Establishment of a novel rat model of liver transplantation with nonalcoholic fatty liver graft

Objective We try to establish a novel nonalcoholic fatty liver model in rat, which was similar to the steatosis liver in huan, and to investigate the graft function and survival after liver transplantation. Methods Lewis rats, weighting from 40 to 50 g, were chose to establish fatty liver model by high-fat diet feeding. Lewis rats were fed normal rat chow in the control group, high-fat chow in moderate fatty liver (MFL) group for 6 weeks, and high-fat chow in severe fatty liver (SFL) group for 10 weeks respectively. Brown Norway (BN) rats, 8-10 weeks of age and weighing 250-350 g, were used as recipients. All animals were given free access to water. After liver transplantation, rats in all three groups were fed normal rat chow. Four rats from each group were put to death on day 1 after operation. The levels of serum alanine aminotransferase (ALT), total bilirubin (TBIL) and the contents of malondialdehyde (MDA), tumor necrosis factor (TNF)-α in grafted liver tissue were observed. The other 8 rats in each group were kept for survival analysis. Experimental data were compared by ANOVA and followed by post hoc LSD tests. Overall survival rates were calculated using the Kaplan-Meier method, and comparisons were performed using the log-rank test. Results Moderate and severe degrees of liver steatosis were observed after 6 and 10 weeks high-fat feeding. The level of serum ALT on day 1 after operation was (614.5±70.6), (1 177.5±150.9) and (1 476.5±211.5) U/L in the control, MLF and SLF group, respectively. There was significant difference of ALT level among the three groups (F=33.9, P<0.01). The level of serum TBIL on day 1 after operation was (27.0±3.7), (48.5±7.5) and (59.0±11.5) μmol/L, respectively. Compare to the control group, the level of TBIL were significant higher in the MFL and SFL groups. Similar results were observed in the level of MDA and TNF-α in the liver tissue. There were 7 rats (7/8) survived for over one week in control group while only 3 rats (3/8) in MLF group and 1 rats (1/8) in SLF group. There was significant difference in the cumulative survival rates after operation among rats of the three groups. Conclusion The rat model of nonalcoholic fatty liver can be successfully established by high-fat diet feeding, which simulating the progression of nonalcoholic fatty liver in human being, and provide an ideal animal model for the research of clinical liver transplantation. Key words: Nonalcoholic fatty liver disease; Rat; Liver transplantation