关键词: 乌司他丁, 急性肺损伤, 肿瘤坏死因子, 白细胞介素, p38 MAPK

Abstract: 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 5mg/kg, iv), and intervention group (UTI 50000U/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 3h in rats of model group is 78.55±18.99,128.74±34.79和12.29±1.32 folds against control group, which decreased to 20.95±1.45（p<0.01）,58.15±11.01（p<0.01）和2.85±0.57（p<0.05）folds in intervention group. Expression of IL-10 mRNA at 0.5,1 and 3h in rats of model group is 20.89±4.60,38.20±8.26和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）和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 could attenuate ALI by regulating the gene expression of cytokines. P38 MAPK played role in the decreasing of TNF-alpha mRNA by UTI.

Key words: Ulinastatin, Acute lung injury, Tumor necrosis factor, Interleukin, P38 mitogen-activated protein kinase