老年恒河猴颈动脉粥样硬化性狭窄模型的建立

发布时间：2018-06-28 15:58

本文选题：颈动脉狭窄 + 动物模型　；参考：《广西医科大学》2013年硕士论文

【摘要】：目的本实验将通过使用球囊损伤联合高脂饲料喂养的方法,初步建立能够模拟人类由于动脉粥样硬化引起的颈动脉狭窄的老年恒河猴模型。为进一步研究人类颈动脉狭窄在缺血性脑血管病(ischemic cerebrovascular disease ICVD)的发生以及发展中的作用提供实验依据。方法4只体重相近的雄性老龄(15岁)恒河猴,随机分配为实验组和对照组,每组2只。采取股动脉穿刺的方法,使用球囊扩张损伤实验组动物左侧颈动脉(left carotid artery L-CA)中段,联合高脂饲料喂养14周,对照组仅使用基础饲料喂养。在喂养过程中,每2周对恒河猴进行神经系统功能的评分、称量体重及血脂水平的检测,每4周进行颈部血管的超声检查。14周后,再次进行全脑血管造影术,评价血管狭窄形成的情况,通过北美症状性颈动脉内膜剥脱术试验(american symptomatic carotid endarterectomy trial NASECT)法计算血管的狭窄率。结果 1.体重的变化：在喂养期间,实验组动物的体重随测量时间而变化,并且呈现出逐渐增长的趋势,与对照组的差异有统计学意义(P0.05)； 2.血脂水平的变化：在喂养期间,实验组的血清总胆固醇(serum total cholesterol TC),甘油三酯(triglyceride TG),载脂蛋白B (apolipoprotein B ApoB)及低密度脂蛋白胆固醇(low density lipoprotein cholesterol LDL-C)的含量随喂养时间而变化,并且呈显著的增高趋势,与对照组差异有统计学意义(P0.05)；而实验组的载脂蛋白A1(apolipoprotein A1ApoA1)和高密度脂蛋白胆固醇(high density lipoprotein cholesterol HDL-C)与对照组相比则没有明显的增高趋势(P0.05)； 3.神经系统功能评分的变化：14周的喂养时间内,所有实验动物神经系统功能评分始终为0分,未出现神经系统功能缺失。 4.颈动脉超声多普勒的结果：通过超声检查显示实验组损伤侧颈动脉中部出现动脉粥样硬化性改变：血流速度较前增快,收缩期血流速度(velocity during systole Vs)和舒张期血流速度(velocity during diastole Vd):猴1分别为135.6cm/s和24.8cm/s,猴2分别为141.6cm/s和36.4cm/s；管腔分别为1.8mm和1.6mm,较前减小；同时,还可以观察到内膜增厚,内-中膜厚度(intima-media thickness of artery IMT)为1.1mm和1.2mm。而实验组非损伤侧和对照组则接近正常。 5.复测全脑血管造影的结果：喂养结束后脑血管造影显示实验组L-CA直径分别为1.25mm和1.37mm, R-CA分别为2.38mm和2.41mm,通过计算左侧狭窄率分别为46.1%及45.8%,而对照组的左侧直径分别为2.33mm和2.35mm,右侧为2.42mm和2.39mm,没有狭窄形成。结论通过使用球囊扩张联合高脂饲料喂养的方法,可以初步地建立伴有体重和血脂水平增高的颈动脉粥样硬化性狭窄的恒河猴模型,超声及DSA检测可见颈动脉内有斑块形成、管腔狭窄。该模型能较好的模拟人类在高脂血症环境下所发生的颈动脉粥样硬化斑块的形成,为研究人类颈动脉狭窄在导致ICVD的发生以及疾病的进展过程中的作用提供了宝贵的实验依据。
[Abstract]:Objective the aim of this study is to establish an elderly Ganges RIver monkey model which can simulate human carotid stenosis caused by atherosclerosis by using balloon injury combined with high fat feed. To further study the occurrence and development of human carotid stenosis (ischemic cerebrovascular disease ICVD) in human carotid artery stenosis. The role of the exhibition provides experimental basis.
Methods 4 Ganges RIver monkeys, aged 15 years of age (15 years old), were randomly assigned to the experimental group and the control group, with 2 rats in each group. The left carotid artery (left carotid artery L-CA) in the balloon dilatation injury experimental group was fed with the middle part of the left carotid artery (artery L-CA), and the high fat diet was fed for 14 weeks, and the control group was fed with only basic feed. In the course, the neurological function of Ganges RIver monkeys was scored every 2 weeks, weighing the body weight and blood lipid level. After 4 weeks of cervical vascular ultrasound examination.14 weeks, the whole brain angiography was carried out again to evaluate the formation of vascular stenosis and through the North American symptomatic carotid artery intima exfoliation test (American Symptomatic Carotid end). Arterectomy trial NASECT method was used to calculate the stenosis rate of blood vessels.
Result
1. changes in weight: during the feeding period, the weight of the animals in the experimental group changed with the measured time, and showed a trend of gradual growth. There was a significant difference between the control group and the control group (P0.05).
2. changes in blood lipid level: during the feeding period, the serum total cholesterol (serum total cholesterol TC), triglyceride (triglyceride TG), apolipoprotein B (apolipoprotein B ApoB) and low density lipoprotein cholesterol (low density) were changed with feeding time, and increased significantly. There was a significant difference between the control group and the control group (P0.05), while the apolipoprotein A1 (apolipoprotein A1ApoA1) and the high density lipoprotein cholesterol (high density lipoprotein cholesterol HDL-C) in the experimental group were not significantly higher than those of the control group (P0.05).
3. changes in the function score of the nervous system: during the feeding time of 14 weeks, the neurological function score of all the experimental animals was always 0, and no nervous system dysfunction was found.
4. results of carotid ultrasound Doppler: ultrasound examination showed atherosclerotic changes in the central carotid artery in the experimental group: the blood flow velocity was faster than before, the systolic blood velocity (velocity during systole Vs) and the diastolic blood flow velocity (velocity during diastole Vd): monkey 1 were 135.6cm/s and 24.8cm/s, monkey 2, respectively. 141.6cm/s and 36.4cm/s, respectively, the lumen were 1.8mm and 1.6mm, respectively. At the same time, the intima thickening was observed, the thickness of the inner middle membrane (intima-media thickness of artery IMT) was 1.1mm and 1.2mm., while the non injury side and the control group were close to normal in the experimental group.
5. results of total cerebral angiography: after feeding, cerebral angiography showed that the diameter of L-CA in the experimental group was 1.25mm and 1.37mm, R-CA was 2.38mm and 2.41mm respectively. The left stenosis rate was 46.1% and 45.8%, respectively, while the left diameter of the control group was 2.33mm and 2.35mm, and the right was 2.42mm and 2.39mm, and no stenosis was formed.
Conclusion by using balloon dilatation combined with high fat feed, the Ganges RIver monkey model with carotid atherosclerotic stenosis with higher body weight and high blood lipid level can be initially established. Plaque formation and stenosis in the carotid artery can be detected by ultrasound and DSA. This model can better simulate human hair in hyperlipidemia environment. The formation of atherosclerotic carotid atherosclerotic plaques provides valuable experimental evidence for the study of the role of human carotid artery stenosis in the development of ICVD and the progress of the disease.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R-332;R543.4

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