Abstract: Objective To investigate the dynamic changes of expression and activity of prolyl endopeptidase （PREP） in the liver tissues of mice with non-alcoholic fatty liver disease （NAFLD）. Methods 40 male C57BL/6J mice were randomly divided into standard diet-fed and high fat diet-fed group. The animals were scarified at the end of 4 weeks and 16 weeks. The levels of serum biochemical index were measured by biochemical analyzer. Hematoxylin-easin staining,real-time polymerase chain reaction,western blot or Suc-Gly-Pro-AMC substrate method were applied to determinate the liver histological alterations,mRNA levels,protein expressions and activity of PREP,respectively. Results At the end of 4 weeks,the body weight,liver weight,alanine aminotransferase （ALT）,triglyceride （TG）,total cholesterol（TC） and fasting blood glucose （FBG） in mice in model group were similar with those in the control group; the liver tissues in model group showed mild steatosis with increased NAFLD activity score （NAS） of （3.43±0.79） as compared with that in the control group; relative levels of PREP mRNA,protein and activity had no statistical significance as compared with those in the control group;at the end of 16 weeks,the body weight,liver weight,ALT,TG,TC and FBG in model group were（32.93±2.72） g,（4.64±0.46） %,（53.64±22.01） IU/L,（1.18±0.17） mmol/L,（4.34±0.44） mmol/L and （5.67±0.87） mmol/L, respectively,significantly higher than those in the control group [（28.19±1.23） g,（4.02±0.11） %,（28.60±4.01） IU/L,（0.99±0.15） mmol/L,（2.94±0.18） mmol/L and （4.26±0.65） mmol/L,respectively,P<0.05];the NAS score in the model group was（5.60±1.43）,significantly higher than that in the control group [（0.40±0.70）,P<0.01];although the hepatic PREP protein expression was not statistically elevated both at 4 and 16 weeks, the relative levels of PREP mRNA and activity of the enzyme in the liver tissues of model group were increased to （1.81±0.34）-and （1.36±1.78）- fold of those in the control group at 4 and 16 weeks, respectively. Conclusion The dynamic changes of PREP activity in the mouse liver might participate in the progression from non-alcoholic fatty liver to non-alcoholic steatohepatitis.

Key words: Non-alcoholic steatohepatitis, Prolyl endopeptidase, Liver, Mice