疾病动物模型,自发性冠状动脉硬化性心脏病动物模型 z-bio 2021-03-09 321

　　[Modeling mechanism] Watanabe rabbits with myocardial infarction are based on WHHL rabbits with a tendency to coronary atherosclerosis through continuous artificial selection of higher plasma cholesterol levels, severe coronary atherosclerotic lesions, and the main disease components are macrophages. Cells and foam cells are selected and bred from the progeny. Therefore, WHHLMI rabbits are more likely to develop severe coronary atherosclerosis in a relatively short period of time than WHHL rabbits, and eventually lead to coronary stenosis and myocardial infarction. Rabbits of WHHLMI strain begin to develop coronary atherosclerosis at the age of 2 months, and the incidence of myocardial infarction can reach 97% at the age of 30 months. The composition of coronary atherosclerotic lesions in WHHLMI rabbits is also different from that in WHHL rabbits. Coronary artery lesions in WHHLMI rabbits are mainly composed of foam cells and inflammatory cells, which are more unstable than those in WHHLMI rabbits, which are mainly composed of fibrous components. It is more likely to cause myocardial infarction.

　　【Modeling method】Hypercholesterolemia can occur when fed with ordinary feed, and coronary atherosclerosis can occur at 2 months of age. The incidence of coronary artery stenosis at 10 months and 20 months is 70% and 90%, respectively.

　　【Features of the model】After years of screening and breeding on WHHL rabbits with myocardial infarction prone, it is different from the coronary artery fibrosis of WHHL rabbits. The coronary artery plaques of WHHLMI rabbits are very similar to human vulnerable plaques. The typical lesion is composed of a large fat nucleus covered by a thin fibrous cap, which contains calcification points and a large number of macrophages. In addition, the pathological structure of the plaque also includes: hemorrhage in the plaque, calcified nodules, exfoliation of the endothelial layer and fibrous lesions. The cumulative incidence of myocardial infarction in WHHLMI rabbits reaches 97% at 30 months of age, and more than 90% of the myocardial infarction in WHHLMI rabbits is caused by coronary artery stenosis. When myocardial infarction occurs, ECG can be used to observe the ST-segment elevation in WHHLMI rabbits and humans, but the typical ECG changes are not completely consistent with the occurrence of myocardial infarction. Although severe coronary atherosclerosis in WHHLMI rabbits can cause coronary artery stenosis and myocardial infarction, typical plaque rupture is still not easy to observe in this animal model, which may be due to the lack of WHHLMI rabbits leading to vulnerable plaques Other factors of rupture, such as environment, psychological pressure, high blood pressure, etc.

　　[Model evaluation and application] WHHLMI rabbits can almost simulate the occurrence of human myocardial infarction. It is a powerful tool to study the formation of coronary atherosclerosis, myocardial ischemia, and myocardial infarction. It also provides new treatment methods and drug research. An animal model that is closer to humans. Plaque rupture and acute coronary syndrome may also be achieved in this animal model through the intervention of other intervention factors.