Comparison of hepatobiliary injury for newborn BALB/c mice which induced by different titers of rhesus rotavirus

Abstract

Objective To compare the hepatobiliary injury difference of newborn BALB/c mice infected by different titers of rhesus rotavirus(RRV). Methods Neonatal mice(n=80) were randomly separated into 4 groups and were intraperitoneally inoculated with different titers of rotavirus: High titer group(1×107 PFU/ml); Medium titer group(1×106 PFU/ml); Low titer group(2.5×105 PFU/ml); Control group (only culture medium) within the first 24 hours after birth. All mice were sacrificed at day 12 after RRV inoculation then the liver and blood samples were collected. Meanwhile, mice were observed daily for at least 12 days, including their weight, skin color and survival situation. Liver functions were examined by serum biochemical test and morphologic changes in the biliary tract were observed. Tissue sections underwent H&E staining and immunohistochemically analysis for the presence of CK19. Results Compared with the normal mice, the mice in the experimental group had different degrees of skin jaundice, weight lost, survival rate decreased, liver function damage. In the experimental group, the symptom of low titer group was light, and could be restored to normal, however, when compared with the low titer group, the mice in the high titer group were serious, their skin jaundice was more obvious, weight was significantly reduced and irreversible, survival rate was lower(50%), liver function of TBIL, DBIL, TBA, ALT, ALP were significantly increased.Further analysis showed that the high titer group had high bile duct obstruction rate (80%), with no case of obstruction in the low titer group. Histologic analysis also showed intrahepatic bile duct atresia in the high titer group, a large number of inflammatory cell infiltrated around the portal area, while the morphology of intrahepatic bile duct was almost normal and just a small amount of inflammatory cell infiltrated around the portal area in the low titer group. Conclusions Different titers of rotavirus had different effects on the newborn mice hepatobiliary system: high titer was easy to cause biliary atresia, and low titer caused hepatitis. Key words: Rotavirus; Biliary atresia; Neonatal hepatitis