Abstract: Objective To establish an ideal model of chronic liver injury and evaluate stability of the modeling methods. Methods In this study, the mouse model of non-alcoholic steatohepatitis (NASH), the mouse model of liver fibrosis and the rat model of cirrhosis were induced by the modified high-fat diet (HFD), carbon tetrachloride (CCl4) and thioacetamide (TAA), respectively. Pathological hematoxylin-eosin (HE), oil red O and sirius red (SR) staining were used to observe the structural changes, steatosis and fibrosis of animal liver. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), γ-glutamyltransferase (GGT),glycyl proline dipeptidyl aminopeptidase (GPDA), albumin (ALB), total cholesterol (TC) and triglyceride (TG) were detected by automatic biochemical instrument. Results Compared with traditional diet group (8 mice), the modified HFD group (64 mice) could increase the activities of ALT [(268.7 ± 69.8) vs (35.0 ± 21.9)], AST [(215.0 ± 91.0) vs (34.4 ± 9.4)] and LDH [(560.3 ± 158.5) vs (240.6 ± 101.3)] significantly (all P<0.05), and decrease the activities of TC [(1.5 ± 0.3) vs (2.2 ± 0.2)] and TG [(0.9 ± 0.1) vs (1.6 ± 0.2)] significantly (both P<0.05). In the pathological results, oil red O and HE staining were observed in pathology showed that the hepatic tissue of mice fed with the modified HFD were filled with lipid droplets. Compared with mice injected with olive oil (8 mice), levels of ALT [(8507.3 ± 1083.1) vs (41.8± 29.2)] and AST [(4911.2 ± 644.0) vs (104.0 ± 33.6)] increased significantly (P<0.05) in mice injected with 10% CCl4 (2mL/kg, tiw) for 12 weeks (52 mice). The pathological results of HE and SR staining showed that there was a large number of collagen fibers in the liver tissue of mice injected with CCl4. Compared with mice injected with normal saline (8 rats), levels of ALT [(197.3 ± 131.1) vs (34.0 ± 6.0)], AST [(590.3 ± 457.7) vs (57.5 ± 12.3)], GGT [(10.0 ± 8.4) vs (3.6 ± 3.3)] and GPDA [(290.5 ± 134.4) vs (63.3 ± 14.7)] increased significantly (all P<0.05) and level of ALB [(37.3 ± 1.9) vs (40.9 ± 1.3)] decreased significantly (P<0.05) in rat injected with TAA (200mg/kg, biw) for 16 weeks (37 rats). The pathological analysis of HE and SR staining showed that the liver tissue of rats injected with TAA presented with hepatic fibrosis, proliferation of hepatic fibroblasts and formed pseudo lobules with different sizes. Conclusion Mice were fed with the modified HFD for 2 weeks, the success rate of NASH model was 100%. The model was further aggravated after feeding for 4 weeks. In terms of mice that were injected with 10% CCl4 (2 mL/kg, tiw) for 12 weeks, the success rate of liver fibrosis model was 100%, and the model could be maintained for at least 2 weeks after drug withdrawal. Rats were injected with TAA (200mg/kg, biw) for 16 weeks, the success rate of liver cirrhosis model was 100%, and the model could last for at least 4 weeks after drug withdrawal.

Key words: Chronic liver disease, Animal models, Non-alcoholic steatohepatitis, Liver fibrosis, Cirrhosis