动物造模,药效评价,动脉粥样硬化 z-bio 2024-09-19 620

　　(1) Method of replication: Male Wistar rats weighing 180-200g were intraperitoneally injected with 600000 U/kg body weight of vitamin D at once; And feed with basic feed. After injecting vitamin D for 34 days, the animals were anesthetized with pentobarbital sodium and infused with 300ml of 1% paraformaldehyde and 1.25% glutaraldehyde solution through left ventricular catheterization. Immediately, the aorta was taken for paraffin sectioning, HE staining, and ultra-thin sectioning, and observed under light and electron microscopy. The smooth muscle cells in the aortic wall of animals proliferate obviously, the cells are arranged in disorder, and the structure of the elastic fiber layer is unclear. The local wall protrudes into the lumen, forming a typical arteriosclerotic plaque. Under the electron microscope, collagen fibers proliferate under the aortic endothelium. There are a large number of collagen fibers between smooth muscle cells, and foam cells can be seen under the endothelium. Another method is to administer 400000 U/kg body weight of vitamin D by gavage at 0, 24, and 48 hours, followed by feeding with standard feed. After 9 weeks of oral administration of 400000 U of vitamin D, arterial sections showed signs of media edema and calcification, media smooth muscle hyperplasia, intimal injury, and subendometrial calcification.

　　(2) Model characteristics One time intraperitoneal injection of vitamin D to induce atherosclerosis model Compared with the previous use of vitamin D to feed animals to induce atherosclerosis, it has simpler operation, lower cost, shorter time and higher success rate. This model has broad application prospects for the pathogenesis of As and the evaluation of drug efficacy.

　　(3) There have been reports on the formation of arterial wall damage and sclerosis induced by vitamin D in comparative medicine for a long time. In this animal model, smooth muscle hyperplasia, internal elastic membrane rupture and collagen fiber increase occurred on the 18th day. On the 34th day, smooth muscle cells extended from the rupture of the internal elastic membrane, and some smooth muscle cells became foam cells. The whole pathological change process was similar to that of As, and was basically consistent with the pathological change process induced by cholesterol and other high-fat foods in the past. Previous studies have shown that the level of calcium content in the coronary artery wall is closely related to the formation of lipid streaks, fibrous plaques, and late stage complex plaques in the coronary artery wall. This model establishes the As model through the method of calcium overload. High doses of vitamins can cause arterial calcification, which in turn affects lipid absorption and blood lipid levels; Vitamin D can also induce damage to the integrity of the arterial wall endothelium, which is beneficial for plasma lipids to invade and damage the wall, leading to arteriosclerosis.