Influences of retrorsine on mouse hepatocyte proliferation after liver injury / 第二军医大学学报

ABSTRACT

Objective:To compare the influences of retrorsine on hepatocytes proliferation in mice and rats after liver injury,so as to investigate the feasibility of using retrorsine for establishment of liver cell transplantation model in mice.Methods: Male mice and rats were pretreated with 2 injections of retrorsine(70 mg/kg for mice and 30 mg/kg for rats)(as retrorsine-treated group,n=30) at 2 weeks interval or saline(as nontreated group,n=30).A single injection of carbon tetrachloride(CCl_(4), 0.5 mg/kg) was given to all animals 4 weeks after the final injection of retrorsine or saline.At 0(before administration),1,2,3,4,6,15 d after CCl_(4) administration,the animals were sacrificed and their livers were subjected to H-E staining and Ki-67 antibody immunohistochemistry analysis to evaluate the pathological changes and hepatocyte proliferation.Results: The liver in rats treated with retrorsine displayed obvious megalocytosis,small bile duct hyperplasia,and small hepatocyte hyperplasia(forming nodule);no such changes were found in non-treated group.However,the liver in mice treated with retrorsine displayed hepatocyte degeneration and necrosis in the perivenous areas and the same was true to the liver in non-treated mice.Ki-67 immunohistochemistry analysis showed that in rats treated with retrorsine,the positive hepatocytes,mainly found in small hepatocyte nodules,were obviously less than those in control group 3 d after CCl_(4)administration(P