Abstract: Abstract: Objective To investigate the effect of danfang (Dan) capsule on the expressions of wnt1, β-catenin and DKK1 in rat immune liver fibrosis and its possible mechanism. Methods Sixty clean grade SD rats were randomly divided into six groups: normal group, model group, low- Dan group, medium- Dan group, high- Dan group and positive drug group,10 rats per group. In addition to the normal group, the restgroups were intraperitoneally injected with pig serum to prepare rat models of immune liver fibrosis,and the normal group was intraperitoneally injected with the same amount of normal saline twice per week. At the same time, different concentrations (0.54, 2.16, 4.32 g/kg) of danfang capsules were given by gavage to low-Dan group, medium-Dan group and high-Dan group. Compound turtle shell soft liver tablet (0.54 g/kg) was given by gavage to positive drug group, while the same amount of saline was given by gavage to normal group and model group once a day for 12 weeks. Rats were killed by anesthesia at the end of 12 weeks. Liver histopathological examination was performed. Alkaline hydrolysis was used to measure the content of hydroxyproline (HYP). The immunohistochemistry staining, Western blot assay and qPCR were used to measure the expressions of wnt1, β-catenin and DKK1. Results Compared with normal group, the hepatic fibrosis was serious in model group, with increased HYP content, wnt1 and β-catenin expressions and decreased DKK1 expression (all P＜0.05). Compared with model group, there were no significant differences in liver fibrosis degree, HYP content, expressions of wnt1, β-catenin and DKK1 in the low-Dan group (P＞0.05).The fibrosis degree was significantly reduced in medium-Dan group and high-Dan group, and the HYP content and the expressions of wnt1 and β-catenin were reduced, while the expression of DKK1 was increased (all P＜0.05). Compared with the positive drug group, liver fibrosis was more severe in the low-Dan and medium-Dan groups, with increased HYP content,wnt1 and β-catenin expressions, and decreased DKK1 expression (all P＜0.05). There were no significant differences in these indicators between positive drug group and high-Dan group (P＞0.05). In the low-Dan，medium-Dan and high-dan groups, hepatic fibrosis was reduced in turn, HYP content, and expressions of wnt1 and β-catenin were decreased in turn,and DKK1 expression was increased in turn. There were significant differences among the groups in multiple comparisons(all P＜0.05). Conclusion Danfang capsule has a certain intervention effect on immune liver fibrosis in rats, with the mostsignificant effect at high dose. The mechanism may be related to the up-regulated expression of DKK1 and down-regulated expressions of wnt1 and β-catenin, thus inhibiting the activation of Wnt/β-catenin pathway.

Key words: danfang capsule, hepatic fibrosis, wnt1, β-catenin, DKK1