乌司他丁对脂多糖致小鼠急性肺损伤的保护作用以及与诱导型一氧化氮合酶和c-Jun表达的关系

目的探讨乌司他丁对脂多糖(LPS)致小鼠急性肺损伤的作用及其机制。方法小鼠腹腔注射乌司他丁(50和100 ku·kg^-1)或等体积生理盐水30 min后，分别静脉注射LPS 15 mg·kg^-1或等体积生理盐水，于注射LPS后不同时间检测有关各项指标。ELISA法测定血清和肺组织中TNFα水平，RT-PCR法测定TNFα mRNA和iNOS mRNA的表达。Western blotting法检测c-Fos，c-Jun及iNOS等蛋白表达。结果乌司他丁100 ku·kg^-1能显著降低LPS引起的小鼠的肺脏指数、肺组织及血清中NO水平的增加，下调肺组织c-Jun蛋白表达量和iNOS mRNA及其蛋白的表达量，而对小鼠的血清和肺组织冲洗液中TNFα含量以及肺组织MDA无明显影响。结论乌司他丁对LPS引起的小鼠肺损伤有保护作用，该作用与其抑制c-Jun蛋白和iNOS mRNA的表达有关。

Protective action of ulinastatin against lipopolysaccharides-induced acute lung injury in mice and the relation of it to iNOS and c-Jun expressions

AIM: To study the protective action of ulinastatin against lipopolysaccharide (LPS)-induced acute lung injury in mice and the mechanism of its action. METHODS: Mice were intraperitoneally injected with ulinastatin (50 and 100 ku x kg(-1)) or saline at a period of 12 h, separately, 30 min after the last injection of ulinastatin, except normal control, all mice of other groups were injected a dose of LPS 15 mg x kg(-1) via tail vein. The levels of TNFalpha in serum and lung were measured by ELISA. The expression of TNFalpha mRNA and iNOS mRNA in lung was assayed by RT-PCR. The expression of c-Fos and c-Jun protein in lung was measured by Western blotting method. And the NO2- / NO3- level in serum and MDA in lung were measured with kits. RESULTS: The levels of NO2- / NO3- and TNFalpha in serum, MDA and TNFa in lung all increased after iv injection of LPS. The expressions of TNFa mRNA, iNOS mRNA, c-Fos and c-Jun in lung of LPS-injected mice were enhanced. Pretreatment with ulinastatin 100 ku x kg(-1) decreased the levels of NO2- / NO3- in serum and lung, reduced the index of lung, and inhibited the expressions of iNOS mRNA and c-Jun in lung induced by LPS in mice, while ulinastatin showed no effect on TNFa level in serum and lung. CONCLUSION: Ulinastatin protected mice from acute lung injury induced by lipopolysaccharides via inhibiting the activation of c-Jun and iNOS mRNA expression.