【Animal Modeling】-Genetic Engineering Atherosclerosis Model

  (1) Replication method 6-8 weeks old ApoE gene-deficient mice (C57BL/6J strain), half male, weighing 18-20 g, ω (fat) = 21%, ω (cholesterol) = 0.15% Western-style diet "feed (60CO sterile irradiation treatment)", the feeding condition is level 2, the room temperature is 22-24°C, and the relative humidity is 50%. Collect animal orbital blood, and use anticoagulant-separated serum for blood lipid testing. The mice were sacrificed at the 20th week, and the heart and aorta were taken out under aseptic conditions and fixed with 10% formaldehyde. After 20 weeks of feeding, obvious atherosclerotic plaques formed on the aortic roots of the mice, the intima was obviously thickened, macrophages under the intima were collected, and foam cells and fiber caps were further formed. You can see To it. The lesion became worse. HE staining showed obvious atherosclerotic plaque formation in the aortic root. Foam cells and lipid nuclei are obvious, fibrous caps are thin, macrophages aggregate locally, and the structure of vascular media is severely damaged. It is characterized by lipid erosion, atrophy and calcification, and fragile plaque. The model can also be fed a high-fat diet containing 2% cholesterol for 16 weeks. After 16 weeks, the serum lipid level increased, and the aortic sinus valve formed a typical atherosclerotic plaque, which contained a large number of foam cells. And coronary arteries.

  (2) Model characteristics After being fed a high-fat diet, ApoE gene-deficient mice formed obvious atherosclerotic plaques in the aortic roots and coronary arteries. The model animal ApoE gene-deficient mice has a clear genetic background and can be regenerated. Strength, lipid metabolism and humanoid plaque, small animal individual, low dose, easy to feed and manipulate. This is a whole animal model of experimental atherosclerosis suitable for screening anti-As drugs.

  (3) Comparative medicine ApoE gene-deficient mice can spontaneously develop hyperlipidemia and atherosclerosis. The total blood cholesterol level after modeling is 3-5 g/L, which is similar to the cholesterol level of human hyperlipidemia, but is usually used; the total cholesterol level of high-fat and hypercholesterolemia animals is 7-10 g/L. The development of atherosclerosis in model mice involves lipid streaks into mature plaques covered with fibrous caps.