The Regenenration Of Hepatic Oval Cells In PH/RS Mouse Model

Objective: To create a mouse model for liver injury and oval cell proliferation by treating with retrorsine and partial hepatectomy(RS/PH). To study the liver regeneration and oval cells proliferation after being treated with retrorsine, so as to investigate the relationship between oval cell and liver regenenration.Methods: Female C57BL/6 mice, 8 weeks old, were divided into two groups Randomly: PH group and RS/PH group. Mice in RS/PH group were treated with 2 injections of retrorsine, 70 mg/ kg at 2 weeks interval,mice in PH group were treated with saline instead of retrorsine. Two thirds partial hepatectomy was given to all animals 4 weeks after the final injection of retrorsine or saline. At 3, 7, 14d after partial hepatectomy, the animals were sacrificed and their livers were subjected to H-E staining, BrdU, CK19, CD34 and c-kit antibody immunohistochemistry analysis to evaluate the pathological changes, the hepatocyte and oval cell proliferation and .Results:1. In RS/PH group, the liver in mice displayed obvious hepatocyte balloon degeneration, necrosis and small bile duct hyperplasia. Severe oval cells were found in hepatic lobule, hepatic sinusoid and epithelium of small bile duct. No such changes were found in PH group. BrdU immunohistochemistry analysis showed that in mice treated with retrorsine and partial hepatectomy, the positive hepatocytes were obviously less than those in PH group at every point after partial hepatectomy ( P < 0. 05). 2.Visible oval cells proliferation were seen in mice of RS/PH group and stained positive for CK19,C-kit,CD34. First of all, hepatic oval cells appeared in portal area, specifically in the small bile duct epithelium or hepatic sinusoid. Then grew into the hepatic lobule and differentiated into hepatic cells gradually. Mice in PH group were not observed.Conclusions: 1.Retrorsine can obviously inhibit hepatocyte regeneration after liver injury in mice.2.The model of mice treated with retrorsine and partial hepatectomy could induce oval cells proliferation.3.When hepatocyte regeneration been inhibited, oval cell can proliferate and rebuild the injured liver.