An approach for building a model of acute on chronic liver failure in rat

Objective To explore an approach for building a model of acute on chronic liver failure(ACLF)in rat. Methods Forty SD rats were randomly divided into normal control group,model group 1,model group 2 and model group 3,10 rats for each group.Intraperitoneal injection(ip)for 40%carbon tetrachloride(CCl4)1 mL·kg-1 was performed for rats in group 1,2 and 3 at the 2nd and 5th days every week totally for 4 weeks,respectively.Additional ip for porcine serum0.5 mL or 0.3 mL was performed for rats in group2 or 3 at the 3rd day every week totally for 4 weeks,respectively. All rats in model groups drank5%ethanol freely instead of water.Not any drug injection was performed for rats in normal control group.At the 29th day,lipopolysaccharide(LPS)30μg·kg-1 plus D-galactosamine(D-Gal)0.3 g·kg-1 ip were performed in all rats.Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST)and total bilirubin(TBI) level were detected by the automatic biochemical analyzer.Preparation of liver tissue sections,HE staining and pathological changes were observed by microscope.Results(1)After 4 weeks drug administration,serum ALT,AST and TBil levels of rats in group 1,2 and 3 were significantly higher than those in control group(P0.01),difference among 3 groups was statistically significant(P0.01).(2)Three rats in group 3 died 24 hours after the injection of LPS plus D-Gal.Serum ALT,AST and TBil levels in group 1,2 and 3 were significantly increased compared to before injection(P0.01),and there was statistically significant difference between any two groups(P0.01).(3)Serum ALT,AST and TBIL levels in group 1,2 and 3 decreased 72 hours after injection of LPS plus D-Gal,however,the decreased value was still significantly higher than that of control group(P0.01).(4)It was observed that hepatic sinusoidal dilatation,hyperemia,inflammatory cell infiltration in the portal area,necrosis of hepatocytes in hepatic lobule intact fibrosis septa.Conclusion An animal model of ACLF was built by treating rats with 40% CCl4 plus pig serum albumin and later with LPS of 30μg·kg-1 plus D-Gal 0.3 g·kg-1,which is a potential and novel model for the study of ACLF.