The Anti-fibrotic Effect Of Collagen-binding Vascular Endothelial Growth Factor In Mice With Carbon Tetrachloride-induced Liver Fibrosis

Objective:To investigate the anti-fibrotic effect of collagen-binding vascular endothelial growth factor (CBD-VEGF) in mice with carbon tetrachloride (CCl4)-induced liver fibrosis.Methods:For induction of liver fibrosis, CCl4 (5μl/g, diluted 1:5 in olive oil) was injected intraperitoneally to the BABL/c mice twice weekly for 12 weeks. After 12 weeks of CCl4 injection, mice were randomly assigned into two groups:the normal saline (NS) group and the CBD-VEGF group. Mice in NS group and CBD-VEGF group were injected by 50μl NS or CBD-VEGF into the liver tissues respectively. Mice were sacrificed and the livers were collected for histological evaluation after 4 and 8 weeks of CBD-VEGF injection.Results:Liver fibrosis was successfully constructed in the mice after 12 weeks of CCl4 injection. After 4 weeks of CBD-VEGF injection, the ALT and AST levels in the CBD-VEGF group were higher than the NS group. However, after 8 weeks of CBD-VEGF injection, the ALT and AST levels were not significantly different between the NS group and CBD-VEGF group. HE staining showed that the inflammation of the liver in the CBD-VEGF group was slighter than NS group after 4 and 8 weeks of CBD-VEGF injection. Masson’s trichrome staining indicated that the deposition of collagen in the CBD-VEGF group was also slighter than NS group after 4 and 8 weeks of CBD-VEGF injection. Immunohistochemistry staining demonstrated that blood vessel density in the CBD-VEGF group was significantly higher as compared with NS group (p<0.01). The numbers of proliferative hepatocytes in CBD-VEGF group were significantly larger than NS group (p<0.01). TUNEL assay showed that the hepatocyte apoptosis in the CBD-VEGF group was smaller than NS group.Conclusions:CBD-VEGF injection could attenuate liver fibrosis of CCl4-induced fibrosis in mice. The anti-fibrotic effect of CBD-VEGF may be related to reduceing HSCs activation, protecting hepatocyte from apoptosis and promoting hepatocyte regeneration and angiogenesis. CBD-VEGF may provide a potentially therapeutic strategy for liver fibrosis.