动物造模,药效评价,乙型肝炎 z-bio 2024-08-05 410

　　(1) Replication method: Tree shrews were inoculated with 0.5ml of serum from hepatitis B patients with positive hepatitis B B virus surface antigen (HBsAg) and hepatitis B B virus e antigen (HBeAg) via femoral vein. Three days later, an equal amount of the same serum was injected intraperitoneally once. After 10 days, draw blood once a week. One week before vaccination, draw blood from each animal as a self control; And randomly select 2 animals for liver biopsy as self tissue control. On the third weekend after vaccination, the ALT value increased from 3U to 188U. Starting from the fourth week, HBsAg appeared in the serum of tree shrews; Anti HBc appeared in the 8th week; HBeAg positive in the 14th week; At the 30th week, blood samples were collected and the serum HBV DNA was detected to be strongly positive using dot blot hybridization. In addition, in situ molecular hybridization was performed using biotinylated HBV DNA probes to detect HBV DNA in the cytoplasm of liver cells in model animals. Some model animals have mild inflammatory lesions in their liver tissue, such as ballooning, steatosis, eosinophilia, punctate or small focal necrosis, and inflammatory cell infiltration. Some animals have mild swelling in their liver cells. The liver of some model animals showed chronic hepatitis and mild fibrous tissue hyperplasia; In some liver tissues, liver cells are arranged in an glandular tube like pattern, with visible liver cell proliferation foci or nodules, and a small number of scattered or clustered atypical liver cells.

　　(2) Model characteristics: HBsAg, anti HBs, or HBV DNA can be detected in the blood of model animals infected with HBV; Immunohistochemical detection of liver tissue shows HBsAg and/or HBcAg; Southern hybridization can detect HBV DNA in integrated form from liver tissue; Model animals may experience elevated serum ALT levels.

　　(3) After vaccination with human HBV, the conversion of serological markers in juvenile tree shrews is similar to that of acute self limiting hepatitis B in humans. The duration of HBV in most infected animals is relatively short, and the liver pathological changes in most infected animals are mild, making it difficult to form chronic hepatitis or chronic HBV carrier status. In adult tree shrews, viral antigenemia quickly transforms into anti HBe, anti HBs, and anti HBc anemia. Juvenile tree shrews are more susceptible than adult tree shrews. After being infected with HBV, the serum HBsAg positivity of juvenile tree shrews can last for 10 weeks, while adult tree shrews can turn positive for serum anti HBs within 2-3 weeks. Tree shrews are superior to groundhogs, ducks, and other primates in terms of biological evolution, belonging to lower primates and closer to humans in taxonomy. They can be infected with human HBV and are expected to become a reliable animal model for human HBV.