BACKGROUND: Acute liver failure(ALF) is a serious clinical syndrome with high mortality. Sodium butyrate has been shown to alleviate organ injury in a wide variety of preclinical models of critical diseases. The aim o...BACKGROUND: Acute liver failure(ALF) is a serious clinical syndrome with high mortality. Sodium butyrate has been shown to alleviate organ injury in a wide variety of preclinical models of critical diseases. The aim of this study was to investigate the protective effect of sodium butyrate on ALF in rats.METHODS: All rats were randomly divided into control,model and sodium butyrate treatment groups. Except the control group, the rats were induced ALF animal model by subcutaneous injection of human serum albumin+D- galactosamine+lipopolysaccharide. After induction of ALF,the rats in the treatment group received sodium butyrate(500mg/kg) at 12-hour or 24-hour time point. Fourty-eight hours after ALF induction, the animals were sacrificed and samples were harvested. Serum endotoxin, high mobility group box-1(HMGB1), liver function parameters, tumor necrosis factoralpha(TNF-α) and interferon-gamma(IFN-γ) were measured.The expression of HMGB1 and nuclear factor-kappa B(NF-κB)p65 protein in liver tissue was detected by Western blotting. The histological changes of liver and intestine were examined. The survival duration was also observed.RESULTS: Serum endotoxin, alanine aminotransferase, HMGB1,TNF-α and IFN-γ were significantly increased and the liver histology showed more severe histopathological injury in the model group compared with the control group(P<0.05).Compared to the model group, sodium butyrate treatment significantly improved the histopathological changes in the liver and intestine, reduced serum endotoxin and inflammatory cytokines, suppressed HMGB1 and NF-кB p65 proteins in liver tissue, and prolonged the survival duration regardless of treatment at 12 hours or 24 hours after induction of ALF(P<0.05).CONCLUSIONS: Sodium butyrate protected the liver from toxin-induced ALF in rats. The mechanisms may be due to direct hepatoprotection and decreased intestinal permeability.展开更多
基金supported by a grant from the National Natural Science Foundation of China(81071342)
文摘BACKGROUND: Acute liver failure(ALF) is a serious clinical syndrome with high mortality. Sodium butyrate has been shown to alleviate organ injury in a wide variety of preclinical models of critical diseases. The aim of this study was to investigate the protective effect of sodium butyrate on ALF in rats.METHODS: All rats were randomly divided into control,model and sodium butyrate treatment groups. Except the control group, the rats were induced ALF animal model by subcutaneous injection of human serum albumin+D- galactosamine+lipopolysaccharide. After induction of ALF,the rats in the treatment group received sodium butyrate(500mg/kg) at 12-hour or 24-hour time point. Fourty-eight hours after ALF induction, the animals were sacrificed and samples were harvested. Serum endotoxin, high mobility group box-1(HMGB1), liver function parameters, tumor necrosis factoralpha(TNF-α) and interferon-gamma(IFN-γ) were measured.The expression of HMGB1 and nuclear factor-kappa B(NF-κB)p65 protein in liver tissue was detected by Western blotting. The histological changes of liver and intestine were examined. The survival duration was also observed.RESULTS: Serum endotoxin, alanine aminotransferase, HMGB1,TNF-α and IFN-γ were significantly increased and the liver histology showed more severe histopathological injury in the model group compared with the control group(P<0.05).Compared to the model group, sodium butyrate treatment significantly improved the histopathological changes in the liver and intestine, reduced serum endotoxin and inflammatory cytokines, suppressed HMGB1 and NF-кB p65 proteins in liver tissue, and prolonged the survival duration regardless of treatment at 12 hours or 24 hours after induction of ALF(P<0.05).CONCLUSIONS: Sodium butyrate protected the liver from toxin-induced ALF in rats. The mechanisms may be due to direct hepatoprotection and decreased intestinal permeability.
