Evaluation on three short-term animal models of alcoholic liver disease

Alcoholic liver disease (ALD) includes a spectrum of disorders ranging from asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis and cirrhosis. According to epidemical statistics, ALD has been ranked as the second major cause of liver diseases in China. Many animal models have been made in the study of potential therapies. However, in most of the models, the pathological changes are not always consistent with those in patients. There are three widely used short-term animal models of ALD:the acute alcoholic liver injury model, Gao-binge steatohepatitis model and CCl₄-alcohol diet induced liver fibrosis model. In this study, we evaluated the pathological responses of these models and compared the responses with the clinical parameters. The liver/body weight ratio was increased and liver histological lesions were induced in alcoholic groups in the three models, while the levels of biochemical parameters and inflammatory factors were affected by different type of treatments. In the acute alcoholic model, the mRNA levels of interleukin-6 (IL-6) and C-C motif chemokine receptor-2 (CCL2) were surprisingly decreased, which was consistent with the transcriptome profile in patients (P < 0.05), but the serum ALT and AST level, were not changed. In Gao-binge model, both AST/ALT and triglyceride levels were significantly induced by alcoholic consumption (P < 0.05), along with the gene expression levels of hepatic IL-6 and CCL2 (P < 0.05). These data were similar in tendency to the pathological indicators of hepatitis patients. In liver fibrosis model, although histological section indicated obvious fibrotic lesion and little lipid accumulations, other indexes were barely changed. In conclusion, the Gao-binge model induced similar pathological patterns to those of steatohepatitis patients. Gao-binge model might be ideal for study of ALD, especially alcoholic steatohepatitis. In addition, we also found that hepatic gene expression of CCL2 was impacted differently at various stages of ALDs, which can be considered as a potential biomarker.