动物造模,药效评价 z-bio 2024-07-02 398

　　The fecal roundworm is the only worm that has both a complete free living generation and a parasitic generation. Fecal roundworm disease is a common parasitic disease in tropical and subtropical regions. Mild infection with mild clinical symptoms, but when patients suffer from malnutrition, poor immunity, immunodeficiency, or receive immunosuppressive treatment, it can often cause outbreaks of self repeated infection of fecal roundworms, leading to patient death. In China, He Dengxian and others conducted parasitological, pathological, and clinical observations on fecal roundworm disease in young dogs after being infected with fecal roundworm under immunosuppression. They believed that the severe fecal roundworm disease in this model animal had similar parasitological, pathological, and clinical manifestations to severe human fecal roundworm disease, and established a laboratory model for outbreak of fecal roundworm disease infection. Abroad, Schad GA, Genta RM, and others have conducted research on severe fecal roundworm infection induced by immune treatment after human fecal roundworm infection in dogs; Nolan TJ et al. conducted a study on simple and severe infection with fecal roundworm disease using long clawed gerbils and found that steroid treated gerbils infected with fecal roundworm can cause lethal severe infection. However, long-term treatment with low doses of steroids or long-term treatment with a dose of 2mg at longer intervals can induce gerbils to self infect with fecal roundworm disease without developing into severe infection, in order to form an experimental animal model of chronic infection.

　　(1) Reproduction method: ① Take fresh feces from patients and place them at 28-30 ℃ for 48 hours to develop filamentous larvae. ② Separate filamentous larvae using the Bayesian method, wash them with physiological saline, and count them Select healthy young dogs and subcutaneously inoculate 500-1000 filamentous larvae per dog through the abdomen. ④ After vaccination, animal feces should be checked daily. One week after the feces show larvae, puppies should be given an oral dose of 5mg/kg prednisone per day for immunosuppression The cage for keeping young dogs should be kept at a certain distance from the ground to prevent contact between animals and feces on the ground, and to avoid repeated infections.

　　(2) Model characteristics: After 2 weeks of animal infection, the amount of larvae excreted significantly increased, and diarrhea appeared after the appearance of larvae in feces. After 2 weeks of immune treatment, diarrhea worsened, causing dehydration, emaciation, and exhaustion of the animals, as well as bloody feces and respiratory distress leading to death. The pathological changes of the model replicated by this method, such as ulcerative colitis, colitis, pneumonia, and pulmonary hemorrhage, are very similar to the pathological changes of the intestine and lungs in humans infected with severe fecal roundworm disease. The main causes of death in young dogs are severe enteritis, pneumonia, pulmonary hemorrhage, and sepsis caused by immunosuppressive treatment after being infected with fecal roundworm, which is similar to the cause of death from severe fecal roundworm infection in humans. Infected puppies can cause secondary bacterial infections and sepsis after immunosuppression, similar to severe fecal roundworm disease patients treated with adrenaline and other immunosuppressive agents in clinical practice.

　　(3) If puppies infected with roundworms using the above methods are not treated with prednisone immunity in comparative medicine, their larval discharge is higher in the first month of infection, but significantly decreases in the second month, presenting a low-grade infection state that can last for more than 4 months. This can be used as a normal infection process for fecal roundworms in dogs. Puppies infected with fecal roundworms and then immunized with prednisone can die of severe illness within 18-20 days. The animal model replicated by this method, due to its parasitological, pathological examination results and clinical manifestations, is very similar to severe human fecal roundworm disease in clinical practice, and can be used for experimental model research on human outbreak of fecal roundworm disease infection.