冠心病伴心外膜脂肪增厚大鼠模型的制备

Establishment of rat models of coronary atherosclerotic heart disease complicated with epicardial adipose tissue thickening

目的:建立冠心病(CAD)伴心外膜脂肪(EAT)增厚的SD大鼠模型,为研究EAT在CAD中的作用奠定基础。方法:50只雄性SD大鼠随机分为对照组(15只)和模型组(35只)。模型组大鼠高脂饲料喂养,从第0天开始,前3个月每月按20万U·kg-1腹腔注射维生素D3 1次;对照组大鼠喂养基本饲料,同步注射等量生理盐水,共造模210d。通过大鼠一般情况、体质量变化、血脂水平、EAT厚度和心肌组织病理表现等对模型大鼠进行评估。结果:与对照组比较,模型组大鼠皮毛黯淡,活动量少,喂饲90~180d时大鼠体质量增加速度减慢,180~210d时大鼠体质量逐渐降低,血清总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白(LDL-c)水平明显升高(P<0.05或P<0.01),高密度脂蛋白胆固醇(HDL-c)水平明显降低(P<0.05),动脉粥样硬化指数(AI)值明显升高(P<0.01),EAT明显增厚(P<0.05)。心肌组织病理形态表现,对照组大鼠冠状动脉内膜、中膜未见增厚,血管壁完整,未见血管狭窄,心肌间小血管未发现粥样斑块,内膜完整且未增厚;模型组大鼠冠状动脉出现内膜及中膜增厚,内皮破坏,大量粥样斑块形成,甚至钙化,冠脉狭窄85%以上,心肌间小血管内膜下可见大量泡沫细胞且内膜明显增厚。结论:成功复制SD大鼠CAD伴EAT增厚模型,该模型可用于EAT在CAD中病理生理及分子生物学等方面作用的研究。

Objective： To build the SD rat models of coronary atherosclerotic heart disease （CAD） complicated with epicardial adipose tissue （EAT） thickening, and to lay the foundation for the study on the role of EAT in CAD.Methods： Fifty healthy male SD rats were randomly divided into control group（n=15） and model group （n=35）. The rats in model group were fed with high fat diet; the rats were given i.p. injection of vitamin D3 in a dose of 200 000 IU·kg-1 monthly for consecutive 3 months, a total of 4 times. The rats in control group were administrated with the same volume of normal saline through the same route and were fed with normal diet. It took 210 d to build the models. The general condition, body weights, blood lipid levels, epicardial fat thickness and pathological changes of myocar clium tissue were detected.Results： The general condition showed that the hair of the rats in model group was shading and the activities were decreased.At 90-180 d, the body weights were slowly increased,and at 180-210 d, the body weights were gradually decreased. Compared with control group, the EAT thickness, the serum low-density lipoprotein cholesterol （LDL-c）, total cholesterol （TC）, triglyceride （TG） levels and atherosclerosis index（AI） of the rats in model group were significantly increased（P〈0.05 or P〈0.01）, while the high-density lipoprotein cholesterol （HDL-c） level was significantly decreased （P〈0.05 or P〈0.01）. No intima-media thickness and vascular stenosis of the coronary artery were found in control group and the vessel wall was complete. The atherosclerotic plaque and the intima thickness were not found in myocardial small vessel as well. However, the endothelial damage, inflammatory cell infiltration and lipid deposition, atherosclerotic plaques and calcification in the coronary artery wall of the rats in model group were found;the intima-media thickness was increased, coronary stenosis was above 85%, and a large number of foam cells were found in the intima which was thickened and damaged. Conclusion： The stable and reproducible SD rat models of CAD complicated with EAT thickening are successfully established, which can be used to study the role of EAT in the pathophysiology and molecular biology of CAD.