动物造模,药效评价,SARS感染 z-bio 2024-08-21 408

　　(1) Healthy rhesus monkeys and crab eating monkeys aged 3 to 6 years old were replicated by intramuscular injection of Simvastatin anesthesia at a dose of 0.15ml/kg body weight, followed by intranasal and tracheal infection with SARS CoV BJ01 strain (10 ^ 5.7 TCID50/ml). The virus was isolated from throat swabs of model animals on the 2nd, 5th, and 7th day after infection, and was identified as SARS virus by immunofluorescence. Some infected monkeys have bleeding spots or patches in their lungs. All infected monkeys can present with varying degrees of multifocal monocyte interstitial pneumonia, characterized by widened alveolar septa, bleeding, exudation, shedding of alveolar epithelial cells and macrophages in the alveolar cavity, and shedding of epithelial cells in the bronchioles and bronchioles; A small amount of inflammatory cells, mainly lymphocytes, infiltrate into some alveolar septa, and a transparent membrane is occasionally formed in the alveolar cavity. Immunohistochemistry can detect SARS virus antigen in alveolar macrophages and type I epithelial cells. In the autopsy of infected animals, viral RNA can be detected in both bronchial lymph nodes and myocardium, and there are inflammatory changes. Most model animals exhibit multifocal lymphocytic hepatitis with occasional hepatocyte necrosis.

　　(2) The model features pathological changes after animal infection. The lungs are the main target organ of viral infection, and diffuse alveolar damage can be seen in all lung lobes, forming a transparent membrane and infiltrating monocytes. SARS virus RNA can be detected in tissue samples such as blood, throat swabs, alveolar epithelial cells, and bronchial lymph nodes of model animals through virological testing and immunological methods, indicating that the virus can replicate in non primate animals; And the humoral and cellular immune responses of the organism. The number of white blood cells and platelets in partially infected monkeys showed a transient decrease from the third day of infection and gradually returned to normal levels; Animals produce specific antibodies against SARS virus, and the levels of serum anti SARS CoV specific antibodies are relatively high at 2, 3, and 4 weeks after infection. From this, it can be seen that rhesus monkeys can serve as an animal model for SARS virus infection, suitable for research on the pathogenesis, drug screening, and vaccine evaluation of SARS.

　　(3) No typical clinical symptoms of SARS, such as high fever, dry cough, drowsiness, transient rash, and difficulty breathing, were observed in all infected monkeys in comparative medicine. Two thirds of rhesus monkeys showed transient low-grade fever; And the body temperature of all crab eating monkeys fluctuates within the normal range. However, the pathological changes in the lung tissue of infected monkeys, such as diffuse alveolar injury and monocyte infiltration, are similar to those in human lung tissue after infection with SARS coronavirus, and the pathological changes are milder than those in humans. After infection, model animals can produce SARS specific antibodies in their bodies. Around 4 weeks after infection, the antibody levels in their serum are higher, which is similar to that of human SARS patients; The specific IgM antibodies produced in SARS patients' bodies appear from day 7 and reach their peak on day 11; IgG antibodies are produced after 10 days and reach their peak at 20 days; Simultaneously, the virus was isolated from the tissues and secretions of infected monkeys. In summary, the pathological changes in rhesus monkeys infected with SARS virus are very similar to those in humans infected with SARS virus, and non-human primates have a genetic background similar to humans, making them an ideal animal model for SARS. However, due to objective limitations, monkeys cannot be used in large-scale studies, which reduces the application value of this model.