动物造模,药效评价,动脉粥样硬化 z-bio 2024-09-19 379

　　(1) Method of replication: Experimental macaques aged 10-16 years old were intravenously injected with 50-75mg/kg adrenaline once a week and fed with high-fat feed containing 1% cholesterol for 6 consecutive months. After stopping adrenaline, 10mg of methylthiouracil was added to every 150g of feed for a total of 16-17 months of modeling. After the modeling is completed, the animal is anesthetized and the chest is opened. First, 2ml of heparin and 1% sodium nitrite are injected into the heart. The left ventricular aorta is intubated, and the left atrium is cut open. Under a pressure of 14.7-18.7kPa, 37 ℃ physiological saline is rapidly perfused first, followed by a mixture of 4 ℃ 2% formaldehyde and 2.5% glutaraldehyde fixative (250ml/kg body weight). Craniotomy is performed to extract the brain, and bilateral middle cerebral arteries and their branches located 0.5-1.5cm from the starting point are taken. After modeling, the large and medium-sized extracranial arteries of the animals could see dense porridge spots. The mitochondria and endoplasmic reticulum of the endothelial cells of the middle cerebral artery were expanded, the gap was widened, the intima was locally thickened, and the number of smooth muscle cells in the intima was increased. Occasionally, the endothelium was partially broken, monocytes adhered, the internal elastic membrane was complete, the protrusions of the smooth muscle cells in the middle membrane were increased, and the organelles were rich, showing "secretory" changes, and the stroma was increased. Localized thickening of the intima of the central branch, accompanied by endothelial rupture. If an elderly monkey aged 16 months to 2 years is used for modeling, the same method can also be used for modeling after 22 to 23 months.

　　(2) Model features: This model is modeled using primate macaques and fed a high-fat diet for 16-28 months. Compared with other animal models, its cardiovascular anatomy and physiological functions are closer to those of humans, but the modeling time is longer.

　　(3) Comparative Medicine This model takes rhesus monkey as the model animal. The pathological changes of the middle cerebral artery after modeling are consistent with the early changes of human atherosclerosis. The results of the changes in the ultrastructure of the central branch also show the morphological signs of progressive changes of atherosclerosis. The elderly monkeys show that the middle cerebral artery, the highly heterotypic smooth muscle cells of the central branch and a large number of collagen fibers produced by them increase the arterial stiffness, which is consistent with the pathological changes of the elderly cerebral artery atherosclerosis seen in clinical.