动物造模,动脉粥样硬化模型,药效评价 zi-bio 2024-05-20 559

　　(1) Reproduction method: 6-8 week old ApoE gene deficient mice (strain C57BL/6J), half male and half female, weighing 18-20g, fed with ω (Fat)=21% ω (Cholesterol)=0.15% of "Western type diet" feed (treated with 60CO sterilization and irradiation), feeding conditions are level 2, room temperature is maintained at 22-24 ℃, and relative humidity is 50%. Animal orbital blood collection and anticoagulant serum separation for blood lipid testing. After 20 weeks, the mice were euthanized, 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.