(1) Replication method: female Hartley guinea pigs were used. Mycobacterium tuberculosis in the middle logarithmic growth period was diluted to the required inoculation concentration with sterilized double distilled water. The compartment of the spray was filled with 5ml of distilled water containing bacteria in the air transmission device, and 20~50 bacteria were given to each guinea pig. After infecting guinea pigs with Mycobacterium tuberculosis, the body responds to the bacterium, causing tissue damage. In the early stages of infection, small, discontinuous aggregates of epithelial macrophages and granulocytes containing eosinophilic particles deposit in the parenchymal tissue near the trachea and blood vessels of the lungs, leading to inflammation; Then the diameter of the injury increases and more and more granulomatous lymphadenitis forms; Later developed into typical granulomas; In the late stage of granulomas, multiple granulomas form dense inflammatory zones, alveolar structures disappear, typical calcifications form in necrotic centers, and pulmonary fibrosis occurs in the middle and late stages of infection. It can cause death in guinea pigs 100-140 days after infection.
(2) The severity and survival time of animal infections caused by different infection routes and vaccination doses vary. Guinea pigs can survive for 4-8 weeks after intraperitoneal injection of 2 × 1000000 Mycobacterium tuberculosis. This model uses a small amount of Mycobacterium tuberculosis aerosol to infect guinea pigs, causing chronic infection of pulmonary tuberculosis and replicating symptoms similar to human tuberculosis infection. Three months before infection with tuberculosis bacteria, guinea pigs develop progressive lung lesions due to cell-mediated immune responses and delayed hypersensitivity reactions to the bacteria. They then enter a chronic infection phase, exhibiting typical symptoms of chronic tuberculosis such as granulomas and pulmonary fibrosis, and have a longer survival time.
(3) Guinea pigs in comparative medicine are sensitive to pulmonary tuberculosis bacteria, and can replicate a guinea pig model of Mycobacterium tuberculosis disease by infecting them with aerosols of only 20-50 bacteria. The infection pathway is the same as the natural human infection pathway, and chronic infection symptoms, cheese like lesions, and symptoms similar to human infection with Mycobacterium tuberculosis appear. Therefore, guinea pigs have excellent applications in the study of the pathogen, disease progression, immunology, and vaccine evaluation of Mycobacterium tuberculosis. However, it is difficult to control the bacterial infection caused by aerosols, and the operation is challenging, requiring the provision of relevant instruments. The only drawback of using guinea pigs as animal models is the lack of immunological reagents, which makes it difficult to qualitatively and quantitatively identify cytokines and cell subtypes related to immune responses.