A New Style of Dimethylnitrosamine Induced Fulminant Hepatitis in Mice

BACKGROUND: There is still no suitable mice model that can completely mimic the human fulminant hepatitis, which sets a block for drug effect evaluation and mechanism researching of human fulminant hepatitis. OBJECTIVES: The aim of this study was to establish an animal model able to mimic the main features of human fulminant hepatitis. MATERIALS AND METHODS: Dimethylnitrosamine (DMN) was peritoneally injected to mice for liver injury induction. Serum biochemicals, and Prothrombin Time were tested, and Prothrombin activity was calculated, the liver tissue pathological changes were evaluated via macroscopic view observation, HE staining, immunochemical staining, and electron microscopy observation. The mRNA levels of TNF-a, Fas, and IL-1beta were tested with quantitative PCR assay. RESULTS: The serum levels of both ALT and AST were elevated significantly and showed a high plateau. Liver pathological changes were progressed before 48 hours post DMN injection and then started to restore. The mRNA and protein expression levels of TNF-α and IL-1β were significantly elevated. The PT started to extend from 36 hours and PTA was lower than 40% from then on. CONCLUSIONS: This kind of DMN induced mice liver injury is similar to human fulminant hepatitis in main features. This work provided a mice model which could mimic human fulminant hepatitis, and could be valuable for fulminant hepatitis mechanism research and liver protection drug evaluation.