兔颈总动脉粥样硬化易损斑块模型的建立及PET成像初步研究

发布时间：2018-01-21 18:30

本文关键词： 动物模型颈总动脉粥样硬化易损斑块内膜面积放射性核素显像　出处：《苏州大学》2009年硕士论文　论文类型：学位论文

【摘要】： 目的:一、通过介入球囊损伤联合高脂饮食建立兔颈总动脉粥样硬化易损斑块模型。二、利用正电子发射计算机断层显像仪(PET)检测斑块内巨噬细胞对~(18)F-FDG的摄取,并与病理结果进行对照研究,评价PET无创检测颈总动脉粥样硬化易损斑块的价值。材料与方法: 一、建立动物模型:18只新西兰大白兔随机分成实验组(15只)和对照组(3只)。两组动物首先高脂饲料(含2%胆固醇)适应性喂养1周,其后实验组经右侧股动脉入路使用不可脱球囊损伤右侧颈总动脉中段,并饲喂相同的高脂饲料16周;对照组继续单纯饲喂相同的高脂饲料16周。二、数字减影血管造影(DSA)检查:实验组于球囊损伤后16周经左侧股动脉入路行颈总动脉数字减影血管造影,检测血管狭窄情况(血管狭窄度＞30%、狭窄段长度＞1.0cm为建模成功必要条件);对照组同期进行血管造影检查。三、正电子发射计算机断层显像(PET)检查:双侧颈总动脉CTA检查,明确血管解剖位置。静脉注射~(18)F-FDG(1.0mCi/kg)180min后,两组动物行双侧颈总动脉PET显像,检测右侧颈总动脉粥样硬化斑块层面双侧颈总动脉感兴趣区(ROI)的最大标准化摄取值(SUVmax),计算靶/非靶摄取比值(T/NT)。四、血脂测定:实验组动物分别于高脂喂养前、球囊损伤后即刻和球囊损伤后16周这3个时间点测定血脂水平。对照组与实验组在相同时间点检测血脂。五、病理检查:处死实验动物,分离实验侧颈总动脉靶区和对照侧及对照组颈总动脉中段,常规HE染色,计算血管内膜的面积。实验组双侧颈总动脉血管内膜面积与PET检查获得的SUVmax进行相关分析。结果: 一、本实验成功建立10只兔颈总动脉中段粥样硬化易损斑块模型,建模成功率为66.7%(10/15)。实验组动物1只死于感染,4只动物右侧颈总动脉血管造影不符合本实验血管狭窄条件的要求。二、数字减影血管造影(DSA)检查:实验组右侧颈总动脉血管造影显示为显著的偏心性狭窄,平均狭窄率为(59.57±17.51)%,实验组左侧颈总动脉及对照组双侧颈总动脉血管未见狭窄。三、正电子发射计算机断层显像(PET)检查:实验组兔右侧颈总动脉靶区SUVmax显著高于左侧相应区域(右侧SUVmax:0.82±0.42,左侧SUVmax:0.66±0.38,T/NT=1.62:1),配对样本的t检验显示实验组双侧颈总动脉SUVmax具有显著差异(t=2.927,v=59,P＜0.05)。对照组双侧颈总动脉相应区域SUVmax无显著差异(右侧SUVmax:0.59±0.13,左侧SUVmax:0.62±0.20)。四、血脂检测:高脂喂养后,实验组与对照组的血脂浓度无明显差异。五、病理检查:实验组右侧颈总动脉靶区病理染色表现符合动脉粥样硬化易损斑块的病理学特征表现,其内可见广泛分布的巨噬细胞及其形成的泡沫细胞,血管内膜明显增厚。动脉粥样硬化斑块内膜面积和PET检查SUVmax具有正相关关系(r=0.443,P＜0.05)。结论: 一、采用3mm球囊介入扩张新西兰大白兔颈总动脉中段联合高脂饮食可以建立兔颈总动脉粥样硬化易损斑块模型,建模成功率较高。二、~(18)F-FDG PET无创检测动脉粥样斑块的稳定性具有一定的可行性。这种非侵入性的影像技术有可能在临床上用作动脉粥样斑块导致缺血性脑血管病的风险评估。
[Abstract]:Objective: to establish a rabbit carotid atherosclerotic plaque model by interventional balloon injury combined with high fat diet.
Two, we detected the uptake of ~ (18) F-FDG in plaque by positron emission computed tomography (PET) and compared with pathological findings, and evaluated the value of PET in non-invasive detection of vulnerable plaques of carotid atherosclerosis.
Materials and methods:
An animal model: 18 rabbits were randomly divided into experimental group (15 rats) and control group (3). Two groups of animal first high fat diet (containing 2% cholesterol) fed for 1 weeks, then the experimental group through the right femoral artery approach using detachable balloon injury in the right carotid artery the same, and fed with high fat diet for 16 weeks; the control group to continue feeding the same high-fat diet for 16 weeks.
Two, digital subtraction angiography (DSA) examination: in the experimental group 16 weeks after balloon injury of the left femoral artery approach for carotid artery DSA, vascular stenosis (stenosis degree of stenosis length > 30%, > 1.0cm for modeling the necessity of success); the control group at the same time of angiography.
Three, positron emission tomography (PET) examination: bilateral carotid artery CTA examination, clear vascular anatomy. Intravenous injection of ~ (18) F-FDG (1.0mCi/kg) 180min, two groups of animal by bilateral carotid artery PET imaging detection of right carotid atherosclerotic plaque level bilateral carotid artery region of interest (ROI) the maximum standard uptake value (SUVmax), calculate the target / non target uptake ratio (T/NT).
Four, blood lipid determination: the experimental group animals were measured before and after 16 weeks of balloon injury and 3 weeks after the high fat diet. The blood lipid level was detected at the same time points in the control group and the experimental group at the same time point.
Five, pathological examination: the experimental animals were sacrificed, the common carotid artery target area and the control group were separated from the experimental common carotid artery, and the area of intima was calculated by routine HE staining. The intimal area of bilateral common carotid artery in the experimental group was correlated with the SUVmax obtained by PET.
Result:
First, the atherosclerotic plaque models of 10 rabbits were successfully established in this experiment. The success rate of atheromatous plaque was 66.7% (10/15). 1 of the animals in the experimental group died of infection. The right common carotid artery angiography in 4 animals did not meet the requirements of the experimental vascular stenosis.
Two, digital subtraction angiography (DSA): in the experimental group, the right carotid artery angiography showed a significant eccentric stenosis, with an average stenosis rate of (59.57 + 17.51)%. There was no stenosis in both the left common carotid artery and the control group.
Three, positron emission tomography (PET) examination: the right carotid artery of rabbits in group SUVmax were significantly higher than that of the corresponding target area (left right left SUVmax:0.82 + 0.42, SUVmax:0.66 + 0.38, T/NT=1.62:1), paired samples t test showed that the experimental group of bilateral carotid artery SUVmax with significant difference (t=2.927, v=59, P. "0.05). The control group of bilateral common carotid arteries of the corresponding region of SUVmax had no significant difference (right SUVmax:0.59 left SUVmax:0.62 + 0.13, + 0.20).
Four, blood lipid test: after high fat feeding, there was no significant difference in the blood lipid concentration between the experimental group and the control group.
Five, pathological examination: the experimental group of right carotid artery pathological staining pathology with target vulnerable atherosclerotic plaque characteristics, widely distributed in the macrophages and the formation of foam cells, intimal thickening. Atherosclerotic plaque intima area and PET examination of SUVmax had a positive correlation (r=0.443, P < 0.05).
Conclusion:
First, using 3mm balloon intervention to expand the middle common carotid artery and high fat diet of New Zealand white rabbits can establish a rabbit carotid atherosclerosis vulnerable plaque model, and the successful rate of modeling is high.
Two, ~ (18) F-FDG PET is feasible for non-invasive detection of atherosclerotic plaque stability. This non-invasive imaging technology may be used as a risk assessment for ischemic cerebrovascular disease in atherosclerotic plaque clinically.

【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2009
【分类号】：R-332;R817

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