动物造模 2020-08-11 520

　　(1) Replication method Take five species of small animals, including guinea pigs, albino hamsters, black-lined hamsters, rats, Brandt's voles and chicks, and infect them with 10 5.7 power TCID50/ml SARS-CoV BJ201 strains respectively through intranasal drops. The infectious doses were 0.5ml for guinea pigs, 0.2ml for albino hamsters, 0.2ml for black-lined hamsters, 0.3ml for rats and 0.2ml for chicks, and Brandt's voles (adults and juveniles) were sprayed in the nasal cavity. After infection, observe and record the clinical manifestations of infected animals in detail every day. The model animals were sacrificed painlessly on the 14th day after infection, and gross observation was performed after dissection. The lung, spleen, lymph nodes and pharynx of the model animals were taken for histopathological observation and virus nucleic acid detection. Guinea pigs developed pulmonary edema after vaccination and infection; Brandt's voles died after challenge. Hemorrhage in the mouth, nose and intestine, lung tissue showed hemorrhagic interstitial pneumonia changes, liver, spleen, kidney, and pancreas tissues showed congestive changes; lung tissue of surviving animals showed interstitial pneumonia, focal hemorrhage and lungs Emphysema changes. The tissues and organs of other animals had no histopathological damage. Viral nucleic acid can be amplified from the lung tissues of infected rats, guinea pigs, and Brandt's vole. The amplification results of other infected small animal tissues are all negative. The results of SARS antibody detection on the serum of hamsters and rats 2 weeks after infection were all positive.

　　(2) Model characteristics SARS virus can infect multiple organs of Brandt's vole, such as lung, liver, spleen, kidney, pancreas, lymph nodes, etc., and can cause organ damage. Except for Brandt's voles, which had obvious pathological changes, no obvious eye pathological changes were observed in other infected small animals, but humoral immunity and cellular immunity were produced. The hamster and rat serum after 2 weeks of infection can The detection of SARS virus antibodies and the amplification of viral RNA from lung and pharynx tissues indicate that SARS-CoV can replicate in these animals, which can provide a basis for further research in small animal models of SARS.

　　(3) Comparative medicine. During the 2-week modeling observation period, all infected small animals did not show clinical symptoms and viremia characteristic of SARS such as high fever, dry cough, and dyspnea. However, rats and Brandt's voles showed similar symptoms. The similar changes in serology, immunology, pathology and other aspects of human SARS patients can be used as animal models for SARS research. In addition, artificial infection tests on BALB/c mice, domestic cats (Felis domesticus) and ferrets (Mustela furo) have shown that these three animals are all susceptible to SARS-CoV, and BALB/c mice After being infected with SARS-CoV, virus replication can be found in their lungs and intestinal tissues. Although domestic cats (Felis domesticus) have no obvious clinical manifestations like BALB/c mice after infection, they can excrete toxins and can infect others In healthy individuals, this behavior is consistent with the results of rats and Brandt's voles.