机构地区:[1]河北大学附属医院心内科,河北省保定市071000 [2]首都医科大学附属北京安贞医院心内科,100029 [3]兰州大学第一临床医学院,730000
出 处:《中华内科杂志》2019年第11期808-813,共6页Chinese Journal of Internal Medicine
基 金:国家自然科学基金(81355392);河北省重点研发计划项目(18277755D);河北省财政厅、河北省卫生计生委2017年政府资助临床医学优秀人才培养和基础课题研究项目(冀财社[2017]46号)。
摘 要:目的应用正电子发射计算机断层扫描(PET-CT)对于在体炎症反应的敏感性,探讨运用该手段评估动脉粥样硬化斑块稳定性以及阿托伐他汀稳定斑块疗效的可能性。方法选取20只新西兰雄性大白兔采用抽签法随机分为阿托伐他汀干预组和对照组,每组10只。两组均给予高脂饮食喂养,2周后加胸腹主动脉球囊拉伤术制作动脉粥样硬化模型,术后继续髙脂饲养至第20周,其中阿托伐他汀干预组给予每日阿托伐他汀灌胃。第8周,实验兔行胸腹主动脉超声检查可见斑块提示20只兔均建模成功。第3周和第20周抽血检测血脂、高敏C反应蛋白(high sensitivity C-reactive protein,hs-CRP)及基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)。在第20周,存活实验动物(阿托伐他汀干预组9只,对照组7只)进行氟标记的脱氧葡萄糖(18F-FDG)PET-CT扫描,测量主动脉段的平均标准化摄取值(meanstandardized uptake value,SUVmean)和最大标准化摄取值(maximum standardized uptake value,SUVmax),处死动物,主动脉标本行免疫组化,测量并比较分析病理学指标。结果第20周,阿托伐他汀干预组血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)均低于对照组,且hs-CRP[(4.58±0.51)ng/ml比(5.87±0.66)ng/ml,P<0.01]、MMP-9[(43.93±2.16)ng/ml比(50.77±2.32)ng/ml,P<0.01]、SUVmean(0.59±0.15比0.68±0.20,P<0.05)、SUVmax(0.68±0.20比0.81±0.27,P<0.05)及斑块面积[(0.36±0.24)mm^2比(0.50±0.34)mm^2,P<0.05]、巨噬细胞密度值[(4.34±1.54)%比(5.65±1.89)%,P<0.01]均低于对照组,差异有统计学意义。阿托伐他汀干预组斑块纤维帽厚度高于对照组[(4.12±0.66)μm比(2.96±0.37)μm],差异有统计学意义(P<0.01)。对应动脉段斑块面积与SUVmean(r=0.27,P<0.05)、SUVmax(r=0.43,P<0.01)呈正相关;纤维帽厚度与SUVmean(r=-0.38,P<0.05)、SUVmax(r=-0.47,P<0.01)呈负相关;巨噬细胞密度值与SUVmean(r=0.52,P<0.01)、SUVmax(r=0.51,P<0.01)呈正相关。结论应用Objective Positron emission tomography-computed tomography(PET-CT)has been used to quantify inflammatory response in the body.The aim of the present study was to explore the possibility of using this method to evaluate the stability of atherosclerotic plaques and the efficacy of atorvastatin in stabilizing atherosclerotic plaques.Methods Twenty New Zealand male white rabbits were included and divided into the atorvastatin intervention group and the control group,with 10 rabbits in each group.Rabbits in both groups were fed with a high fat diet for 20 weeks,and treated with thoracoabdominal aortic balloon-pulling to establish atherosclerosis model at the end of the 2nd week.Rabbits in atorvastatin intervention group was given atorvastatin intragastrically once a day.At the 8th week,thoracoabdominal aortic ultrasound was used to detect plaques in all rabbits.Blood was drawn at the 3rd and the 20th week,respectively,to measure blood lipids,high-sensitive C-reactive protein(hs-CRP)and matrix metalloproteinase-9(MMP-9).At the end of experiment,survival animals were scanned by 18F-FDG PET-CT,and the average and maximum standard uptake values(SUVmean,SUVmax)of aortic segments were measured.Thereafter,the animals were sacrificed and aortic specimens of rabbits were taken and examined by immunohistochemistry.The pathological indexes were measured and compared.Results At the end of experiment,the total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),hs-CRP[(4.58±0.51)ng/ml vs.(5.87±0.66)ng/ml,P<0.01],MMP-9[(43.93±2.16)ng/ml vs.(50.77±2.32)ng/ml,P<0.01],SUVmean(0.59±0.15 vs.0.68±0.20,P<0.05),SUVmax(0.68±0.20 vs.0.81±0.27,P<0.05),plaque area[(0.36±0.24)mm^2 vs.(0.50±0.34)mm^2,P<0.05]and density of macrophage[(4.34±1.54)% vs.(5.65±1.89)%,P<0.01]in the atorvastatin intervention group were significantly lower than those in the control group.In contrast,fiber cap thickness of the plaque[(4.12±0.66)μm vs.(2.96±0.37)μm,P<0.01]in the atorvastatin intervention group was higher than that of
关 键 词:动脉粥样硬化 阿托伐他汀 氟脱氧葡萄糖正电子发射计算机断层扫描 兔
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