目的建立兔实验性动脉粥样硬化和心肌梗死双模型,比较血管新生在动脉粥样硬化和缺血心肌中发生机制的差异。方法选择20只雄性新西兰兔,随机分为两组,A组10只为普通饮食对照组,B组10只为高脂饮食组,共喂养9周。第3周末心导管封堵冠状动脉血管致急性心肌梗死。测定不同时期血脂水平。实验终点,苏丹Ⅲ染色测定主动脉斑块阳性面积;免疫组化染色测定不同心肌区域和主动脉血管壁CD34阳性反应强度,测定不同心肌区域新生血管密度;Western blot检测hypoxia-inducible factor1α(HIF-1α)在动脉粥样硬化和缺血心肌中的表达。结果高脂组血脂水平进行性增高。高脂组主动脉斑块阳性面积高于对照组,差异有显著性。在心肌正常区、梗死区和梗死边缘区:CD34阳性反应强度和新生血管密度各组间差异有显著性,HIF-1α的表达各组间差异有显著性;均为梗死边缘区最高,梗死区次之,正常区最低。在高脂组和对照组主动脉:CD34阳性反应强度两组间差异有显著性,HIF-1α的表达两组间差异有显著性;高脂组强于对照组。结论成功建立兔实验性动脉粥样硬化和心肌梗死双模型,提示动脉粥样硬化和缺血心肌中均有血管新生的参与。
Objective To establish a model of atherosclerosis and acute myocardial infarction in rabbit,and compare the role of angiogenesis in the pathogenetic mechanisms of atherosclerosis and ischemic myocardium. Methods A total of 20 male New Zealand white rabbits were randomly divided into 2 groups equally. Group A was fed with the high fat diet for 9 weeks; Group B was fed with the full diet. At the end of the third week,acute myocardial infarction was produced by using the interventional method of cardiac catheter. The changes of blood lipid were observed at different time points. At the end of experiment,the plaque positive area in aortic arch was determined by Sudan Ⅲ staining. The CD34 positive response intensity of myocardium and aortic wall, and the capillary density of myocardium were measured by immunohistochemical staining. The expression of HIF-1α was detected in both atherosclerosis and ischemic myocardium by Western blot. Results The level of blood lipid in group A was raising gradually. The plaque positive area of group A was significantly increased than that in the group B ( P〈0. 01 ). In the areas of the normal,infarction and marginal zone: the CD34 positive response intensity and the capillary density of myocardium had a significant difference(P〈0. 01 ). The expression of HIF-1α also had a significant difference,just as the marginal zone of infarction the infraction area the normal area. In the aortic walls of groups A and B,the CD34 positive response intensity had a significant difference( P〈0. 01). The expression of HIF-1α also had a significant difference,higher in the group A than in the group B. Conclusion An original rabbit model of atherosclerosis and acute myocardial infarction has been successfully established. Angiogenesis is present not only in artherosclerosis but also in ischemic myocardium.