冠状动脉粥样硬化大鼠实验动物模型的改进与评价

目的通过对文献报道的动脉粥样硬化大鼠造模方法的改进,建立一种适合进行心血管疾病研究的冠状动脉粥样硬化Wistar大鼠模型。方法将40只大鼠随机分为对照组与模型组,对照组15只,模型组25只。模型组高脂饲料喂养配合前3个月,每月按15万U/kg每月腹腔注射维生素D3一次,对照组喂养普通饲料,造模时长150 d。实验结束后通过对血管内皮、脂代谢、炎症浸润几个方面对模型大鼠进行考察。结果证实模型组大鼠较对照组血清LDL-C、CHO、TG水平明显升高,HDL-C/LDL-C、NO/ET-1值明显降低;AI值显著增高;血清NO、ET-1、ox-LDL、AngⅡ、sICAM-1表达明显增高;HE染色显示：模型组大鼠冠状动脉出现血栓、内皮破坏、粥样斑块形成,血管壁钙化情况;心肌纤维组织增生,炎细胞浸润,心肌轻度变性;主动脉出现动脉粥样硬化斑块形成,而对照组无病变产生。结论本方法能够提供一种稳定的、复制性好的用于冠状动脉粥样硬化实验研究的大鼠模型。

Improvement and evaluation of rat models of coronary atherosclerosis

To improve the method of establishment of Wistar rat models of coronary atherosclerosist to serve research of cardiovascular diseases. Methods To overcome the resistance of Wistar rats to cholesterol-induced atherosclerosis,animals were given i. p. injection of vitamin D3 in a dose of 150000 IU monthly,for consecutive 3 months. Twentyfive rats were given cholesterol-enriched diet per month for first 3 months,followed by high cholesterol diet alone for 2months. Blood serum parameters were examined at days 0,30,90,120 and 150 days and histology of the coronary artery and aorta were examined at 120 and 150 days. Other 15 rats receiving a normal diet were used as a control group. Results Results of the experiment showed that in the model group,there were significant hypercholesterolemia,elevated serum LDL-C,CHO,and TG,decreased HDL-C / LDL-C andNO / ET- 1leves,increased AI value,significantly increased levels of serum NO,ET- 1,ox-LDL,AngII and sICAM- 1. Pathological examination showed thrombosis and endothelial damage,atherosclerotic plaques and calcification in the coronary artery wall,fibrosis,inflammatory cell infiltration and mild degeneration in the myocardium,and formation of atherosclerotic plaques in the aorta. No pathological alterations were found in the control group. Conclusions A stable and reproducible rat model of coronary arterial atherosclerosis is successfully established by our improved method. This animal model is more closely resembling atherosclerotic lesions in human alterations.