动物造模,动脉粥样硬化动物模型,药效评价 zi-bio 2024-10-30 1494

　　Dietary induction method

　　The response of different animals to cholesterol is completely different, with rabbits being the most sensitive to cholesterol, while rodents (such as mice and rats) have almost no response to cholesterol. In 1908, Ignatowski, a Russian pathophysiologist, fed rabbits with a diet rich in animal protein to induce atherosclerosis, opening a new era of experimental research on atherosclerosis. Therefore, the rabbit is an ideal animal model for the study of atherosclerosis induced by diet.

　　[Modelling mechanism] The disorder of lipid metabolism in animal body and the rise of blood lipids are likely to cause damage to the vascular endothelium, leading to dysfunction of the vascular endothelium, increased permeability, and eventually leading to lipid infiltration in the vascular wall and atherosclerosis. Therefore, by feeding the experimental animals with high-fat and high cholesterol diet, hyperlipidemia appears, and then the aorta and coronary arteries are gradually induced to form atherosclerotic plaque. Adding a small amount of bile salts to a high fat and cholesterol diet can increase cholesterol absorption; Adding thyroid suppressants such as methylthiouracil and propylthiouracil can further accelerate the formation of arterial lesions.

　　Modeling method

　　Rabbits: male Japanese big ear white rabbits or New Zealand rabbits about 4 months old were selected and given a diet containing 0.3% cholesterol (the recommended cholesterol level in the diet is less than 0.6%), which can rapidly increase the plasma cholesterol of rabbits. After 6 weeks, the aortic arch of rabbits can appear obvious atherosclerotic plaques. With the prolongation of feeding time, atherosclerotic plaques could be induced in the thoracic aorta, abdominal aorta and coronary artery of rabbits.

　　Small pigs: Select small pigs aged 3-6 months. The atherogenic diet formula: cholesterol 1.5%~2%, butter 10%, peanut oil 6%. Bile salt 0.5%~1%, base material 82%~83%. Small pigs are usually fed at a weight of 3%.

　　Rats: High fat and cholesterol diet containing cholic acid and thiouracil induces hyperlipidemia and atherosclerosis in rats. In addition, rats fed with a high cholesterol diet and a large amount of vitamin D2 could increase the plasma cholesterol level and cause atherosclerotic plaques in the aorta and coronary arteries.

　　Mice: C57BL/6 mice of 6-8 weeks were fed with a diet containing 1.25% cholesterol, 0.5% bile acid and 15% fat for 10 weeks, which can induce early atherosclerosis.

　　Other animals: chickens of 4-8 weeks old were given a diet of high cholesterol (1% -2%) and high fat (5% -10% lard). After 6-10 weeks, the incidence of aortic atherosclerotic plaque reached 100%. Pigeons fed with 3 g/kg cholesterol and 0.1 g methylthiouracil every day can produce obvious atherosclerotic plaque.

　　Model Features

　　Rabbits: When the cholesterol content in the high-fat diet reaches 0.2%~2.0%, the cholesterol concentration in the plasma of rabbits will rise rapidly, and hypercholesterolemia will occur, starting the occurrence and development of atherosclerosis. As the cholesterol content in the diet increases and the feeding time prolongs, the plaque on the arterial wall of the rabbit gradually increases. However, the higher the cholesterol content in the diet