动物造模,药效评价,动脉粥样硬化 z-bio 2024-08-21 434

　　(1) Method of replication: ApoE gene deficient mice (C57BL/6J strain) aged 6-8 weeks, half male and half female, weighing 18-20g, were fed with a "Western type diet" feed containing 21% fat and 0.15% cholesterol (sterilized and irradiated with 60CO). The feeding conditions were level 2, with room temperature maintained at 22-24 ℃ and relative humidity of 50%. Animal eye socket blood collection, anticoagulant separation serum for blood lipid testing. The mice were euthanized at 20 weeks, and the heart and aorta were removed under sterile conditions and fixed with 10% formaldehyde. After 20 weeks of feeding, obvious atherosclerotic plaques were formed in the root of the mouse aorta, the intima was significantly thickened, the macrophages under the endothelium were clustered, and more foam cells and fiber caps were seen; After 13 weeks of continuous feeding, the lesion was further aggravated. He staining showed that the aortic root had obvious atherosclerotic plaque formation, obvious foam cells and lipid cores, thin fiber caps, local aggregation of macrophages, serious destruction of vascular membrane structure, lipid erosion, atrophy and calcification, showing the characteristics of vulnerable plaque. This model can also be fed with a high-fat diet containing 2% cholesterol for 16 weeks. After 16 weeks, the serum lipid level rises, and typical atherosclerotic plaques containing a large number of foam cells are formed in aortic sinus valve membranes, coronary arteries and other parts.

　　(2) Model characteristics ApoE gene deficient mice form obvious atherosclerotic plaques at the root of aorta, coronary artery and other parts after feeding a high-fat diet. The model animal ApoE gene deficient mice have clear genetic background, strong fecundity, lipid metabolism and plaques similar to human beings, and the animal is small, with less dosage, easy to feed and operate. It is an experimental atherosclerotic whole animal model suitable for screening anti As drugs.

　　(3) Comparative medicine ApoE gene deficient mice can spontaneously form hyperlipidemia and atherosclerosis. After modeling, the total cholesterol level in blood is 3~5g/L, which is close to the cholesterol level of human hyperlipidemia. However, the total cholesterol level of commonly used animals fed with high fat and cholesterol is as high as 7~10g/L. The development of atherosclerosis in model mice includes various stages, from lipid stripes to mature plaque covered with fiber caps. Similar to human As plaque, it is an ideal animal model for studying As plaque at present.