冠状动脉粥样硬化大鼠实验动物模型的改进与评价
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基金项目:中国中医科学院自主选题“中医治疗冠心病能力建设”(项目编号:ZZ080401)

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    目的:本研究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天。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:通过改进后,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。

    Abstract:

    This research builds the improved method of atherosclerosis rats mold based on the literature, which aims to establish a suitable coronary heart disease wistar rats model for cardiovascular research. To overcome the wistar rats’s resistance to cholesterol induce atherosclerosis, animals were given D3 vitamin at 150000 IU :rat per month associated with cholesterol-enriched diet for first 3 months, following 2 months of high cholesterol diet alone. Blood serum parameters (at days 0,30,90,120 and 150) and coronary artery, aortic and heart morphology (at days 120 and 150)were examined. Other animals receiving a normal diet were used as a control group. Results showed that at day 90 severe hypercholesterolemia, elevated blood serum LDL-C and CHO, oxidized LDL, AngⅡ,sICAM-1.Lesions were characterized by widening of the first interlamellar spaces in the aorta, fibrosis of coronary arterial arterial wall and recent foci of myocardial fibrosis. At day 150d oxidized LDL, AngⅡ,sICAM-1 and ET-1were more enhanced. The D3 vitamin administration induced advanced atherosclerotic lesions in arterial wall, represented by the rupture of elastic lamellae, smooth muscle cell proliferation and lipid-calcic core. The complicated plaque frequently evolved into ulcerations. The ischaemic effects were represented by acute myocardial infarction. D3 vitamin is an atherogenic agent which, when associated with hypercholesterolemia, allows the development of advanced atherosclerotic lesions in wistar rat which resembles human plaque.

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李同达,李冬梅,徐慧,宗文静,曹洪欣.冠状动脉粥样硬化大鼠实验动物模型的改进与评价[J].中国实验动物学报,2013,21(6).

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  • 收稿日期:2013-07-03
  • 最后修改日期:2013-07-23
  • 录用日期:2013-07-29
  • 在线发布日期: 2014-01-02
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