Protective Effect of Nicotinamide on Acute Hepatic Failure in Mice / 胃肠病学

ABSTRACT

Background:Acute hepatic failure( AHF)is a common pathophysiological process of end-stage liver disease with complex etiology,difficulty in diagnosis and high mortality rate. Aims:To investigate the protective effect of nicotinamide on AHF in mice. Methods:AHF model in mice was established by intraperitoneal injection with D-galactosamine 700 mg/kg and lipopolysaccharide 10 μg/kg. Fifty-four mice were divided into blank control group,nicotinamide control group, AHF model group and low,moderate,high dose(400,800,1 000 mg/kg)nicotinamide groups,levels of ALT,AST, TNF-α and IL-6 were determined,HE staining was used to examine hepatic histological injury,liver cell apoptosis was measured by TUNEL assay,and protein expression of Caspase-3 was detected by Western blotting. Another 40 mice were divided into AHF model group,saline group and low,moderate,high dose(400,800,1 000 mg/kg)nicotinamide groups,mortality rate was observed dynamically. Results:Compared with blank control group and nicotinamide control group,levels of ALT and AST were significantly increased(P<0. 05),infiltration of inflammatory cells and necrosis of cells and levels of TNF-α and IL-6 were significantly increased( P <0. 05 ),and apoptosis of liver cells and protein expression of Caspase-3 were significantly increased in AHF model group(P <0. 05). In groups pretreated with low, moderate and high dose nicotinamide,all the above-mentioned indices were significantly improved in a dose-dependent manner(P<0. 05). Survival rate in low,moderate,high dose nicotinamide groups was significantly higher than that in AHF model group(37. 5%,62. 5%,100% vs. 0%,P all <0. 05). Conclusions:Nicotinamide could protect mice from AHF via inhibiting inflammatory response and hepatocyte apoptosis,thereby increase the survival rate.