Objective To explore the protective effect of ulinastatin (UTI) in a rat model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the underlying molecular mechanism.Methods Wistar rats were randomly assigned into: control group, model group (LPS 5 mg/kg, iv ), and intervention group (UTI 50 000 U/kg, iv).Expression of TNF-alpha and IL-10 mRNA in lung tissue were measured by real time RT-PCR.Expression of phosphorylated P38 MAPK in lung tissue were detected by immunohistochemical staining and Western blot methods.Results Expression of TNF-alpha mRNA at 0.5,1 and 3 h in rats of model group is 78.55 ± 18.99,128.74 ± 34.79 and 12.29 ± 1.32 folds against control group, which decreased to 20.95 ± 1.45 ( P ＜ 0.01 ),58.15 ± 11.01 (P ＜0.0l ) and 2.85 ±0.57(P ＜0.05 ) folds in intervention group.Expression of IL-10 mRNA at 0.5,1 and 3 h in rats of model group is 20.89 ±4.60,38.20 ±8.26 and 53.26 ±8.01 folds against control group,which increased to 66.77 ± 11.18 ( P ＜ 0.05 ) ,97.69 ± 27.00 ( P ＜ 0.01 ) and 128.62 ± 42.30 ( P ＜ 0.01 ) folds against invention group.Administration of LPS elevated the expression of P38 MAPK, which were significantly attenuated by UTI at each time point( ( P ＜ 0.05 ).Conclusion UTI may attenuate ALI by regulating the gene expression of eytokines.P38 MAPK played role in the decreasing of TNF-alpha mRNA by UTI.%目的 探讨乌司他丁(UTI)对脂多糖(LPS)诱导急性肺损伤(ALI)大鼠的保护作用及分子生物学机制.方法 Wistar大鼠随机分为对照组、模型组(LPS 5 mg/kg,iv)和干预组(UTI 50 000 U/kg,iv),用Real time RT-PCR法检测肺组织TNF-α和IL-10 mRNA表达,用免疫组化染色和Western blot技术检测肺组织中P38 MAPK的表达.结果 模型组0.5、1和3 h时TNF-α mRNA的表达分别是对照组的78.55±18.99、128.74±34.79和12.29±1.32倍,UTI干预后分别降至20.95±1.45(P<0.01),58.15±11.01(P<0.01)和2.85±0.57(P<0.05)倍.模型组0.5、1和3 h IL-10 mRNA的表达分别是对照组的20.89±4.60,38.20±8.26和53.26±8.01倍,UTI 干预后分别升至66.77±11.18(P<0.05),97.69±27.00(P<0.01)和128.62±42.30(P<0.01)倍.模型组P38 MAPK的表达在各个时点均明显升高,UTI干预后P38 MAPK的表达减弱(P<0.05).结论 UTI通过调节细胞因子基因表达发挥其肺保护作用.P38 MAPK信号通路在UTI下调TNF-αmRNA的表达中发挥了作用.
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