动物造模,传染病动物模型 z-bio 2021-04-02 1270

　　An ideal infectious disease animal model should completely or basically resemble the clinical manifestations, disease process, pathophysiological changes, immunological response and other disease characteristics of human diseases. However, due to the species differences between animals and humans, the same disease pathogen may have different manifestations when infecting different animals. In other words, it may be close to the manifestations of human diseases in some aspects, but in some aspects it is not obvious or does not show human characteristics. Therefore, it is often necessary to establish multiple animal models for the same pathogen. In other words, it is necessary to select multiple animal models to fully understand the characteristics of infectious diseases. At the same time, the focus of research is different, and animal models should be selected specifically. For example, there are many types of highly pathogenic avian influenza (H5N1) animal models, including ferrets, non-human primates, and various rodent models. The ferret model is very similar to the patient’s clinical symptoms, respiratory virus distribution, and lung disease characteristics, and is suitable for studying the corresponding symptom mechanism of humans; the immune response of the primate model is similar to that of humans, and the immune function can be focused on; the rat and Brandt's vole model It is very similar to recessive infection, which can be used to understand the relationship between infection and disease; the mouse model shows the dose-dependent relationship between disease and infected virus, and can be used to study the death mechanism of critically ill patients. Therefore, according to the different characteristics of the model, model selection in multiple fields such as pathogenesis, influenza virus transmission, virus mutation, and natural host carrying should be carried out.

　　The selection and application of infectious disease animal models are very wide. For example, it plays a vital role in the study of pathogen characteristics, pathogenic mechanisms, pathological changes, immune responses and other aspects. Stable and specific animal models also play an irreplaceable role in drug screening, biologics, vaccine development, and effect evaluation. In summary, the selection and application of pathogenic animal models mainly include the following aspects:

　　1. Choice of disease process model of infectious disease

　　Different infectious diseases have different disease processes, and basically have the characteristics of incubation period, early onset, duration and recovery period. If the goal is to study the whole process of the disease, the ideal method is to simulate the natural infection mode, with a small dose of pathogen, multiple times, and to infect animals through the natural infection route to prepare a model. If a large dose is used for infection via intravenous and other means, the animal will not directly develop the disease after the incubation period, and it is impossible to study the interaction between the pathogen and the body during the incubation period.

　　2. Model selection of infectious disease transmission route

　　Infectious diseases have different transmission routes, and animal models can be used to confirm the natural transmission route and study the mechanism. According to different transmission routes of infectious diseases, animals can be infected through unnatural routes, and pathogenicity differences of pathogens can be studied. Multiple infections at the same time can comprehensively understand the interaction between the pathogen and the body. Research on the transmission mechanism of pathogens of emerging infectious diseases and mutual infection of different animals can be used to design and prepare models for different transmission routes.

　　Three, pathogen infection dose model selection

　　Some infectious diseases have dose-dependent infection characteristics, and a series of different pathogen concentrations can be carried out to infect animals to determine the best infectious dose. Different infection routes have different dosages, and special attention should be paid to the relationship between them. Especially when using animal models to evaluate drugs, biological preparations and vaccines, the use of doses is directly related to the results of effect evaluation.

　　4. Selection of animal models for clinical research

　　Infectious diseases are often diagnosed by clinical at first. Therefore, the clinical symptoms of animal models are very important, especially the discovery of characteristic disease manifestations, which is very important for early disease diagnosis.

　　5. Selection of pathogenic models of infectious diseases

　　At present, one of the most important purposes in the preparation of models is to study the etiology of infectious diseases. Especially for viral pathogens, the pathogenicity of no viral pathogen is very clear. One is that the pathogen itself is very complex and can be said to be in a dynamic state. On the other hand, it is different cells from different sources. There are differences in pathogens caused by tissues and organisms, and only through the accumulation of a large number of animal models, further studies to clarify the nature of the pathogen.

　　6. Selection of immunological models for infectious diseases

　　The individual occurrence of infectious diseases, the final result is the interaction between the pathogen and the body. There may be several manifestations: no disease or hidden infection; disease occurs and the body recovers; the body dies after the disease occurs. But no matter which form, the body's immune system will definitely respond. It can also be said that the result of the body's immune response leads to the manifestations of different diseases. The humoral and cellular immunity caused by different pathogens are also different, and the specific immunity and non-specific immunity are also different. The application of animal models can clarify many problems in immunology.

　　Seven. Pathophysiology model selection of infectious diseases

　　Animal models can reflect the pathophysiological changes of the disease to varying degrees, especially the discovery of characteristic pathophysiological dynamic changes. It is useful for understanding the pathogenic mechanism of pathogens, the damage of body cells, tissues and organs, and the intervention of different types of immune cells. There is no substitute for it.

　　8. Genetic model selection

　　The main factors for the occurrence of body diseases include genetic and environmental influences. Different types of diseases have different degrees of influence from genetic and environmental factors. Infectious diseases are definitely caused by pathogens, but why pathogens infect the body, especially viral pathogens, animal species, receptor structure, etc., all affect the disease, although a lot of basic research has been carried out in all aspects, animals are infected with pathogenic microorganisms and The exact genetic mechanism of the parasite is still unclear. In addition, pathogens are in different animals. In order to adapt to the body's resistance, they will self-adjust and mutate. The body will also make new corresponding changes. This requires the control of genetic mechanisms and is the direction of research.

　　Nine, different animal sensitivity analysis model selection

　　Some animals are infected with a certain pathogen, some animals are not infected by recessive infection, some animals only carry the pathogen, and some animals are not infected at all. In a sense, these situations are different types of animal models, which can be understood. For disease models and disease resistance models, why do these situations occur? Which genes of the body are involved in the disease process? What are the genetic mechanisms? They are all key research objects.

　　10. Choice of communication model

　　For infectious diseases, the mode of transmission is very critical, and model research is also very difficult, such as cross-species transmission between animals and changes in transmission intensity.

　　11. Comparative medical model selection

　　Animal models provide different degrees of disease mimicry studies. Although there may be cases where the pathogen completely replicates the disease, it is after all the performance of the animal body. After all, animals and humans are different in many aspects such as genetic makeup. Therefore, the pathogen is in the body. Survival conditions, the body's mechanism of processing pathogens, etc., are definitely not exactly the same, which are the same, which are different, and why? Only through comparative studies of different aspects and different levels can we get closer to understanding the nature of disease.

　　12. Blood and biochemical model selection

　　Pathogens cause diseases and can cause reactions in different organs of the body. Some cellular reactions will be detected in the blood. Therefore, through dynamic monitoring of changes in organ function indicators, such as enzymes, we can understand the role and damage of different organs in the course of the disease. Degree, combined with changes in pathophysiology, to understand the degree of damage to the body caused by disease.

　　13. Drug and vaccine model selection

　　One of the most important purposes of

　　 model development is its application in drug and vaccine research and development. The effectiveness research of drugs and vaccines relies on the objectivity and scientificity of animal models. The comparative research results of pathogenic, pathological, immune, biochemical, clinical and other detection and evaluation indicators determined by model animals provide judgments for the effectiveness of drugs and vaccines. The objectivity of the model is not accurate, and the evaluation results will be different. Another important aspect of using models to study the effects of drugs and vaccines is the mechanism through which drugs and vaccines work, what changes have been made to the body and pathogens under the action of drugs and vaccines, and how these changes affect the body and pathogens. And so on, all need targeted research.

　　14. Life science model selection

　　Infectious disease pathogens act on the body to cause disease. It can be said to be a comprehensive manifestation of the interaction between two living organisms. Therefore, all changes that can be observed and detected, including the organism and pathogens, are clues to the disease and should be sufficient. the study. Therefore, as an animal model, it should be a very complex and systematic system. Any research on it will be very important for life science research, in a sense, the study of diseases and the special life performance of the body. After being clear, we will also be more aware of life itself. This is also the infinitely challenging feature of pathogenic infectious disease animal models. It is also the entry point and breakthrough point of our detailed research, and it is also the most important part of life research.