【Animal Experiment】-Macaque Hepatitis B Model
动物实验,乙型肝炎
z-bo
2020-08-11
502
(1) Replication method 2ml of HBV positive serum was intravenously inoculated into healthy macaques weighing 2 to 4 kg, aged 1 to 3 years, and having negative HAV, HBV, and HCV markers. The inoculated HBV positive sera were taken from asymptomatic HBV carriers, and their HBsAg, HBeAg, anti-HBc, and HBV-DNA were strongly positive. Model monkeys were subjected to liver puncture and liver resection under ketamine anesthesia before vaccination and 4, 8, 12 weeks after vaccination. The specimens were fixed with 10% formaldehyde solution, and were used for regular tissue sectioning, stained with HE, and observed under light microscope; in addition, liver tissue was taken for ultrathin sectioning under transmission electron microscope. Observe under the electron microscope.
(2) Model characteristics During the observation period of infection, the model monkeys did not show signs of jaundice, poor appetite, lack of energy, weight loss, etc. After rhesus monkeys are infected with HBV, there are no obvious symptoms of hepatitis, and the acute hepatitis lesions are mild. Some model animals have a transient increase in ALT. Observation under light microscope showed that some liver tissues showed mild hepatitis lesions, the liver cells showed balloon-like changes, some areas were a little necrotic, and the lobular boundary plate was still intact. Under the electron microscope, there are many round, tube-shaped and intact hepatitis B virus particles (Dane particles). Dane particles are significantly reduced at 1 week after infection, and there are still a few round particles at 8 weeks, but there are no Dane particles. Immunohistochemistry detected HBsAg expression in liver cells, and in situ hybridization detected HBV DNA in liver cells. HBsAg was continuously positive in the blood for 7 to 8 weeks.
(3) Comparative medicine When HBV enters the body of a model animal, the body's reticuloendothelial system, especially fixed phagocytes (liver macrophages) in the liver, can remove HBV from the blood circulation and prevent the virus from entering liver cells. In terms of humoral immunity, the anti-S1 and anti-S2 antibodies produced by activated B cells can play an important role in the early anti-HBV infection. Therefore, the success of the HBV infection model is closely related to the age, weight, and immune system of the model animal. The pathological changes of liver tissue in this model are basically similar to those of human hepatitis B. In addition to macaques, higher non-human primates such as chimpanzees, gibbons, and woolly monkeys can also establish human HBV infection animal models. Among them, chimpanzees are the most sensitive, but due to moral, economic and experimental conditions that are difficult to control, these higher primates The application of animal HBV infection models is limited.
