动物造模,药效评价 z-bio 2024-09-06 540

　　Pneumocystis carinii is an important opportunistic parasitic infection that can cause fatal pneumonia in immunocompromised patients. The species of Pneumocystis that parasitize different mammals are different. The species that infects humans is Pj, while those that infect rodents are Pc. Diseases caused by different types of Pneumocystis are referred to as PCP. Due to the lack of a reliable and stable in vitro culture system for Pneumocystis carinii and the atypical clinical manifestations of PCP, animal models remain an ideal research tool to date. In addition to commonly used rats and mice, there are also hamsters, guinea pigs, nude mice, pigs, dogs, monkeys, and rabbits used for membrane making. Since the 1950s, many scholars at home and abroad have started studying animal models of PCP, mainly using immunosuppressants to induce disease in animals. The most commonly used method currently is to establish a PCP animal model using immunosuppressants, antibiotics, and low protein foods. In China, from the mid-1980s to the early 1990s, Yuan Jiyun, Tang Xueheng, He Xiancheng, and others successfully established a rat model of Pneumocystis carinii using immunosuppressants; Zhou Liping et al. successfully established an animal model of the disease using endotracheal injection method. Afterwards, An Chunli and others induced PCP in Wistar rats by subcutaneous injection of dexamethasone after ether anesthesia, and adding oxytetracycline to drinking water. PCP was induced after 6 weeks of medication, and all rats were successfully induced after 8 weeks; Guo E and others induced PCP in KM mice by subcutaneous injection of cortisone acetate and addition of tetracycline to drinking water. After 5 weeks of medication, the parasite was detected, and after 8 weeks, most animals were able to detect the parasite; In the future, many scholars have successfully induced PCP using methods such as "immunosuppressants plus antibiotics" or "immunosuppressants plus antibiotics and low protein foods". However, the main drawback of these models is that animals die in large numbers due to severe infections or failure to reduce or stop medication after animal onset, leading to the inability of animal models to sustain for a long time. Tong Xiaoying and others reduced the mortality rate of animal models by providing high protein food to rats; Ni Xiaoyi et al. induced PCP by administering immunosuppressants, increased intratracheal inoculation of Pneumocystis carinii cysts (frozen), and antibiotics, which resulted in infection in most rats in the fourth week without the detection of secondary infections caused by other pathogens; Chen Dianxue et al. established a PCP animal model by halving the induction dose, and there was no significant difference in infection rate, but it could reduce animal mortality; Zhang Fan et al. induced PCP in SD rats and ICR mice by subcutaneously injecting dexamethasone into the groin and adding tetracycline hydrochloride to their drinking water. As the body weight decreased, the dosage also decreased, that is, by administering according to the actual body weight. This avoided excessive immune decline in the animals and achieved a 100% survival rate, with an infection rate of 76.7%. beyond seas. Weller was the first to inject cortisone into rats to prevent bacterial infection and induce PCP. The PCP model he established laid the foundation for later research. Mcfadden et al. induced a mouse PCP model using anti-CD4 monoclonal antibodies; Many scholars such as Farrow and Walzer have also conducted research on PCP models.

　　(1) The replication method involves SD rats weighing 200-250g or ICR mice weighing 25-30g. Inject dexamethasone injection subcutaneously into the groin of animals at a dose of 0.02mg/g body weight, twice a week for a total of 11 weeks. At the same time, all animals were free to drink cold boiled water containing 1mg/ml tetracycline hydrochloride. Each dose is administered based on actual body weight.

　　(2) Typical interstitial pneumonia can be observed in lung tissue slices of model mice, and PC cysts can be observed in lung imprints. Although the dosage was reduced with the decrease of animal body weight to avoid excessive immune decline and ensure animal survival, it also resulted in a decrease in the number of infected animals.

　　(3) There are significant differences in the toxic reactions caused by the use of immunosuppressive drugs among animals of different lineages in comparative medicine; The degree of infection induced by the same modeling method is related to the animal species; The dosage directly affects the infection and mortality rates of animals; The time it takes to locate the insect body may vary depending on the method of modeling. This model can be used for pathogenic and pathological studies of human cases, as well as for research in immunology, epidemiology, diagnosis, and efficacy evaluation.