动物造模,食蟹猴模型 z-bo 2022-04-27 489

　　[Model mechanism] Hepatitis A is mainly transmitted through the fecal-oral route (gastrointestinal tract), but other routes include blood and vertical transmission. Taking advantage of the infectivity of hepatitis A, animals can be infected with hepatitis A virus through intravenous injection of fresh fecal filtrate from hepatitis A patients or forced feces of hepatitis A patients, and natural persons can develop similar diseases after infection.

　　[Modeling method] Dilute the stool of patients with hepatitis A with PBS (10M sodium phosphate, 0.15 MaCl), penicillin (100 IU/ml), and streptomycin (100 mg/ml) to a concentration of 1%, and centrifuge slowly The supernatant was filtered through a 0.45 μm filter membrane. HAV filtrate was detected by enzyme-linked immunosorbent assay and real-time quantitative PCR. The experimental group was intravenously injected with 0.5 ml virus filtrate, and the control group used normal fecal filtrate.

　　[Model characteristics] When cynomolgus monkeys are infected with HAV, alanine aminotransferase (ALT) increases on day 7 and reaches a peak on day 20, while IgM and total HAV antibodies increase on day 14. After reaching a peak on the 20th day, it gradually decreased. HAV nucleic acid was detected in the stool on the 7th day, the virus amount in the stool reached 100,000 copies/ml on the 15th day, the serum load reached 10000 copies/ml on the 20th day, and the saliva was loaded with 1000 copies/ml on the 7th day. HAV antigens were continuously detected in the liver and salivary glands 7 to 60 days after infection. HAV replication intermediates can be detected in the liver, salivary glands, tonsils and lymph nodes, and they can be used as target organs for early replication of HAV outside the liver. Pathological examination of liver tissue showed swelling of liver cells and inflammatory cell infiltration in the portal area.

　　[Model Evaluation and Application] Cynomolgus monkeys are closer to humans than rodents in terms of system evolution and immune regulation, and are more intuitive for immune regulation and virus replication in humanoids after infection. It can be reflected in the study of the pathogenic mechanism of hepatitis A and the evaluation of the efficacy of hepatitis A vaccine.