动物模型,真菌感染 z-bo 2020-08-04 672

　　Deep fungi are often inhaled through the respiratory tract or invaded and infected through skin trauma. The lesions spread from the local to the system, involving more complex interactions between microorganisms and the host. The efficacy, pharmacokinetics, and toxicological evaluation of systemic drug delivery against deep fungal infections Many places rely on whole animals and animal models. Due to different fungal species, infection methods and host response, the requirements for animal models are also different.

　　【Modeling mechanism】Usually, the infected strains are Candida, Cryptococcus, Sporothrix, Color fungus, Aspergillus and Penicillium. The source of the strain and the prior in vitro test are the same as those of the superficial fungal infection. The amount of fungal infection and the amount of treatment administered to animals should also be determined in advance. Generally, mice are mainly used for deep fungal systemic infection experiments, and the suspension of infectious bacteria that can cause 95% of experimental animals to die through intraperitoneal or intravenous injection. It is usually administered immediately or 6 hours after infection. The route of administration is oral, intravenous or subcutaneous injection. The reaction of animals can be observed continuously for 7 days, and the number of animal deaths can be recorded. The efficacy is indicated by the protection rate of the drug on animals.

　　It has been reported that histoplasma infection is closely related to host cell-mediated immune response. Therefore, intraperitoneal injection of the bacteria in nude mice can quickly develop into a lethal dissemination model characterized by reticuloendothelial tissue infection. In addition to the relationship between host immune factors and infection, the relationship between infected animals and drugs also needs to be considered. For example, for azole drugs metabolized by cytochrome P450, mice with higher cytochrome P450 metabolic activity are not easy to achieve effective antifungal concentration in the body. Guinea pigs whose enzyme activity is similar to that of humans can be selected. Injecting immunosuppressive agents to cause guinea pigs to be infected with the deep-pathogenic Candida krusei after the immunosuppression state can be used to establish a corresponding efficacy evaluation model. Cryptococcal infection can be inoculated intravenously in mouse lung models, and guinea pigs, rats and rabbits can also be inoculated intraperitoneally.

　　[Model features] It is suitable for general deep fungal infection research, and can further improve the model based on the host immune response, the relationship between infection and the host, and the relationship between the host and the drug. A few deep fungal system infection models need to be further studied and improved.

　　[Model evaluation and application] It is mainly used for the evaluation of the efficacy of anti-deep fungal drugs and the research of infection immunity. The design of the model takes into account the pathological mechanism of clinical deep fungal infection or the mechanism of drug action, so it has a good predictive value.