动物模型 z-bo 2022-02-04 391

　　In the design of biomedical scientific research, the question of how to build animal models is usually considered, because there are currently no or should not be conducted on patients to clarify the mechanism and efficacy of many experiments. Will be done. Usually, this depends on the reproduction of the animal model, but it requires careful design. The following principles should be followed when designing:

　　One of

　　. Similar to human disease models of replicated animals. The goal is to find relevant methods that can be promoted (extrapolated) to patients. Extrapolation is risky, because neither animals nor humans are living things. 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 that the replicated model should be as close as possible to the situation of human disease. Of course, it is best to find naturally occurring animal diseases that are the same as human diseases. For example, the rat essential hypertension discovered by the Japanese is an ideal model for studying human essential hypertension, while the spontaneous coronary atherosclerosis of old sows is related to human coronary heart disease. It is an ideal mode of learning. Dog's spontaneous rheumatoid arthritis is very similar to human juvenile rheumatoid arthritis, and it is also an ideal model. After all, spontaneous models of animals that are identical to humans are rare and often need to be replicated manually. In order to resemble human diseases as much as possible, we must first pay attention to the choice of animals. For example, chicken plasma triglyceride, cholesterol and free fatty acid levels are very similar to humans, and the lipid composition of low-density lipoprotein and very low-density lipoprotein is also similar to humans, so the most suitable model. Second, the actual methods need to be continuously improved to make the model as humane as possible. For example, ligating the appendix blood vessels in rabbits can cause appendix necrosis and perforation, leading to peritonitis, which is different from perforation and peritonitis of acute obstructive appendicitis in humans. If you ligate the root of the appendix to the rabbit and maintain the original blood supply, this will cause the appendix. Perforation and peritonitis are ideal methods because they are similar to human conditions. If the animal type is different from the clinical situation, the clinic will not be able to provide effective treatment, and vice versa. For example, endotoxin shock (shock caused by intravenous injection of bacteria and their toxins into animals) is not exactly the same as clinical septic shock (septic shock), so it is effective for endotoxin shock in animals. .. This treatment has not been adopted by clinicians for a long time. Now, some people are turning to inject bacteria into the gallbladder of animals where the gallbladder ligates arteries and bile ducts to reconstruct a model of human septic shock. We believe that animals with both infectious diseases and endotoxin poisoning are similar to clinical septic shock. A series of checks are required to determine whether the copied model resembles a human. For example, someone can check and quantify the animal's pressure, pulse rate, venous pressure, respiratory rate, arterial blood pH, arterial blood oxygen and carbon dioxide partial pressure, venous blood lactate, blood volume, and other indicators. We found a shock model caused by static blood collection methods. Because it is very similar to clinical hemorrhagic shock, we believe that the model replicated by these methods is an ideal model. Similarly, when rhubarb is given to mice based on herbal theory, it looks like a human-like "spleen deficiency syndrome." If it is cured with Sijunzi Decoction according to the traditional Chinese herbal medicine theory, it is reasonable to regard it as an animal with human "spleen deficiency syndrome". model.

　　2. Reproducibility

　　The ideal animal model must be reproducible or standardized. For example, quantitative bleeding can lead to 100% hemorrhagic shock and 100% mortality, meeting repeatability and standardization requirements. Another example is the use of dogs as a model of myocardial infarction. It is ideal for thoracotomy in laboratory animals because the coronary circulation is similar to humans. However, the consequences of ligating a dog's coronary artery are very different. The results of ligating the same artery in the same part of the dog are very inconsistent, unpredictable and impossible to standardize. In contrast, the results of coronary artery ligation in rats, hamsters, and guinea pigs are relatively stable, consistent and predictable, so they can be standardized. Animal model replication, strain, age, gender, weight, health, feeding control, experimental and environmental conditions, seasons, circadian rhythm, pressure, room temperature, humidity, atmospheric pressure and disinfection are all used to improve the repeatability of animal model replication. Bacteria must be based on; experimental method steps; pharmaceutical company, batch number, purity specification, dosage form, dosage, route, method; anesthetic drugs, sedatives, analgesics, equipment models, sensitivity, precision; experimenter's technical ability. Consistency guarantees repeatability, so it stays consistent.

　　three. By Feasibility

　　Replicated animal models should strive to accurately reflect human diseases, that is, the specificity and accuracy of specific diseases or specific functions, metabolic or structural changes. The main symptoms and signs of the disease can be confirmed through laboratory examinations or X-ray pictures, electrocardiograms, pathological slices, etc. Animals that tend to spontaneously have certain corresponding lesions should not be used, nor should they be used for diseases that are easily confused with replication disorders. For example, rats can be used as a model of lead poisoning, but have the disadvantage of being prone to animal pneumonia and progressive kidney disease. The latter is often confused with kidney disease caused by lead poisoning, and it is not easy to determine whether the kidney disease is caused by lead poisoning or lead. Caused by my illness. In Mongolian gerbils, only lead poisoning usually causes the corresponding kidney disease, so it is easy to identify.

　　4. Applicability and controllability

　　Animal models of experimental medical research should be replicated to facilitate research, while taking into account the ease of future clinical applications and disease progression control. For example, estrogen can terminate early pregnancy in rats and mice, but not in humans. Therefore, it is inappropriate to use estrogen to replicate early pregnancy termination models in rats and mice. This is because when screening drugs with estrogenic activity in rats and mice, it is often found that these drugs can terminate pregnancy. This is an effective contraceptive, but once it is used by humans, it 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. Another example is that experimental peritonitis is not suitable for use in rats and mice because it has a high resistance to Gram-negative bacteria and is unlikely to cause peritonitis. Some animals are particularly sensitive to certain pathogens and easily die when not in use. For example, intraperitoneal injection of fecal filtrate in dogs caused rapid death from peritonitis (80% died within 24 hours), it was too late to observe experimental treatment, and stool dose and strain were well controlled. Since the results of the experiment have not been completed, it cannot be repeated accurately.

　　5. Ease of use and economy

　　When copying animal models, the methods used should be easy to implement and economical. Primates are most similar to humans, and replicate disease models are similar, but they are rare and expensive. There are no orangutans, gibbons, and monkeys. Fortunately, many small animals, such as rats, mice, hamsters and guinea pigs, can replicate very similar human disease models. They are easy to have a clear genetic background and can control the microorganisms in the body. The model is very stable. You can freely choose age, gender, weight, etc., and get the price easily. Yes, it is easy to provide and manage, so you can as much use it.