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

ABSTRACT

<p><b>AIM</b>To study the protective action of ulinastatin against lipopolysaccharide (LPS)-induced acute lung injury in mice and the mechanism of its action.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Ulinastatin protected mice from acute lung injury induced by lipopolysaccharides via inhibiting the activation of c-Jun and iNOS mRNA expression.</p>