Wu Yi-Jun, Ling Qi, Zhou Xin-Hui, Wang Yan, Xie Hai-Yang, Yu Ji-Ren, Zheng Shu-Sen
Department of General Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Hepatobiliary Pancreat Dis Int. 2009 Feb;8(1):53-8.
Urinary trypsin inhibitor (UTI) inhibits the inflammatory response and protects against ischemia-reperfusion (I/R) injury. The inflammatory response is mediated by nuclear factor-kappa B (NF-kappaB) and its related target genes and products such as vascular endothelial cell adhesion molecule and CXC chemokines. We aimed to assess the roles of those mediators in a UTI-treated mouse model of hepatic I/R injury.
Treatment group 1 (UTI given 5 minutes prior to liver ischemia), treatment group 2 (UTI given 5 minutes after the anhepatic phase) and a control group were investigated. Blood and liver samples were obtained and compared at 1, 3, 6 and 24 hours after reperfusion.
Attenuation of pathological hepatocellular damage was greater in the treatment groups than in the control group (P<0.05). Compared with the control group, the UTI treatment groups showed significantly lower serum alanine aminotransferase and aspartate aminotransferase levels, decreased myeloperoxidase activity, and reduced NF-kappaB activation. Also downregulated was the expression of tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractant, and macrophage inflammatory protein-2 at the mRNA level. P-selectin protein and intercellular adhesion molecule-1 protein expression were also downregulated. In addition, the treatment group 1 showed a better protective effect against I/R injury than the treatment group 2.
UTI reduces NF-kappaB activation and downregulates the expression of its related mediators, followed by the inhibition of neutrophil aggregation and infiltration in hepatic I/R injury. The protective role of UTI is more effective in prevention than in treatment.
尿胰蛋白酶抑制剂（UTI）可抑制炎症反应并预防缺血再灌注（I/R）损伤。炎症反应由核因子-κB（NF-κB）及其相关靶基因和产物介导，如血管内皮细胞黏附分子和CXC趋化因子。我们旨在评估这些介质在UTI治疗的肝I/R损伤小鼠模型中的作用。
研究了治疗组1（肝脏缺血前5分钟给予UTI）、治疗组2（无肝期后5分钟给予UTI）和对照组。在再灌注后1、3、6和24小时采集血液和肝脏样本并进行比较。
治疗组肝细胞病理损伤的减轻程度大于对照组（P<0.05）。与对照组相比，UTI治疗组血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平显著降低，髓过氧化物酶活性降低，NF-κB激活减少。肿瘤坏死因子-α、细胞因子诱导的中性粒细胞趋化因子和巨噬细胞炎性蛋白-2在mRNA水平的表达也下调。P-选择素蛋白和细胞间黏附分子-1蛋白表达也下调。此外，治疗组1对I/R损伤的保护作用优于治疗组2。
UTI可降低NF-κB激活并下调其相关介质的表达，进而抑制肝I/R损伤中中性粒细胞的聚集和浸润。UTI的保护作用在预防方面比治疗方面更有效。
