疾病动物模型,动脉粥样硬化 z-bio 2021-03-09 245

　　Animals are usually used, such as rabbits, pigs, rats, chickens, pigeons, monkeys, and dogs. Commonly used copy methods are:

　　1. High-cholesterol and high-fat feed method: At present, it is a more commonly used method, which has the characteristics of low mortality and long-term observation, but it is time-consuming. Generally, rabbits, pigeons, chickens, etc. can cause obvious hyperlipidemia after a few weeks of feeding, and early atherosclerotic lesions can form after a few months. Rats, mice and dogs are more difficult to form. You can add egg yolk, cholic acid and lard to your diet to promote your diet. Methionine, propylthiouracil, methionine, amphetamine, vitamin D, nicotine or sucrose can also be added to a high-fat diet to promote the formation of lesions.

　　Specific replication method: rabbit-induced model: body weight is about 2 kg, daily cholesterol is 0.3 g, 4 months later, aortic atherosclerotic plaque is visible to the naked eye. If the daily dose is increased to 0.5g, plaques will appear after 3 days. One month; if it is increased to 1 gram per day, it can be reduced to 2 months. Add 15% egg yolk powder, 0.5% cholesterol and 5% lard to the diet. After three weeks, after subtracting the cholesterol in the feed, the incidence of aortic plaque reaches 100%, and the serum cholesterol can be Increase to 2000 mg%. Rat-induced model: 1-4% cholesterol, 10% lard, 0.2% methylthiouracil, 86-89% basic diet, 7-10 days or 10% protein yellow powder, 5% lard , 0.5% bile salt, 85% basic diet, hypercholesterolemia can be formed after 7 days. Mouse-induced model: male mice were fed a high-fat diet of 1% cholesterol and 10% lard, and serum cholesterol increased to 343±15 mg after 7 days. If 0.3% cholic acid is added to the diet, continue feeding. For 7 consecutive days, serum cholesterol can reach 530±36 mg%. Chicken and pigeon-induced model: Enjoy chicken in a 4-8 week old lake, add 1-2% cholesterol or 15% egg yolk powder to the feed, then add 5-10% lard, 6-10 blood cholesterol liters Up to 1000 in a week? 4000 mg%, the incidence of thoracic aortic plaque reaches 100%. Pigeons can get 3 g/kg/day cholesterol and 0.1 g methylthiouracil every day, which can produce more animal plaques.

　　2. Immunological method: Injecting rat aortic homogenate into rabbits can increase blood cholesterol, β-lipoprotein and triglycerides. Rabbits were injected with horse serum at 10 ml/kg/dose four times every 17 days. The intimal injury rate was 88%, and the coronary arteries also had atherosclerotic lesions. -Cholesterol diet, the lesions are more obvious. Drinking a 1% cholesterol-containing beverage and intravenous injection of 250 mg/kg bovine serum albumin to rabbits may accelerate the formation of endometrial lesions caused by a high-cholesterol diet.

　　3. Catecholamine injection: Give the rabbit an intravenous drip of norepinephrine 1 mg/day for 30 minutes. One method is to inject for 15 minutes, rest for 5 minutes, and then inject for 15 minutes. Another method is to inject for 5 minutes, let it stand for 5 minutes each time, and then repeat 6 times. The above two methods last for two weeks and can cause aortic disease. This indicates that the elastic fibers in the middle layer of the blood vessel wall are stretched, split or destroyed, necrosis and calcification appear in the disease.

　　4. Homocysteine injection: dl-homocysteine thiolactone (dl-homocysteine thiolactone) subcutaneous injection dose is 20-25 mg/kg/day (concentration in 5% glucose solution is 1 mg/ml) -25 days. Homocysteine atherosclerosis can occur in adult and young rabbits. Coronary artery lumen narrows, arterial wall intima myocyte hyperplasia, fibrous tissue hyperplasia, elastic fiber breakage, thickening of catheter wall and piles of granular and fibrous hybrid materials appear in the matrix. When 20% cholesterol is added to the diet and homocysteine thiolactone is injected at the same time, all animals will have severe atherosclerotic lesions.

　　5. Surfactant injection: TritonWR1339 300 mg/kg was injected into the abdominal cavity of the rat. After 9 hours, the serum cholesterol increased 3-4. After 20 hours, the serum cholesterol of male rats was still 3-4 times higher than the normal level, but It is about 6 times higher than that of female rats, and the lipid-lifting effect reaches its highest point at about 24 hours and about 48 hours after administration. It will return to normal. Among them, the increase in triglycerides was the strongest, followed by phospholipids, free fatty acids and free cholesterol, which did not affect cholesterol lipids.

　　6. Intravenous injection of cholesterol fat emulsion: Dissolve 3 grams of cholesterol and lard under electromagnetic heating and stirring, add 803 grams of Tween and stir well, then slowly add 5 ml of propylene glycol and boiling water and stir well to emulsify to 100 ml. After suction filtration, confirm with a microscope that the emulsion particles are uniform and can be used in the range of 7-8μm or less. Intravenous injection of 5 ml/kg of plasma cholesterol and triglycerides into rabbit ears immediately increases. The total cholesterol is increased by 6 times than normal, and the free cholesterol is mainly free cholesterol, and the ratio of free cholesterol to total cholesterol is 90%. After that, the total plasma cholesterol gradually decreased, a low peak appeared at 6 hours, and then slightly increased. After 3-4 days, the ratio of free cholesterol to total cholesterol is close to the normal level (about 40%), until plasma cholesterol returns to normal after 7-14 days.

　　7. Method for immature rats: Due to the high fat content in milk and decreased thyroid function, the serum cholesterol of immature rats is usually 2-3 times that of adult rats. When using conventional feed instead of milk feed, serum cholesterol quickly dropped to the level of normal adult rats. The experiment selected 25-day-old lactating white rats (male and female), weighing 30-50 g, and observed the effect of the drug in lowering blood cholesterol without separation from the lactation of mother rats. Compare this effect with the control group. It is generally believed that this type of hypercholesterolemia is very sensitive to thyroxine and its derivatives, but not sensitive to certain cholesterol biosynthesis inhibitors.

　　8. Other methods: There are many factors that can induce hyperlipidemia and atherosclerosis. For example, cerebral ischemia in animals, electrical stimulation of the central nervous system, high stress conditions, exposure to large amounts of estrogen and carbon monoxide in birds, and balloon damage to endothelial cells in the arterial wall. Characteristics of various animal models of hyperlipidemia and atherosclerosis: Except for rats and hamsters, warm-blooded animals usually have atherosclerotic plaques that can form lesions as long as they use appropriate methods.

　　⑴ Rabbit is the earliest animal used to simulate hyperlipidemia and atherosclerosis, and it is still used in many cases. Highly absorbed exogenous cholesterol is as high as 75-95% in rats and only 40%. The ability to eliminate hyperlipidemia is very low. After intravenous injection of cholesterol, blood lipids can last for 3-4 days, but rats only have 12 hours, and dogs are somewhere in between. As long as the rabbits are fed a hypercholesterolemia diet, no other factors are needed. Obvious atherosclerosis can be formed within 3-4 months, similar to the pathological changes that occur in the human body, and it is convenient to take. Blood used for testing. However, it also has some disadvantages, such as the need to reach high levels of serum cholesterol to form plaques. At this time, the internal organs are prone to lipid deposition, the life of the animal is short, the resistance is low, and it is easy to die due to secondary infection. In addition, rabbits are herbivores, and the metabolism of esters is completely different from that of humans. Experiments have shown that the coronary artery lesions in rabbits are mainly in the small arteries of the heart, while in humans, they are mainly located in the large branches of the coronary arteries.

　　⑵White mice use white mice to establish hyperlipidemia and atherosclerosis models. It has the advantages of convenient feeding, strong resistance and similar human eating habits. The resulting pathological changes are similar to those in the early stages of humans, and it is not easy to form late lesions similar to those of humans, and it is also easy to form thrombus. The average serum cholesterol in normal rats was 92.67±1.87 mg%. Increasing cholesterol in the diet alone is not easy to cause an increase in serum cholesterol and atherosclerosis. Cholic acid must be added to the diet at the same time to increase the absorption of cholesterol, which may lead to hypercholesterolemia, such as adding antithyroid drugs. It can further increase serum cholesterol.

　　⑶ White mice The advantage of making experimental models with white mice is that it is easy to grow and store drugs, but because blood collection is inconvenient and difficult to observe dynamically, it is rarely used.

　　⑷Chicken is an omnivorous animal whose food type is similar to that of humans. Simply adding cholesterol to the daily diet can form atherosclerotic plaques. The lesions develop rapidly, sometimes accompanied by plaque calcification and ulcers.

　　⑸ The pigeon is similar to the chicken. Feeding is easy. Adding cholesterol to the diet can cause atherosclerotic plaque in the aorta, which can lead to myocardial infarction. Due to different breeds of pigeons, the nature of atherosclerotic plaques may be very different. This may be due to differences in lipase activity between individuals.

　　Monkey Regardless of the normal blood lipids, the nature and location of atherosclerosis, the clinical symptoms and the therapeutic effects of various drugs, the situation of monkeys is very similar to that of humans. However, further studies have shown that different species have different sensitivity to atherosclerosis. It is generally believed that rhesus monkeys are ideal. After 1-3 months of a high-fat diet, serum cholesterol levels can reach 300-600 mg%. At the same time, atherosclerosis is found, which may cause myocardial infarction. Atherosclerotic lesions are found not only in the aorta, but also in the coronary, brain, kidney and femoral arteries.

　　Pig pig may be an ideal animal model for studying atherosclerosis. This is because certain breeds of old pigs will cause serum atherosclerotic lesions in arteries, coronary arteries and brain after feeding leftovers. It is very similar to human lesions. Eating only high cholesterol and high fat diets can cause experimental atherosclerosis in a relatively short period of time (9-18 months). In addition, through probe puncture and high cholesterol and high fat diet can quickly produce progressive aortic and coronary atherosclerosis. Other benefits of the pig model include human-like anatomy and physiology, similar arterial structure, available several confirmed variants, multiple births, omnivorous, etc., and their sizes are all different enough for surgical and clinical evaluation. Pigs are also particularly suitable for studying the relationship between stressors and atherosclerosis. The disadvantage of the pig model is that it needs to spend a certain amount of feeding costs, and artificially causing atherosclerosis requires the basis of lipid metabolism or arterial damage to change.