Abstract: Objective: To investigate the protective effect of vitamin D receptor (VDR) activation on the bile duct ligation (BDL)-induced liver fibrosis in the mice, and to elucidate its possible mechanism. Methods: Sixty male C57BL/6 mice were randomly divided into sham operation group, sham operation+ paricalcitol group, model group (BDL) and treatment group (BDL+paricalcitol) (n=15).In sham operation, the abdominal cavities were opened but the bile duct was not ligated. In model group, the bile ducts of the mice were ligated with double lines and the middle of the bile duct was severed. The mice in sham operation+paricalcitol group and treatment group were intraperitoneally injected with the VDR agonist paricalcitol (200 ng·kg^-1, three time a week) 3 d before the operation and continued treatment for 5 d. The livers of mice were removed on the 5th day after bile duct ligation,and the morphology of liver tissue and the fibrosis degree were observed by HE staining and Sirus red staining. The levels of reactive oxygen species (ROS) in the liver tissue of the mice were detected by dihydroethidine (DHE) staining. Western blotting method was used to detect the expression levels of silence mating type information regulation 3 (Sirt3), 8-hydroxy guanine DNA glycosidase 1(OGG1), alpha-smooth muscle (α-SMA)and collagen Ⅰ (Col Ⅰ) in the liver tissue of the mice. Results: The HE staining results showed that the structure of liver cells was complete, no inflammatory cell infiltration; in model group, a large number of infiltrated inflammatory cells and spot-like focal necrotic areas were observed in the liver of the mice; compared with model group, the area of liver tissue necrosis in treatment group was significantly reduced and the infiltration of inflammatory cells was significantly decreased. The Sirus red staining results showed that there was only a small amount of fibrosis around the big bile duct in the liver tissue of the mice in sham operation group and sham operation+paricalcitol group; collagen deposition was obvious in the portal area of the liver tissue of the mice in model group;the collagen deposition around the bile duct of the mice in treatment group was reduced compared with model group.The DHE staining results showed that there was only a small amount of red fluorescence in the portal area in the liver tissue of the mice in sham operation group and sham operation+paricalcitol group; in model group, there were significantly more red fluorescence in the portal area and the area around the bile duct; the intensity of red fluorescence in level treatment group was lower than that in model group.The Western blotting results showed that the expression level of Sirt3 protein in liver tissue of the mice in model group was significantly lower than sham operation group and sham operation+paricalcitol group (P<0.05);the expression levels of OGG1, α-SMA and Col Ⅰ proteins were increased significantly(P<0.05);compared with model group, the expression level of Sirt3 protein in liver tissue of the mice in treatment group was significantly increased(P<0.05),and the expression levels of OGG1, α-SMA and Col Ⅰ proteins were increased obviously (P<0.05). Conclusion: VDR activation can reduces oxidative stress-induced hepatic stellate cell activation by increasing the Sirt3 protein; thereby reduces the BDL-induced liver fibrosis in the mice.

Key words: liver fibrosis, vitamin D receptor, silence mating type information regulation 3, oxidative stress, hepatic stellate cell