Abstract: Objective · To construct a non-alcoholic steatohepatitis (NASH) mouse model by the combination of Western diet (WD) and low-dose carbon tetrachloride (CCl4), and explore the time nodes of typical NASH pathological changes. Methods · Male 8-week C57BL/6 mice were fed WD and intraperitoneally injected with CCl4 at a dose of 2 μL/g of body weight per week to construct NASH models. At different time points, the fasting blood glucose, and the levels of triacylglyceride, glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase were tested; glucose tolerance was tested at the 24th week. Besides, the liver index was calculated and oil red O staining, Sirius red staining, hematoxylin-eosin staining and TUNEL test were conducted to evaluate liver pathological changes after liver sampling. Results · Between the control group and model group, there was no significant difference in fasting blood glucose and glucose tolerance test result, while the significant differences of liver index were observed at the 8th, 12th and 24th week (P<0.05). And at the 24th week, the levels of triacylglyceride, glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase were higher in the model group than those in the control group (P<0.05). According to the results of oil red O staining, Sirius red staining, hematoxylin-eosin staining and TUNEL test, in the model group, a large amount of small lipid droplets accumulation in the liver tissues was detected and hepatocytes were mainly in apoptotic state at the 8th week; large lipid droplets, hepatocellular ballooning and spot-like necrosis were observed, and hepatocyte apoptosis persisted at the 16th week; stage 3 fibrosis of liver was observed, and the number of spot-like necrosis increased but lipid droplets decreased, while hepatocytes were mainly in a proliferative state at the 24th week. Conclusion · The mouse model of NASH can be established successfully by WD combined with low-dose CCl4, which can simulate the pathologic features of NASH in a short time.

Key words: animal model, non-alcoholic steatohepatitis (NASH), Western diet (WD), carbon tetrachloride (CCl4)