Résumé
Objective:To evaluate the feasibility of animal model of bilirubin encephalopathy by injecting bilirubin solution into cerebellomedullary cistern of neonatal full-term and premature mice.Methods:Thirty 7-day-old mice were randomly divided into 5 groups:control group,model group 1,model group2,model group3,and model group4.Bilirubin solution was injected into the cerebellomedullary cistern in model groups(bilirubin 20?g/g bodyweight),while equal volume of normal saline was injected into the cerebellomedullary cistern in control group.The mice in model groups were sacrificed at the time of 12h,24h,48 and 72h after injection,respectively,and those in control group were sacrificed at 24h after injection.The apoptosis and necrosis of neurocytes,the expressions of Bcl-2 and Bax proteins were detected by HE stain,immunohistochemical method and TUNEL in the hippocampus,respectively.Preterm mice were delivered by cesarean section at 21 days gestation and fed by surrogate mother mouse until 7 days old.Bilirubin solution was injected into their cerebellomedullary cistern.The mice's abnormal behaviors were observed.Results:The mice of model groups and preterm group appeared abnormal behaviors in different degree.Under light microscope,the neurocytes in their hippocampus appear apoptosis and necrosis.The nissl body in pyramidal cell body and dendron decreased,even dissolved to disappear.TUNEL showed that the apoptosis rate in the hippocampus increased obviously at 12h post-injection,reached the peak at 24h post-injection.The positive rate of Bax protein in the hippocampus reached the peak at 24h post-injection,while the positive rate of Bcl-2 protein decreased to the lowest.Conclsions:The method that injecting bilirubin solution into neonatal mice' cerebellomedullary cistern to set up the animal model of bilirubin encephalopathy is simple and feasible.The peak time of neurocytes' apoptosis in hippocampus was 24h post-injection.It's crucial to prevent bilirubin encephalopathy as early as possible.