动物造模,药效评价 z-bio 2024-09-23 299

　　The fecal roundworm is the only worm that has both complete free living and parasitic generations. Fecal roundworm disease is a common parasitic disease in tropical and subtropical regions. Mild infection with inconspicuous clinical symptoms, but when patients suffer from malnutrition, poor resistance, immunodeficiency, or receive immunosuppressive therapy, it can often cause recurrent self infection of fecal roundworms, leading to patient death. In China, He Dengxian et al. conducted parasitic, pathological, and clinical observations on fecal roundworm disease in young dogs infected with fecal roundworm under immunosuppressive conditions. They believed that the severe fecal roundworm disease in this model animal had similar parasitic, pathological, and clinical manifestations to severe human fecal roundworm disease, and established a laboratory model of explosive fecal roundworm disease infection. In foreign countries, Schad GA, Genta RM, and others have conducted research on severe fecal roundworm infection induced by immune treatment of dogs infected with human fecal roundworm; Nolan TJ et al. conducted a study on the simple and severe infection of fecal roundworm disease in long clawed sand mice, and found that steroid treated sand mice infected with fecal roundworm can cause fatal severe infection. However, long-term treatment with low-dose steroids or a dose of 2mg at longer intervals can induce self infection of fecal roundworm in sand mice without developing into severe infection, forming a chronic infection experimental animal model.

　　(1) Method of replication: ① Take fresh feces from patients and place them at 28-30 ℃ for 48 hours to allow rod-shaped larvae to develop into filamentous larvae. ② Separate filamentous larvae using the Bayesian method, rinse with physiological saline, and count Select healthy puppies and inoculate 500-1000 filamentous larvae subcutaneously through the abdomen After vaccination, check the animal feces daily. After the presence of larvae in the feces, administer a daily dose of 5mg/kg body weight of prednisone to the puppy for immunosuppression for one week The cage for raising puppies should be kept at a certain distance from the ground to prevent animals from coming into contact with feces on the ground and avoid repeated infections.

　　(2) Model characteristics: After 2 weeks of animal infection, the amount of cysticercosis significantly increased, and diarrhea appeared after the appearance of cysticercosis in feces. After 2 weeks of immune treatment, diarrhea worsened, causing dehydration, emaciation, and exhaustion in animals, as well as bloody feces and respiratory distress leading to death. The pathological changes of ulcerative colitis, colitis, pneumonia, and pulmonary hemorrhage in the model replicated by this method are very similar to the pathological changes of the intestine and lungs during severe fecal nematode infection in humans. Severe enteritis, pneumonia, pulmonary hemorrhage, and sepsis caused by immunosuppressive treatment of puppies infected with fecal roundworm are the main causes of death in puppies, similar to the causes 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 immunosuppressants in clinical practice.

　　(3) If puppies infected with roundworms using the above method in comparative medicine do not receive strong pine immunization treatment, their parasite excretion will be higher in the first month of infection, and will significantly decrease by the second month, showing a low infection state that can last for more than 4 months, and can be used as a normal process of fecal roundworm infection in dogs. Puppies infected with fecal roundworms and then immunized with prednisone can die from severe illness within 18-20 days. The animal model replicated by this method, due to its parasitic and 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.