动物模型,实验室 z-bo 2020-07-23 607

      Recently, in the fight against the global pandemic, exciting innovations have inspired the world, and the world has successfully established a new coronavirus animal model! The mission of the Institute of Animal Science of the Chinese Academy of Medical Sciences/Peking Union Medical College is to scientifically and effectively develop rhesus monkeys and humanized receptor hACE2 transgenic mouse models, which will bring comprehensive drug discovery in China. Screening and vaccine evaluation are now available. The preamble of the World Health Organization is called Model Development and Application Model.

　　 First discuss animal models of infectious diseases. As the name implies, the animal model of infectious disease refers to the infection of a specific laboratory animal with the pathogen of the infectious disease, or the genetic material of the pathogen artificially introduced, so that the animal has the same disease as the patient. It has similar disease changes and is used for disease through comparative medical analysis. Animals with anthropomorphic capabilities have been developed, screened and evaluated for mechanism research, anti-pathogen drugs and vaccines. In short, scientists do their best to treat experimental animals that have the same disease as the patient. Only in this way can they replace humans and conduct various medical experiments. Therefore, animal models are often referred to as "patients" in the laboratory.

　　 But it is not easy to make animals suffer from the same diseases as humans! For example, hepatitis B virus, which seriously threatens people's health, has not yet been able to find a suitable animal as a model.

　　 Why? Infections are caused by specific pathogens that cause diseases, including viruses, bacteria, parasites and other microorganisms that infect the human body. Therefore, in the study of animal models, what is important is the pathogenicity of pathogens to animals, that is, whether animals can be infected by pathogens to replicate and simulate all or some of the characteristics of the disease. Generally speaking, pathogens evolve simultaneously with host animals. Therefore, the two have formed a relationship of interdependence, coexistence and exclusion. This relationship of interdependence, coexistence and elimination is manifested in symbiosis, physical damage (disease) and insurvivable pathogens such as parasite infections, organs and tissues, depending on the species and biological characteristics. It is divided into infectious diseases (including blood) and intracellular infections. Therefore, the mechanism of infection is different, and the specific selection requirements for the infected animal host are also different. Generally, parasites, bacteria, viruses, and especially viral pathogens are more specific. Infections usually enter cells through specific receptors, and the evolution of receptors in different animals may not be close to similar animal species. Therefore, it introduces uncertainty and complexity in the preparation of animal models. This is one of the reasons why certain pathogens do not have ideal animal models. At the same time, due to the similarities and differences in the genetic composition and biological characteristics of various animals, it is possible to use animals with farther genetic distances as models of infectious diseases. Therefore, the study of infectious animal models, especially the pathogens of new infectious diseases, faces the first problem of animal infectivity, or the susceptibility of animals that are often tested, compared and screened by many different types of animals. Do it. , In order to develop a more ideal model.

　　 Next, how do you determine the ideal or successful animal model?

　　 First, we need to prove that pathogens can replicate in animals. Therefore, in order to prove the replication of pathogens in the body, we need to detect live diseases in infected animals. The most effective method is to isolate the virus from the animal within a certain period of time after inoculation. Nucleic acid is usually obtained by virus culture rather than PCR detection. Simultaneously with virus isolation, detection of nucleic acid content and duration by PCR is usually an important indicator of model judgment. Second, the model animal should show histopathological changes very similar to the patient. The pathological changes of a specific disease are the basis for the onset and development of the disease, as well as the origin of the game between the pathogen and the body. Specific damage to various tissues (especially target organs) is a key indicator for model judgment. Again, we need to prove that pathogens can cause specific immune responses in the body. Specific antibodies are usually detected within 10 days after infection, increase within 2 weeks, and reach a peak within 3-4 weeks. The detection of neutralizing antibodies is very important and is a basic indicator of model application evaluation. The detection of cellular immunity and inflammatory factors is also an important indicator of judgment.

　　 Finally, I emphasize that clinical symptoms, hematological changes, blood biochemical changes, imaging examinations, etc. are all based on the objective standards of the above three indicators. Appropriate comparative medical analysis should be carried out to establish mutual confirmation system indicators. Only display data.