Effects of high mobility group box-1 protein on hepatic dysfunction during murine acute necrotizing pancreatiyis / 中华急诊医学杂志

ABSTRACT

Objective To explore the effects of ethyl pyruvate (EP) on hepatic high mobility group box-1 protein (HMGB1) expression in experimental routine with acute necrotizing pancreatitis (ANT). Method ANP model was induced by retrograde injection of 5 % sodium taurocholate into pancreatic duct. Twenty-four male wistar rats were divided randomly into 3 groups(8 rats in each group) group A (ANT group); group B (ANP rats re-ceived ethyl pyruvate therapy) and group C (control group with sham operation). The concentration of plasma amylase (AMY), A.sr and ALT, and the activity of myeloperoxidase (MPO) in the liver were determined. The ex-pression of HMGB1 mRNA in liver was detected by using reverse transcription polymerase chain reaction (RT-PCR). The changes of morphological damage were observed under microscopy. The expression of HMGB1 in the liver was observed by using SP immunohistochemistry. ANOVA was performed with SPSS 10.0 statistical analysis software and the difference was accepted as significant if the P<0.05, as verified by using Duncan's and Tukey' s post hoc test. Results Compared with gxoup A,levels of plasma AMY,AST and ALT in group B were markedly lower (P<0.05). Compared with group C, MPO in group A was higher significantly (P<0.01).with group A, the pathological changes of pancreas and liver in group B were milder. Compared with group C,the hepatic HMGB1 mRNA expression was markedly higher in group A [(0.28±0.04) vs. (0.73±0.06), P<0.01]. By contrast,the HMGB1 mRNA expression was markedly lower in group B compared with group A [(0.46±0.05) vs. (0.73±0.06), P<0.05]. The HMGB1 protein expression in hepatocytes and Kupffer's cells of rats with ANP was significantly up-regulated compared with control group, but it was reduced significantly in EP treatment group. Conclusions HMGB1 as a late mediator in liver might be involved in the pathogenesis of acute hepatic injury with ANP. EP could down-regulate the hepatic HMGB1 expression together with improvement of liver function in rats with ANP.