动物模型 z-bo 2020-08-11 557

　　(I) Replication method Kunming suckling mice 48-72h after birth are inoculated into their brains with 0.02ml of Hantavirus 76/118 strain (LD5010 -6.5 power/0.02ml) that has been adapted to suckling mice. After inoculation, the brain tissue of suckling mice has typical changes in viral encephalitis. Histopathological observation under light microscope showed that there were diffuse venules, telangiectasias and congestion in the brain tissue, widening of small blood vessel spaces, small focal hyperplasia of glial cells, and degeneration of some nerve cells; scattered hemorrhages and hemorrhages were found in lung tissue. Alveolar septal small blood vessels are congested and dilated; renal tubular epithelial cells in renal tissue have watery degeneration, and casts can be seen in the renal tubule lumen. Brain tissue lesions first appeared on the second day after viral infection, manifested as extensive subcortical eosinophilic changes in nerve cells, cytoplasm and nucleus constricted and red stained, and volume reduced; scattered eosinophilia under the cortex began to appear on the fourth day Necrosis, focal necrosis began to appear in the hippocampal gyrus; typical apoptotic bodies began to appear on the 6th day, and the lesions were gradually aggravated, manifested as widely distributed focal eosinophilic necrosis, in which black dot-like apoptotic bodies were seen , The number of nerve cells in the cerebral cortex is significantly reduced, and the cortex becomes thinner. Electron microscopic ultrastructural observation shows that the endoplasmic reticulum and Golgi apparatus of the hippocampal gyrus of the neonatal rat brain expand and proliferate, and virus particles can be found in the Golgi apparatus.

　　(2) Model characteristics The pathological changes of this model are the most obvious in brain, lung, and kidney tissues, and the changes are characterized by congestion and hemorrhage of small blood vessels in the damaged organs; virus antigens are widely distributed in various organs (brain, heart, liver, Spleen, lung, kidney, thymus). Therefore, the suckling mouse HV model has been successfully used for virus isolation and reproduction of high-titer HFRSV, and has been used to study the virulence of strains from different sources, determine the efficacy and safety of vaccines, screen antiviral drugs, and study HV infection The pathogenesis and so on.

　　(3) Comparative medicine The model animals began to show symptoms such as thinness, fluffing, spasms, convulsions, stiff tails, and paralysis of hind limbs 7-8 days after being infected with the virus, and began to die. The animal model of HV infection in suckling mice is dominant infection or even death, accompanied by obvious pathological changes. The rabbit, rat and gerbil models were subclinical infections, and there were no obvious pathological changes. The clinical symptoms and pathological changes of the suckling mouse model are basically similar to those of patients with epidemic hemorrhagic fever. The onset time of model animals is related to the route and dose of virus inoculation. Intracranial, abdominal, intramuscular and subcutaneous inoculation can cause infection. There is no significant difference between intracranial and intraperitoneal vaccination and simple intracranial vaccination in the time of onset and antigen distribution. However, the onset of intraperitoneal inoculation of suckling mice was 4 to 5 days later than that of combined brain-abdominal vaccination and intracerebral vaccination alone.