动物造模,非人灵长类感染模型 z-bio 2021-11-23 308

　　(1) Breeding method Collect adult rhesus monkeys, cynomolgus monkeys and bear monkeys with negative HAV, HBV, HCV, HDV and HEV 1 month before vaccination and 1 day before vaccination, and determine their normal ALT enzyme activity . Under ketamine anesthesia, the plasma of hepatitis B patients was injected intravenously into experimental monkeys at a dose of 5 ml/kg body weight. Blood was drawn for the first week after the virus inoculation and every 7 days thereafter.

　　(2) Model characteristics: In the first week after vaccination, the ALT of the model animals rises, reaches a peak in 2-6 weeks, and then fluctuates repeatedly. Two weeks after vaccination, these animals began to become positive. Anti-HCV IgG peaks at 10-12 weeks, and serum HCVNA is repeatedly positive. After 7 weeks, liver biopsy under an optical microscope showed histopathological changes. Observing the ultra-fine structure under an electron microscope shows that the endoplasmic reticulum of liver cells has proliferated and expanded. Immunohistochemical staining shows the liver. The cells are positive for HCVS3 antigen. Five months after vaccination and infection, liver biopsies of model animals showed chronic inflammatory changes. Observation of ultra-fine structure showed that hepatocyte glial fibrous tissue proliferated. After 11 months, chronic inflammation was less than before. In addition to abnormal ALT, model monkeys can also detect anti-HCV-IgG antibodies and HCV-RNA in serum, as well as pathological changes in liver tissue microstructure and ultrastructure. This indicates that HCV can artificially infect experimental monkeys.

　　(3) After comparing medical vaccination with HCV infection, most experimental monkeys showed transient gastrointestinal symptoms, manifested as anorexia, and a few animals lasted longer, but the degree was relatively mild. Two weeks after vaccination, the characteristics of serum ALT elevation in rhesus monkeys, cynomolgus monkeys, and bear monkeys were similar to those of humans and chimpanzees infected with HCV. Rhesus monkeys are the most abundant and widely distributed species of primates in my country. They are relatively easy to reproduce under laboratory conditions, medium size and easy to operate. This is an ideal HCV animal model.