动物造模,神经系统疾病动物模型 z-bio 2022-03-23 404

　　The progression of human diseases is very complicated. It is used as an experimental object for humans to explore the mechanism of disease. The process of facilitating drug development is slow. The accumulated clinical experience is not only limited in time and space, but many experiments are ethically based on methods. By indirectly studying animal models, consciously changing factors that are impossible or difficult to exclude under natural conditions, and observing the experimental results of the model more accurately and comparing them with human diseases, you can conduct research. It makes it more convenient, helps us more effectively understand the laws of human disease development and development, and helps us to study prevention and treatment measures. Animal models of human diseases (animal models of human diseases) refer to animals that mimic human disease symptoms in various medical scientific researches. Animal models are mainly used for experimental physiology, experimental pathology and experimental treatment research. The replication of animal models of neurological diseases uses artificial methods to cause specific diseases, nerve tissues, organs or animal pathogenic factors (physical, chemical, biological), thereby causing certain damage to the entire animal body. Similarity By using the function, metabolism, morphology and structural changes of human nervous system diseases and various diseases, this method can be used to study the occurrence and onset of human diseases, as well as to study the prevention and treatment of human nervous system diseases. The theoretical basis. According to the anatomical structure of the nervous system, animal models of nervous system diseases can be divided into animal models of peripheral nervous system diseases and animal models of central nervous system diseases. Virulence factors can be divided into traumatic animal models, animal models of metabolic diseases, animal models of dysplasia, animal models of hereditary metabolic diseases, animal models of psychosis, and other animal models. In addition to the general classification of the surrounding environment and the central nervous system according to the environment and the location of the disease, it can also be classified into different models according to the location of the disease.

　　1. Animal model of peripheral nerve disease

　　Peripheral nerve injury only accounts for 1.5% to 4.0% of all traumas, but it mainly leads to severe limb dysfunction, such as movement disorders, sensory disorders and nutritional disorders. The failure rate is high. The location and degree of peripheral nerve injury are different, and the clinical symptoms that occur are also different. Due to the special anatomical structure and function of the peripheral nerve, the selection of appropriate experimental animals and the method of establishing the model have a great impact on the research of peripheral nerve injury and repair. According to the type of nerve injury, it is mainly divided into compression injury, traction injury and amputation injury. Fracture injury refers to the passage of peripheral nerves through a specific bone fiber tube. In some cases, the fiber ends are compressed and damaged for a long time, causing inflammation, abnormal nerve function, local blood supply, and continuous destruction of axons in the damaged part of the nerve. At present, peripheral nerve compression injury is mainly acute and chronic nerve compression injury. The method used to establish a model is to use external forces such as clamps, cable ties, etc. to destroy the injured nerve and cause certain injuries. It simulates the clinical manifestations of the human body, thereby simulating the process of personal injury.

　　二. Spinal cord injury animal model Spinal cord injury (SCI) has a high disability rate and fatality rate, which not only brings suffering to patients, but also brings a heavy burden to society and families. As early as 1911, Allen used the weight loss (WD) method to create an animal model of spinal cord injury for the first time, marking the beginning of experimental spinal cord injury research. Since then, new animal models of spinal cord injury have continued to appear, including animal models of mechanical, electrical, laser, ischemia, and chemical injury. At present, according to the type of mechanical injury, it can be divided into animal models of shock, compression, extension, amputation, concussion, clamp, ischemia and other injuries. At present, the most commonly used research tool is the rat, and most of the model injury segments are from T5 to T12. Currently, there are many animal models to choose from to study spinal cord injury, but the progress is relatively slow. The reason is that the pathophysiological mechanism after spinal cord injury is very complicated, people have not yet fully understood it, and it is comprehensive. Especially in recent years, related studies on the role of the microenvironment after spinal cord injury and various neurotrophic factors after spinal cord injury have put forward higher requirements for animal models of spinal cord injury. Therefore, different animal models and clinical spinal cord injuries are still very different. Each model can only represent certain aspects of spinal cord injury, and each model has its advantages and disadvantages. However, due to the efforts of scientific researchers, people have improved the way of modeling spinal cord injury, reduced the differences between models, and more accurately determined the injury site and injury. In the future, animal models of spinal cord injury that are closer to the clinic, more reliable, standardized, highly controlled and reproducible will be created.

　　3. The memory of animal models of memory impairment is a very complicated process. Mainly include: memory acquisition, memory consolidation, memory regeneration. Therefore, animal models of memory impairment are mainly created in these three stages. The memory acquisition disorder model is mainly created by specific drugs (for example, Eastpol base, pentobarbital sodium, reserpine, and sodium nitrite). The memory integration disorder model cannot maintain the animal's memory, mainly using electric shock, hypoxia, inhibition of protein synthesis, carbon monoxide poisoning, etc. Models of memory and aplastic disorders are usually made by injecting alcohol. In addition, there are mixed memory impairment models, which mainly include hypertension, dementia, trace elements, noise, etc., to cause mixed memory impairment in animals.

　　4. Animal models of extrapyramidal diseases The animal models of extrapyramidal diseases are mainly animal models of Parkinson's disease. Its clinical features are resting tremor, muscle stiffness and slow movement. The etiology is not clear. It is generally believed that it is mainly related to aging, genetics and environmental factors. At present, the most obvious pathological changes are the degeneration and necrosis of dopamine (DA) neurons in the substantia nigra compact area, as well as the appearance of Lewy bodies, which are characterized by a decrease in DA synthesis, which leads to changes in neurobiochemistry in the body. .. Such models mainly include neurotoxin models, gene knockout models, transgenic models, immune or mechanical injury models, and mainly cause Parkinson's disease-related symptoms in animals.

　　5. Animal model of paroxysmal disease Epilepsy is a chronic recurrent transient brain dysfunction syndrome, which is characterized by recurrent epilepsy caused by abnormal discharge of brain neurons. Animal models are mainly based on common tonic-clonic seizures (grand seizures), simple partial epilepsy, complex partial epilepsy, absence seizures (mild seizures), status epilepticus and other clinical manifestations, and can be divided into models. It is usually divided into electric shock model, chemical induction model, hereditary seizure model and chronic experimental model. Among them, the electric shock model is the most common. The chemical induction model is mainly used to explain the mechanism of the compound in suppressing epileptic seizures. Commonly used chemical shock absorbers are camphor, strychnine, pentylenetetrazol, dicitrulline, alanine propylene glycol, microtoxin, isoniazid, 3-mercaptopropionic acid and aminophylline.

　　6. Animal models of demyelinating diseases It is difficult to remyelin the central nervous system after demyelination. The specific mechanism is unclear. Currently, central nervous system demyelinating animal models mainly include experimental autoimmune encephalomyelitis models, toxin models, virus models, transgenic and gene knockout models. The experimental autoimmune encephalomyelitis animal model is prepared by immunizing animals with myelin components that cause central nervous system inflammation, such as myelin glycoprotein, myelin protein lipoprotein, and myelin-related glycoprotein. The establishment of a toxin-induced demyelination model is mainly through eating or injecting toxins to act on myelin to trigger the demyelination reaction. Commonly used chemicals are copper ketone, ethidium bromide and lysolecithin.

　　7. Motor neuron disease animal model Motor neuron disease is a chronic progressive degenerative disease that selectively invades the anterior horn cells of the spinal cord, brainstem motor neurons, cortical pyramidal cells and pyramidal tracts. The clinical manifestations are various combinations of weakness, muscle atrophy and pyramidal tract signs, usually without sensory or sphincter disease. This mainly includes animal models of motor neuron diseases caused by drug toxicity, spontaneous animal models, transgenic animal models, immune motor neuron disease models, and in vitro cell or tissue culture models. Corticospinal tract involvement is an important feature of motor neuron disease. However, most animal models currently cannot achieve selective corticospinal tract involvement. This is a major obstacle to the development of animal models of motor neuron disease, because only primates in the animal kingdom have corticospinal tract structure and functional characteristics similar to humans.

　　8. Animal models of dementia Dementia refers to chronic acquired progressive intelligence syndrome. Clinically, its main characteristic is a slow decline in intelligence and varying degrees of personality changes. It is a group of clinical syndromes, not independent diseases. Therefore, there are many experimental animal models, and as long as the experimental animal shows symptoms of dementia, it can be classified as a dementia model. The research mainly includes Alzheimer's disease animal models and vascular dementia models. There are many types of animal models of Alzheimer's disease. The main research idea is to simulate the behavioral changes and pathological products of animal Alzheimer's disease. It is close to objective facts and leads to changes in animal Alzheimer's disease, mainly through physical, chemical or genetic changes. Vascular dementia models mainly use surgical or chemical methods to block the corresponding blood vessels in the animal's brain, or cause ischemia and hypoxia, leading to pathological changes in the brain.

　　9. Depression animal model

　　There are many ways to simulate depression. Most models can simulate the behavioral characteristics of depression patients from the perspective of clinical symptoms, and simulate the neurotransmitters of depression patients from the perspective of molecular biology. species. Mainly chronic and unpredictable stimuli (tilting, fasting without water, tail clip, ice bath, heat stress, wet garbage, day and night reversal, horizontal vibration, etc.), forced swimming experiments in mice, mice Tail suspension experiment, reserpine experiment, rat olfactory bulb resection model, focal cerebral ischemia model, rat acquired frailty experiment, transgenic animal model, etc. In recent years, molecular biology has been widely used in psychiatry. In the process of creating the depression model, some new advanced technologies and methods were also introduced. Scholars used plasmid transfection to express glucocorticoid receptor mRNA antisense RNA in rats, thereby creating a transgenic animal similar to depression. This model is believed to be replicated through the experiment of suppressing depression with dexamethasone.

　　10, nervous system tumor animal model

　　The establishment of an animal model that highly mimics human brain tumors is an indispensable and important research tool for neurosurgery. Early brain tumor animal models mainly used laboratory animal chemistry or viral induction to produce brain tumor transplantation model tumors. Its limitations are mainly manifested in the instability caused by animal models and the difficulty of storing laboratory materials. Current methods mainly include brain tumor transplantation models and transgenic animal models. In particular, transgenic brain tumor models and gene knockout brain tumor models are established based on the combination of in vitro and in vivo, which act on the molecular and cellular levels and have an effect on the whole animal level. Therefore, it is possible to study the genetic etiology of brain tumors, the immunological relationship between brain tumor cells and the human body, and the development and evolution of brain tumors from a more complete system.

　　11. Animal model of head injury

　　Traumatic brain injury (traumatic brain injury, TBI) is an important part of trauma, which usually leads to loss of consciousness, amnesia and neurological dysfunction. The experimental conditions are relatively well controlled, and there are many animal models, because such models are mainly caused by external forces. Common models include free fall injury model, hydraulic impact injury model, controllable cortical impact injury model, craniocerebral firearm injury model, cranial partial air impact injury model, direct injury model, negative pressure injury model, acceleration and deceleration. Rotation damage. Models, ischemic head trauma models, brain cryosurgery models, brain injury and combined injury models, etc. The occurrence of brain injury in real life is highly unpredictable and complex. Scientific research prepares more types of craniocerebral trauma models to adapt to different types of brain injury research, and has better controllability, repeatability, stability, etc.

　　12. Animal model of nervous system poisoning Neurotoxin is a toxic substance targeting the nervous system. Its main feature is that it interferes with the function of the nervous system, causes corresponding symptoms and signs of poisoning, and can be fatal in severe cases. Symptoms of neurotoxicity occur when the human body inhales or comes into contact with related neurotoxins. Also make animal models based on the corresponding toxins. Common toxins include carbon monoxide, aluminum, ethanol, organophosphorus and heroin. The above only outlines the animal models of common neurological diseases, but in some experimental procedures, these models far exceed these models. For example, animals can be used as models to simulate the complications of neurological diseases. The clinical manifestations of the nervous system can also be classified as animal models of nervous system diseases. With the deepening of research, more and more models will appear, and we will improve them on the basis of the original model to create new models. A good disease model should have the following characteristics: (1) It must have high reproducibility to reproduce the human disease under study, and have animal disease manifestations similar to human diseases. ②The animal background information must be complete, and the life cycle must meet the needs of the experiment. ③High replication rate; ④High specificity, that is, one method can only replicate one model. No animal model can replicate all the symptoms of human disease. After all, animals are not humans, and model experiments are only indirect studies. Diseases similar to human diseases can only occur partially or partially. Therefore, the correctness of the model experiment conclusions is relative and must be verified by the human body. If a phenomenon different from human diseases is discovered during the replication process, the nature and extent of the difference must be analyzed to find the similarities and differences in order to make a correct assessment.