Abstract: Objective · To establish a reliable alcoholic liver disease mouse model (ALDNM) that mimics the drinking pattern of alcoholic liver disease (ALD) patients.  Methods · Using the self-designed feeding tubes and liquid diet, ALDNM model was developed through chronic feeding combined with acute gavage of ethanol based on Lieber-DeCarli model and Gao-Binge model. C57BL/6 mice were administered with control liquid diet for adaptation for first 5 d, and then divided into pair-fed group and ethanol-fed group (10 mice each group). Ethanol-fed mice were fed with the liquid diet in which ethanol accounts for 30% of total energy, while the pair-fed mice were fed with the control diet for 10 d. At the 16th day, ethanol-fed mice and pair-fed mice were respectively gavaged a single dose of 31.5% ethanol or isocaloric maltose dextrin, and euthanized 9 h later. Sera and livers were collected. The general physiological condition, hepatic tissue pathological changes and serum indexes between Lieber-DeCarli models and ALDNM models were compared. The liver lipids of ALDNM mice were determined by Oil red O (ORO) staining and hepatic triacylglyceride (TAG) test. Meanwhile, the mRNA levels of interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), fatty acid synthase (Fas), long chain fatty acid elongase 6 (Elovl6) and stearyl-CoA desaturase (Scd1) were detected by real-time PCR in ALDNM models. Western blotting was used to detect the changes of phosphorylated signal transduction and transcriptional activator (p-STAT3) in the livers.  Results · Lieber-DeCarli model mice were generally in poor condition, and there was no significant change in serum glutamic-pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) compared to pair-fed group. However, in ALDNM models, H-E staining showed that the hepatocytes of ethanol-fed mice were extremely swollen with round volume, increased cytoplasm and filled with large amounts of fat vacuoles. ORO staining analyses showed obvious microsteatosis in the liver cells from all ethanol-fed mice. The hepatosomatic index, liver TAG content, serum GPT and GOT of ALDNM models were significantly higher than those in the pair-fed group, while the serum HDL significantly decreased compared to the pair-fed group. Moreover, the expression levels of both lipid synthesis pathways and inflammatory signaling pathways related genes in livers significantly increased in the ethanol-fed mice of ALDNM model.  Conclusion · ALDNM model was successfully constructed. This model is cost- and time-efficient. Moreover, ALDNM model mimics the drinking pattern and pathogenesis of ALD patients with the advantages of stable food intake, good repeatability, and obvious liver damage.

Key words:  alcoholic liver disease, mouse, animal model, inflammatory signaling pathway, lipid synthesis pathway