Objective: To investigate the protective effects of curcumin on bile duct ligation(BDL)-induced liver cholestasis in mice, so as to provide a new treatment strategy for liver fibrosis.
Methods: Forty-two healthy adult male BALB/c mice were randomly divided into sham group (n =6), sham+curcumin group (n=6), BDL treatment group (n=10), BDL+curcumin group(n=10), BDL+curcumin+ZnPP group (n=10). Seven days after BDL operation, the sham operation + curcumin group and the BDL+ curcumin group were treated with curcumin at the dose of 30 mg/kg by intraperitoneal injection once a day for 7 days.The mice in BDL+ curcumin +ZnPP group were treated with curcumin (30 mg/kg) and ZnPP (50 μmol/kg) by intraperitoneal injection once a day for 7 days. For the sham group and the BDL group, mice were treated with equal-volume saline daily by intraperitoneal injection. After 14 days of BDL, the plasma and liver tissues were collected, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. The pathological changes of liver tissue and liver fibrosis were observed, and the protein expression of HO-1 in liver tissue was detected.
Results: Compared with the sham group, mice in the BDL group had enlarged liver gallbladder and the serum levels of ALT and AST were increased significantly (P＜0.05). Meanwhile, the results of Sirius red staining and qRT-PCR of pro-fibrosis related genes showed collagen deposition in the liver, and immunohistochemistry of macrophages and neutrophils showed inflammatory cell infiltration in the liver. Compared with the BDL group, the serum levels of ALT and AST in the curcumin treatment group were decreased significantly (P＜0.05), collagen deposition and inflammatory cell infiltration were improved, and HO-1 expression was increased (P＜0.05) after curcumin treatement. In the curcumin treatment group, the protective effect of curcumin on liver injury could be reversed by HO-1 active inhibitor ZnPP.
Conclusion: Curcumin can improve liver inflammation and fibrosis caused by BDL, and this protective effect is related to the regulation of HO-1 activity by curcumin.