Establishment of carbon tetrachloride-induced liver fibrosis model with incremental dose approach in rabbits

Objective To establish a liver fibrosis model and to explore its dynamic biochemical and morphological changes in rabbits.Methods Thirty-eight male rabbits were randomly divided into a control(n=7)and a model group(n=28).In model group, the rabbits were subcutaneously injected with carbon tetrachloride(CCl₄)using incremental dose approach, i.e.the rabbits were injected with 40% CCl₄ at dose of 0.2 mL/kg for the first two weeks, then the dosage was increased to 0.5, 1.0 and 1.5 mL/kg, respectively, for the the 3rd, 9th and 15th week.The control was adminstrated with equal amount of saline.In the expreiment, the rabbits were continuously injected CCl₄ for 2 weeks(two times a week)with 1 week withdrawal for 20 weeks.The pathology and serum biochemical parameters were detected at the end of 0, 5th, 8th, 11th, 17th, and 20th week, respectively.Results During the experiment, two rabbits in the model group died.With the time of experiment, the hepatocytes presented pathologic changes with fatty liver degeneration, necrosis, fibrous septa formation, lobular structural disorder, and ultimately the formation of false lobules.The fibrosis scores were 1.4±0.54(P<0.05), 1.8±0.45(P<0.05), 2.8±0.45(P<0.01), and 3.57±0.55(P< 0.01), respectively, at 8th, 11th, 17th, and 20th week.Meanwhile, serum alanine aminotransferase and aspartate aminotransferase showed a transient increase, with the peaks of 355.1±311.5 and 840.5±45.8(both P<0.01)at the 8th week, and then gradually decreased.Conclusion Subcutaneous injection of CCl₄ for 20 weeks could be used to establish a stable and ideal liver fibrosis model with low mortality rate in rabbits.