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Urinary trypsin inhibitor attenuates hepatic ischemia-reperfusion injury by reducing nuclear factor-kappa B activation.
Wu, Yi-Jun; Ling, Qi; Zhou, Xin-Hui; Wang, Yan; Xie, Hai-Yang; Yu, Ji-Ren; Zheng, Shu-Sen.
Afiliação
  • Wu YJ; Department of General Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Hepatobiliary Pancreat Dis Int ; 8(1): 53-8, 2009 Feb.
Article em En | MEDLINE | ID: mdl-19208516
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glicoproteínas / Traumatismo por Reperfusão / NF-kappa B / Hepatopatias Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2009 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glicoproteínas / Traumatismo por Reperfusão / NF-kappa B / Hepatopatias Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2009 Tipo de documento: Article