The wet to dry lung weight ratios and the levels of TNF-α,IL-6,MMP-9 in group ALI were significantly higher than those in group N (P ＜ 0.05).The wet to dry weight ratios and the levels of TNF-α and IL-6 in groups L/M/H were lower than those in group ALI,and group H had the most significant difference (P ＜ 0.05).Histopathology examination of lung tissue showed that pulmonary edema and inflammatory in groups M/H were significantly relieved than those in group ALI.Conclusion:UTI could relive inflammation in the lungs of rabbits caused by ALI induced by blast through reducing excessive release of MMP-9 and inflammatory mediators.UTI can be a potential drug for treatment of ALI.