动物模型 z-bo 2020-08-14 384

　　(1) The influence of modeling factors on the reproduction of animal models

Choosing good modeling factors is the first step in replicating an animal model. The purpose of the research should be clarified, the occurrence, clinical symptoms and pathogenesis of the corresponding human diseases should be clear, and the clinical symptoms and pathogenesis of the animal caused by the pathogenic factors should be familiar with the pathogenic factors. The dosage, the animal’s genetic background, gender, age, etc. have certain effects on the replication of the model. Choose appropriate pathogenic factors and try to avoid choosing experimental animals with small similarities to human organs as animal models to increase the similarity between the replicated animal models and human diseases. For example, the pathological manifestations of atherosclerosis in rabbits are mainly fibrous tissue and smooth muscle hyperplasia. These phenomena are somewhat different from human conditions. This requires researchers to fully understand all information such as pathogenic factors, animals and methods, and analyze energy Whether to achieve the expected result.

　　 (2) The influence of animal factors on the reproduction of animal models

　　 There are many kinds of animals that replicate animal models, such as experimental animals, economic animals and wild animals. Wild animals belong to a natural ecological type, with complex microbial infections, unclear genetic background, difficult sources, and difficult to raise, so they are inconvenient to use; economic animals are convenient to raise and source, but the microorganisms are not strictly controlled, genetic background is not clear, and inconvenient to use . The most widely used is standardized laboratory animals. Improper selection of animals will affect model replication and affect experimental results.

  1. The influence of animal species There are certain commonalities in the life phenomena of different species of mammals, but there are also many differences. Improper selection of animal species will affect the experimental results. For example, gossypol acetate can affect male reproductive function. Mice are not sensitive, while rats and guinea pigs are very sensitive. Pig skin and blood vessels are similar to humans. It is the first choice for burns, scalds, and vascular surgery experiments. The experimental results are close to clinical reality, and rodents cannot be selected for this type of model; mice are suitable for geriatric research due to their short lifespan and short passage time, because large animals should not be used to replicate models for this type of research.

  2. Effects of animal strains Animals of the same species but different strains have different responses to pathogenic factors. The corresponding strains of animals should be selected according to the experimental purpose to replicate the animal model. For example, 100% of DBA/2 mice at 35 days can develop auditory seizures, while C57BL mice do not have this phenomenon at all.

The sublines of 　　 inbred lines are different from the original inbred lines and cannot be regarded as the same kind. There are also gene mutations and genetic drifts caused by long-term preservation and improper breeding of inbred lines. The first hybrid (F1) is the first hybrid of two inbred lines. It has good homogeneity between individuals and strong tolerance to experiments. It makes up for the shortcomings of inbred lines, but does not necessarily maintain all the characteristics of the original inbred lines. The genetic characteristics and response performance of outbreed strains remain relatively stable, with strong vitality, high reproduction rate, strong disease resistance, and mass production, but the repeatability and consistency between individuals are not as good as inbred strains and F1 animals. . Only by clarifying the purpose of the experiment and understanding the characteristics and characteristics of the animals can the most effective release of the influence of strains on the replication model.

　　3. The effect of animal age and weight When selecting an animal replication model, attention should be paid to the animal’s age and weight. Animal lifespans vary greatly. Under the condition of various factors being fixed, the animal's weight and age should be linearly related within a certain range, especially for standard laboratory animals. If the weight does not match the age, it should be regarded as an unqualified laboratory animal.

Animal anatomical and physiological characteristics and responsiveness change significantly with age. Generally, young animals are more sensitive than adult animals, and elderly animals are less sensitive. If the model time is longer, you should choose young animals, prepare diabetes models and replicate some animal models of senile diseases. Use old animals. According to the purpose of the experiment, the corresponding animal replication model should be selected to reduce the influence of age and weight on the accuracy of the experimental results.

　　4. Experiments on the influence of animal gender factors have shown that animals of the same species and strains of different sexes do not respond to certain factors inconsistently. There are also large differences in the responsiveness of female animals to certain factors at different stages of the sexual cycle and during pregnancy and lactation. . When choosing sex, male animals or half males are generally selected. For example, ergonovine has analgesic effect on male rats of 5 to 6 weeks, but not female rats. For the reproduction of some special models, females must be selected. In short, the sex of the animal should be selected according to the purpose of the experiment.

　　 5. The effects of animal physiological status and health factors Animals have very different responses to pathogenic factors when their physiological conditions are different. For example, female animals have inconsistent responses to external pathogenic factors when they are pregnant or breastfeeding compared with other periods. Animal health status is different, and the response to external factors is also inconsistent. For example, when replicating liver failure animal models, rabbits with severe coccidiosis cannot be selected, otherwise the test results are inaccurate and the experimental results will be affected. There are many factors that affect animal health, such as viruses, bacteria, and parasites.

　　 (3) The influence of experimental technical factors on the replication of animal models

  1. The reaction of animals to the outside world during the experiment season is also affected by different seasons of spring, summer, autumn and winter. For example, a certain dose of barbital sodium was injected into experimental rats. It was observed that the time to fall asleep was the shortest in spring and the longest in autumn. Another example is the increase in radiation sensitivity of rabbits in spring and summer, and decrease in autumn and winter. In different experimental seasons, the responsiveness of animals has certain changes in certain aspects. This effect should be paid attention to when conducting cross-season animal model experiments.

  2. The different time of day and night affects the body temperature, blood sugar, basal metabolic rate, secretion of endocrine hormones, etc. of experimental animals, which changes rhythmically with the difference of day and night. For example, to inject 0.2ml of 40% carbon tetrachloride solution into mice, observe the mitotic dynamics of hepatocytes at different times on the same day, and the results confirm that the circadian changes of hepatocyte mitosis in mice are very obvious. Therefore, when copying animal models for experimental research, one should pay attention to the influence of the time sequence of certain treatments in the experiment on the results. The time for collecting samples should be fixed.

　　3. The effect of depth of anesthesia When replicating an animal model, it is often necessary to anesthetize the animal before performing various operations and implementing certain modeling methods. Different types of anesthetics and doses of anesthesia have different pharmacological effects and adverse reactions. For example, if the anesthesia is too deep, the animal is in a deeply inhibited state, or even a state of dying, various animal reactions are inhibited, and the reliability of the results is affected; too shallow anesthesia, Performing an operation on an animal or implementing a certain modeling method will cause intense pain and irritation, causing changes in the animal's whole body, especially the respiratory, circulatory, and digestive systems, and will also affect the accuracy of modeling. Therefore, it is required to use the same anesthetic in the same experiment, and the depth of anesthesia must be kept constant throughout the experiment (including model building in the control group). In addition, anesthetics should be selected according to the purpose of the experiment and the species and strains of the animals to eliminate the effects of anesthetics and the depth of anesthesia.

　　4. The influence of surgical techniques When making experimental surgical models, the best surgical route must be selected first, so as to avoid excessive and complicated operations from affecting the animal body. Proficiency in surgical techniques is also an influencing factor. Proficiency in surgical techniques can reduce irritation, trauma and bleeding to animals, and will increase the success rate of modeling.

　　 5. Experimental dosing effects Dosing is a routine task in the modeling process, but it is also a factor that affects the modeling, such as the route of administration, dosage, and proficiency. For example, intravenous administration in mice, if the tail vein of the mouse is not found, or unskilled injection into the subcutaneous can cause tissue damage; in mice, if the gastrointestinal tract is administered, the drug will be injected into the respiratory tract if unskilled, or the tissue will be seriously damaged. Causes animal disease and death, and has a serious impact on modeling work. The effects of different administration routes in animals are also inconsistent. If some hormones are destroyed in the liver, oral medication will affect their effects. In the process of model building, if the dosage of human medicine is converted to animals (calculated by weight), the dosage of animal medicine is too small, which is often ineffective. If the dosage of animal medicine is converted to human, the dosage of medicine is too large, causing adverse reactions. The conversion of doses between humans and animals or between different animals cannot simply rely on body weight (such as giving the same dose of drug per kilogram of body weight), but should rely on body surface area, that is, giving the same dose of drug to the same body surface area between different species. It is currently recognized and the most commonly used method of dose conversion between different species.

　　The calculation of the dose between animals can refer to the following formula:

　　 A dose (mg/kg) × A Km factor = B dose (mg/kg) × B Km factor

　　 Among them, A and B represent two different animals, and different animals have different Km factors. The body weight, body surface area and Km factor of human and common animals are shown in Table 1-1.

　　6. The influence of the control group on model building When copying an animal model, it is often because of the neglect or wrong application of the control problem that the animal model fails or leads to wrong conclusions. There are many ways to set up control, such as blank control, experimental control, effective (or standard) control, paired control, historical control, normal value control, etc. The control group should be set according to different requirements.

　　 (4) The influence of environmental and nutritional factors on replicating animal models

　　 Nutritional factors have a significant impact on replicating animal models, especially long-term experiments, which should be paid attention to. If the national standard feed is adopted, the problem will be solved. During the modeling process, attention should be paid to adequate water supply and drinking water that meets sanitary standards.

　　 Animals can adapt to temperature changes within a certain range, but it is difficult to adapt to temperature changes too fast. Too high humidity can easily cause microbial reproduction and animal diseases; too low humidity and flying dust can also cause animal diseases; humidity beyond a certain range will put the body in a state of stress, causing the animal body to react abnormally to many modeling factors. Affect modeling work. If the air velocity is too high, the temperature around the animal will be too low. If the air velocity is too low, the concentration of harmful gases such as ammonia and hydrogen sulfide will be too high. This requires proper air velocity to maintain fresh air. Illumination is closely related to animal sex cycles. Too much or too little intensity is harmful to animals; noise makes animals nervous and irritated, causing abnormal behavior and physiological reactions of animals, and affecting the work of replicating models. The living density of animals is a social factor of animals. Too dense or too sparse will affect the relationship between animals and animals. Living too densely will cause poor sanitation, excessive excrement, increased ammonia concentration, and excessive microbial reproduction.

　　 In short, the success or failure of replicating animal models is closely related to environmental factors. Housing, feed, nutrition, light, noise, ammonia concentration, temperature, humidity, air velocity, etc. cannot be ignored. The important measures to solve and overcome these factors are: use national standard feed, purchase standard-qualified laboratory animals, replicate animal models in standard animal laboratory facilities, raise and laboratory technicians should obtain qualification certificates, and use standard reagents, drugs, etc. . In addition, we should pay close attention to the management of standard facilities. Failure of the barrier system will also affect the replication of animal models of human diseases.