ANIT-induced cholestasis model in different periods of pathology and its natural recovery
Objective The aim of this study was to establish an animal model simulating cholestasis and its natural recovery cycle,and to investigate the pathological mechanism of cholestasis,to provide a scientific basis for the clinical prevention and treatment of this disease.Methods KM male mice aged 6~8 weeks with a body mass of 18~22 g were selected and divided into 3 groups according to the recovery time nodes(0,2,4 w)after modeling.Each group was divided into 3 subgroups,which received different doses(10,20,30 mg/kg)of α-naphthyl isothiocyanate(ANIT)by gavage treatment for 4 weeks to establish cholestatic liver injury(CLI)model.ANIT treatment was stopped after the 4th week.Liver and serum samples were collected at the 4th,6th,and 8th week,respectively,to observe the pathologic changes of liver histology and to detect serum biochemical indexes and tissue inflammatory factors.Results Pathology showed that inflammatory cell infiltration and bile duct epithelial cell proliferation intensified with the increase of ANIT dose.Biochemical indexes such as hepatic drug enzymes and inflammatory factor levels increased with the increase of ANIT dose,but some of the detected indexes were gradually recovered with the prolongation of the recovery period after cessation of modeling.Conclusion The cholestasis model mice induced by ANIT at a dose no greater than 20 mg/kg for 4 weeks had natural recovery.