Abstract: Objective:To explore the changes of levels of endogenous N-acetyl-seryl-aspartyl-lysylproline (AcSDKP) and its regulatory factors in liver tissue of rats with liver fibrosis induced by bile duct ligation, and to elucidate the effect of endogenous AcSDKP in the pathologic process of liver fibrosis. Methods:Forty-five healthy male rats were randomly divided into model group (the liver fibrosis rat models were set up by bile duct ligation), blocking group (the liver fibrosis rat models were treated with angiotensin-converting enzyme inhibitor before) and control group (the rats received laparotomy but not bile duct ligation); each group had 15 rats. The serum and liver tissue of the rats in various groups were gained at the 1st week, 2nd week and 4th week. The differences in the indexes of liver function, the liver fibrosis degrees,and the AcSDKP levels in liver tissue of the rats in various groups were analyzed. The levels of thymosin beta 4 (Tβ4), prolyl oligopeptidase (POP) and angiotensin converting enzyme (ACE) in liver tissue of the rats in various groups were detected by Western blotting. Results:The levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST) and total bilirubin(TB) of the rats in model group were higher than those in other two groups from the 1st week (P<0.05), and there were no differences between blocking group and control group (P>0.05). The ALB and the AcSDKP level in liver tissue of the rats in model group were lower than those in other two groups from the 2nd week (P<0.05), and there were no differences between blocking group and control group (P>0.05).The levels procollagen type Ⅲ(PCⅢ), collagen type Ⅳ(CⅣ) and hyaluronic acid(HA) in three groups had no differences at the 1st week (P>0.05). The levels of PCⅢ, CⅣ, and HA of the rats in model group were higher than those in other two groups from the 2nd week (P<0.05), and there were no differences between blocking group and control group (P>0.05). The levels of Tβ4 and ACE in liver tissue of the rats in model group were higher than those in other two groups from the 2nd week (P<0.05), and the level of POP of model group were lower than those in other two groups from the 2nd week (P<0.05), but there were no differences between blocking group and control group (P>0.05). The liver tissue of the rats in model group was basically normal at the 1st week, showed the focal necrosis at the 2nd week, and showed the flake necrosis at the 4th week. The liver tissue of the rats in blocking group and control group were basically normal at all time points. Conclusion:The endogenous AcSDKP level in the liver fibrosis rats induced by bile duct ligation is down-regulated through the axis of Tβ4-POP-AcsDKP.

Key words: N-acetyl-seryl-aspartyl-lysylproline, liver fibrosis, thymosin beta 4, disease model,animals