Abstract:
Aim :To investigate the pathological changes in NTBC[2-(2-nitro-4-trifluoro-methyl-benzoyl)-1,3 cyclohexanedione]-induced hepatic injury in mice and in the repopulation of adult hepatocytes in Fah
-/- mouse.
Methods :Autogenous hepatic injuries in Fah
-/- mice were induced by the treatment of NTBC.Injection of hepatocytes obtained from wild-type mice to spleen were transplanted into the Fah
-/- mice.Then,changes to body weight and the likelihood of the transplanted Fah
-/- mice,and hepatic immunohistochemistry were observed.In addition,pathological changes to liver damage induced by NTBC treatment were analyzed under HE-staining microscopy and electron microscopy.
Results :The surviving Fah
-/- mice subjected to hepatocyte transplantation were found to be healthy and in stable body weight.Liver repopulation reached to 90% in the 8th week.Repopulating hepatocytes caused no alteration to histological structure of the recipient liver,and subacute hepatic injury occurred in the Fah
-/- mice after NTBC treatment.Electronic microscopy observations indicated that necrosis in the hepatocytes occurred at early stage and that apoptosis gradually appeared.It was also shown both necrosis and apoptosis co-existed in the same samples of interest at the following stages of the induced liver injury.
Conclusion :Transplanted hepatocytes proliferated in Fah
-/- mice allow 90% of the hepatocytic repopulation.Repopulation renders normal hepatic function and structure in the recipient.Fah
-/- mice,as a model of liver repopulation,could be applicable in study of stem cell derived hepatic cells in transplantation assay.