动物模型 z-bo 2020-07-31 556

　　At present, the animal models of hepatitis B virus mainly include sh hepatitis B model, duck hepatitis B model, marmot hepatitis B model and mouse hepatitis B model.

　　[Modeling mechanism] Hepatitis B virus (HBV) is mainly transmitted through blood and blood products, and it is injected into animals through intravenous injection or hydrodynamic high-pressure injection using HBV patient serum or HBV DNA. I will.

　　[Modeling method]: Transfer 0.5 ml of serum from hepatitis B patients who are positive for both hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg) from the femoral vein to sh. I will be vaccinated. Zun: Duck hepatitis B virus (duck hepatitis B virus, DHBV) is injected into ducks through intravenous injection, intramuscular injection, intraperitoneal injection, intrahepatic injection and intravenous injection of duck embryos. Woodchuck (Woodchuck): The woodchuck hepatitis virus (WHY) is another hepatotrophic DNA virus discovered after human HBV. Woodchuck long-term infected with WHV can gradually develop severe hepatitis and liver cancer, just like the pathogenesis of human infection with HBV. By inoculating young woodchucks with WHV, a model of woodchuck hepatitis can be obtained. Hydrodynamic method of transfection mouse model: High-pressure hydrodynamic method can inject HBV plasmid DNA into the tail vein of mice, and HBV DNA can be detected in the serum after injection.

　　[Model Features]: After HBV infection, HBsAg, anti-HBs or HBV DNA will be detected in the blood. HBsAg and/or HBcAg can be confirmed on liver tissue by immunohistochemistry. Serum ALT increased and Southern blot was detected. HBV DNA is integrated in liver tissue. The wooden sh model allows low-cost, convenient experimental operations, and is not strictly limited to animal ethics.

　　Zun: The infection rate of ducks at the age of 1 day after DHBV vaccination is close to 100%, they can maintain viremia for a long time, and DHBV DNA can also be detected in the liver. After 5 days of inoculation, the activity of DHBV DNA and endogenous DNA polymerase decreased, and 14 days of inoculation did not cause viremia. After being infected by the virus, the human body will simultaneously develop corresponding virus-specific humoral and cellular immune responses, thereby producing duck DHBsA9. You can maintain it for 22 weeks. Marmot: When infected with WHV, WHsAg antigenemia occurs, and the characteristic surface and core particles of WHV can be confirmed by electron microscopy.

　　Dynamic hydrodynamic transfection mouse model: high titer virus after HBV infection, HbsAg in vivo is maintained for more than 6 months, and HBV replication and transcription intermediates in vivo can be detected for up to 1 year. [Evaluation and application of the model] In 1996, Walter et al. vaccinated Tree Java with human HBV vaccine in adulthood. The result was similar to human acute self-limited hepatitis, but the adult vaccination report showed that it showed temporary Sexual infection. Inoculation of saplings and surrounding trees with HBV can increase the infection efficiency. Newborns have been vaccinated with human HBV, and the virus already exists in animals and can replicate stably. In 2012, hepatitis B virus and hepatitis D virus co-receptor sodium taurocholate cotransport peptide was found in primary mouse liver cells, which is expected to become a reliable animal model of human HBV. The post-DHBV viremia of ducks is related to the age of ducks, and the time of DHBV infection is an important factor affecting its prevalence and prognosis. After intraperitoneal injection of DHBV into 1-day-old ducks, the positive rate was about 89% after 2 weeks and about 94% after 4 weeks, lasting 22 weeks. The positive rate at 10 days after infection was approximately 16% within 2 weeks, 38% within 4 weeks, and 61.1% within 6 weeks. After 12 weeks, about 1/2 of the DHBV-positive ducks showed DHBsA9 and DHBV DNA transfer. shadow. The duck model has a high DHBV infection rate and is easy to feed. It is an excellent model for evaluating the effect of antiviral drugs in the preclinical stage. However, there are significant differences in the structure of DHBV avian hepatitis virus and human HBV. Ducks are evolutionarily different from humans, which makes it difficult to replicate the human HBV infection process.

　　WHV infection is mainly a chronic infection of newborn woodchucks. It is used to study the chronic mechanism of HBV, to develop HBV vaccines and antiviral drugs, and to study the life cycle of HBV, molecular mechanisms, infection and carcinogenic mechanisms. I can do it. However, animal models of woodchuck hepatitis virus cannot be directly infected with HBV. There are still some differences between WB and HBV, which cannot fully simulate the pathological process of HBV. Hydrodynamic transfection mouse model: This model can be used to study the life history of HBV (a mechanism of chronic infection), identify mutant HBV-DNA and identify single or multiple genes in the process of HBV infection. You can study the mechanism of action. Since it is a multifunctional mouse of the immune system, it can be used to study the mechanism of viral immune effects.