动物造模,药效评价,结核病模型 z-bio 2024-07-24 424

　　Guinea pigs are highly sensitive to Mycobacterium tuberculosis, and the pathological changes after infection are similar to those of human beings. Therefore, guinea pig tuberculosis models have been widely used, and different model preparation methods have also been developed.

　　1. Aerosol infection model Aerosol infection is the most commonly used method to establish guinea pig tuberculosis model. Guinea pigs are highly sensitive to Mycobacterium tuberculosis, and respiratory infection with several cfu of tuberculosis bacteria can lead to the occurrence of progressive pulmonary tuberculosis. Using an aerosol generator, guinea pigs were infected with 20-30 strains of Mycobacterium tuberculosis. About 3 weeks after infection, lung lesions appeared with necrosis of the lesion center, and tuberculosis bacteria were detected in the lungs and lymph nodes. Subsequently, the bacterial load in the lungs continued to increase to 100000 to 1000000 cfu. After 30 days of infection, typical granulomas appeared with obvious central necrosis, surrounded by lymphocytes, macrophages, and multinucleated giant cells. Afterwards, the lesion further worsened and multi-level granulomas appeared. This low-dose aerosol infection model is widely used in the evaluation of anti tuberculosis vaccines and compounds.

　　2. Subcutaneous injection of Mycobacterium tuberculosis into the groin of the hind limbs of guinea pigs infected with tuberculosis model is also a commonly used method to prepare tuberculosis models in guinea pigs. 500 cfu of Mycobacterium tuberculosis sensitive strain is injected into guinea pigs to infect them. After 2 weeks, PPD and ESAT-6 skin tests are carried out once a week. Two weeks later, the ESAT-6 skin test, and three weeks later, both PPD and ESAT-6 skin tests were positive.

　　3. Guinea pig tuberculosis model with latent infection of guinea pigs has been widely used. Because guinea pigs are highly sensitive to Mycobacterium tuberculosis, there are few reports on guinea pig models with latent infection of tuberculosis, and there are also some successful reports in recent years. 500 cfu of H37Rv strain with restored virulence was injected subcutaneously into the groin of guinea pigs to challenge the virus. Two weeks after challenge, isoniazid (10mg/kg) and pyrazinamide (40mg/kg) were administered orally three times a week to control MTB proliferation. The drug was discontinued at 4, 8, and 12 weeks, respectively. The natural recurrence of tuberculosis was observed after drug withdrawal in the 4-week group, and the natural recurrence and dexamethasone induced recurrence of tuberculosis were observed after drug withdrawal in the week group and the 12 week group. Results In the 4 week group, tuberculosis recurred naturally after drug withdrawal; In the 8-week group, tuberculosis recurred naturally and was induced by dexamethasone; There was no natural recurrence of tuberculosis in the 12 week group, but dexamethasone could induce the recurrence of tuberculosis. The results showed that the combination of isoniazid and pyrazinamide chemotherapy could inhibit MTB proliferation and successfully establish a latent MTB infection model in guinea pigs.