动物造模,人类疾病动物模型 z-bio 2021-05-24 531

　　1. Characteristics of animal models of human diseases

　　The ultimate goal of establishing a disease model is to prevent and treat human diseases. Therefore, the reliability of the research results of the disease model depends on the similarity or equivalence between the model and the human disease. A good disease model needs to have the following characteristics: (1) It must be able to replicate the human disease to be studied, and the performance of animal disease should be similar to that of human disease. (2) Since animals can reproduce diseases, it is best to divide diseases into two parts to reproduce diseases. Animals; ③Animal background information must be complete, qualified for laboratory animals, and the life cycle must meet the needs of the experiment; ④Animals must be cheap, purchaseable and easy to transport; ⑤Use as many small animals as possible. If the replication rate is not high, then animal models of human diseases will not be of high value. If one method can be used to replicate multiple models without specificity, the value of the model will also decrease. It should be emphasized that no animal model can replicate all the symptoms of human disease. After all, animals are not humans. The model experiment is only an indirect study of the expansion method, and in some aspects or some aspects may only resemble human diseases. Therefore, the correctness of the model experiment conclusions is relative and must be verified by the human body. When something different from human disease occurs during the replication process, it is necessary to analyze the nature and degree of the difference, find similarities in common, and correctly evaluate its value. Therefore, successful animal disease models often rely on careful initial design.

　　2. Principles of establishing animal models of human diseases

　　How to build animal models is often considered in the design of biomedical scientific research. This is because many experiments to determine disease and treatment effects cannot or should not be performed on patients. .. Generally, it depends on the copy of the animal model, but it should be carefully designed and the following principles should be followed during the design process:

　　(1) Similarity

　　The purpose of copying animal human disease models is to find out which model can be inferred. Relevant laws apply to patients. Extrapolation is a risk, because animals and humans are not an organism. For example, a drug that is ineffective in animals does not mean that it is clinically ineffective, and vice versa. Therefore, the important principle for designing animal disease models is to make the replicated models as close to human diseases as possible. Of course, it is best to find the same spontaneous animal diseases as human diseases. For example, the rat essential hypertension discovered by Japanese scientists is an ideal model for studying human essential hypertension. Spontaneous coronary atherosclerosis in pigs is an ideal model for studying human coronary heart disease. This is also the ideal model. After all, animal spontaneous disease models that are the same as humans are rare and usually require artificial replication. In order to resemble human diseases as much as possible, we must first pay attention to the choice of animals. For example, rabbits are a model of hyperlipidemia because their plasma triglyceride, cholesterol and free fatty acid levels are very similar to humans, and their low-density and very low-density lipoprotein components are also similar to humans, so they are suitable . Secondly, in order to make the model as human as possible, in fact, the modeling method should be continuously improved. For example, ligating the appendix blood vessels of a rabbit can cause appendix necrosis and perforation, which can lead to peritonitis, which is different from acute obstructive appendicitis in people with perforation and peritonitis. The initial blood supply can lead to perforation of the appendix, and peritonitis is similar to a human condition, so it is an ideal method. If the animal model does not match the clinical situation, an effective animal treatment plan may not always be used in the clinic. vice versa. For example, animal endotoxin shock (endotoxic shock refers to shock caused by intravenous injection of bacteria and their toxins into animals) is not exactly the same as clinical septic (septic) shock (septic shock). Endotoxic shock in animals is ineffective. It has long been adopted by clinicians. At present, some people have been modified to inject bacteria into the gallbladder of animals with ligated gallbladder artery and bile duct, thereby replicating a model of human septic shock. The animal is believed to have infection and endotoxin poisoning and clinical septic shock.

　　A series of checks are required to determine whether the copied model resembles a human being. For example, someone checked the arterial pressure, pulse rate, venous pressure, respiratory rate, arterial blood pH, arterial partial pressure of oxygen and carbon dioxide, venous blood lactic acid concentration and blood volume caused by quantitative blood sampling. I found this situation. The shock model is very similar to clinical hemorrhagic shock. Therefore, the hemorrhagic shock model reproduced by this method is considered an ideal model. Similarly, when rhubarb is used in mice according to the theory of Chinese herbal medicine, it looks like human "spleen deficiency syndrome". If you use Sijunzi to cure according to the theory of Chinese herbal medicine, you can regard it as an animal model of "spleen deficiency syndrome".

　　(2) Reproducibility

　　The ideal animal model must be reproducible or standardized. For example, quantitative bloodletting can lead to 100% hemorrhagic shock and 100% mortality, which meets repeatability and standardization requirements. Another example is the use of dogs as a model of myocardial infarction. This is because its coronary circulation is similar to that of humans, and it is most suitable for thoracotomy that exposes the heart of laboratory animals. However, the result of ligating the coronary artery is that the results of ligating the same part of the same artery in dogs are very inconsistent, unpredictable, and impossible to standardize. In contrast, the results of coronary artery ligation in rats, mice, hamsters, and guinea pigs are relatively stable, consistent, predictable, and therefore can be standardized. To improve

　　The reproducibility of animal model replication needs to be consistent in the following aspects: animal breed, ancestry, age, sex, weight, health status, feeding management, experimental and environmental conditions, season:, circadian rhythm, pressure, room temperature, Humidity, air pressure; experimental method steps; pharmaceutical company, batch number, purity specification; dosage form, dose, route, method; drug status, such as anesthesia, sedation, analgesia; equipment model, sensitivity, accuracy; because the experimenter is skilled in operating skills Consistency is a reliable guarantee for repeatability and so on.

　　(3) Reliability

　　Reproduction animal models should strive to ensure that they reflect human diseases. In other words, you should strive to reflect specific diseases or specific functions, metabolism or structural changes in a specific and reliable manner. Diseases and signs confirmed by laboratory examinations or X-ray pictures, electrocardiograms, pathological slices, etc. Animals that tend to have specific lesions spontaneously should not be used, and they should not be used for diseases that are easily confused with replication diseases. For example, lead poisoning can be used as a model for rats, but its disadvantage is that it is prone to endemic animal pneumonia and progressive kidney disease. The latter is easily confused with nephropathy caused by lead poisoning and is not easy to determine. Pneumonia is caused by lead poisoning. It is easy to judge in gerbils because it is caused by their own disease. Usually, only lead poisoning can cause the corresponding kidney disease.

　　(4) Applicability and controllability

　　Animal models used in medical experimental research make future clinical applications possible, and it is easy to control the development of these diseases to facilitate the development of research, which must be considered and repeated. For example, estrogen can terminate early pregnancy in rats and mice, but not in humans. Therefore, it is not appropriate to use estrogen to replicate rat and mouse abortion models. When screening rats and mice for estrogen-active drugs, these drugs can usually terminate pregnancy. Once used by humans, they will not succeed. Therefore, if the compound is known to have estrogenic activity, it is meaningless to use the compound to observe the effects of abortion on rats or mice. In another example, it is not appropriate to use rats and mice as experimental peritonitis. Because they are highly resistant to Gram-negative bacteria and are unlikely to cause peritonitis. Some animals are particularly sensitive to certain virulence factors and are very lethal, so they are not applicable. For example, peritonitis caused by intraperitoneal injection of canine fecal filtrate quickly died (80% died within 24 hours), it was too late, experimental treatment and observation, and fecal dosage were not possible, and bacterial strains were not easy to control. Therefore, the experimental results cannot be accurately repeated.

　　(5) Ease of use and economy

　　When copying animal models, the principles of economic conditions should be followed, and the method of use should be implemented as easily as possible. Primates are most similar to humans and replicate similar disease models, but they are rare and expensive. Even macaques are rare, let alone orangutans and gibbons. Many small animals (mice, rats, hamsters, guinea pigs, etc.) can also replicate very similar human disease models. They can easily obtain a clear genetic background and control the microbes in the body. The model is: you can choose your own gender, weight, etc., are cheap and easy to obtain, and are easy to feed and manage, so you can use it as much as possible. Unless it is necessary or necessary to study special diseases (dysentery, polio, etc.), do not use primates. In addition to the feasibility and economic principles of animal selection, these principles should be paid attention to when observing model replication methods and indicators.