动物造模,药效评价,小动物感染 z-bio 2024-08-21 394

　　(1) Replication method Five kinds of small animals, namely guinea pigs, albino hamsters, black line hamsters, rats, Brandt's voles and chickens, were infected with 10 5.7 power TCID50/ml SARS-CoV BJ201 strain through nasal drip. The infection doses were 0.5 ml for guinea pigs, 0.2 ml for albino hamsters, 0.2 ml for black line hamsters, 0.3 ml for rats and 0.2 ml for chickens. Brandt's voles (adults and infants) were treated with nasal spray method. Observe and record the clinical manifestations of infected animals in detail every day after infection. On the 14th day after infection, the model animals were euthanized painlessly, dissected, and observed with the naked eye. Tissue pathology and virus nucleic acid testing were performed on the lungs, spleens, lymph nodes, and pharynx of the model animals. After vaccination, guinea pigs developed pulmonary edema; The Brandt's vole died after being poisoned. Manifesting as bleeding from the mouth, nose, and intestines, the lung tissue shows hemorrhagic interstitial pneumonia changes, and the liver, spleen, kidney, and pancreas tissues all show congestion changes; The lung tissue of surviving animals showed interstitial pneumonia, focal bleeding, and emphysema changes. There is no pathological damage to the tissues and organs of other animals. Virus nucleic acid can be amplified from the lung tissues of infected rats, guinea pigs, and Brandt's voles, while the amplification results of other infected small animal tissues are all negative. The results of SARS antibody testing on the serum of hamsters and rats infected for 2 weeks were both positive.

　　(2) The model features that SARS virus can infect multiple organs of Brandt's voles, such as lungs, liver, spleen, kidneys, pancreas, lymph nodes, etc., and can cause organ damage. Except for the significant pathological changes observed in the Brandt's vole, no obvious ocular pathological changes were observed in other infected small animals, but humoral and cellular immunity were produced. SARS virus antibodies were detected in the serum of hamsters and rats infected for 2 weeks, and viral RNA was amplified from their lung and pharyngeal tissues, indicating that SARS CoV can replicate in these animals and provide a basis for further research on SARS small animal models.

　　(3) During the 2-week modeling observation period in comparative medicine, all infected small animals did not exhibit clinical symptoms and viremia similar to SARS characteristics such as high fever, dry cough, and difficulty breathing. However, rats and Brandt's voles showed similar serological, immunological, and pathological changes as human SARS patients, making them suitable animal models for SARS research. In addition, artificial infection experiments on BALB/c mice, domestic cats (Felis domesticus), and ferrets (Mustela furo) have shown that all three animals are susceptible to SARS CoV. Among them, viral replication can be found in the lungs and intestinal tissues of BALB/c mice infected with SARS CoV. Although domestic cats (Felis domesticus) have no obvious clinical manifestations like BALB/c mice, they can detoxify and infect other healthy individuals, which is consistent with the results of rats and Brandt's voles.