吡格列酮降低动脉粥样硬化炎症和斑块破裂的PET/CT活体成像研究  

Plaque inflammation and plaque thrombosis are reduced by pioglitazone and are evaluated by fluorode-oxyglucose PET/CT in a rabbit model

作　　者：张明多[1] 闫云峰[1] 庄须翠[2] 张玉慧[2] 王争明 李德鹏 李丽琴 宋现涛[1] 吕树铮[1] 赵全明[2] ZHANG Mingduo;YAN Yunfeng;ZHUANG Xucui;ZHANG Yuhui;WANG Zhengming;LI Depeng;LI Liqin;SONG Xiantao;LV Shuzheng;ZHAO Quanming(Department of Cardiology,Beijing Anzhen Hospital,Capital Medical University,Belling Institute of Heart,Lung and Blood Vessel Diseases,Bering 100029,China)

机构地区：[1]首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所心内科一病房,100029 [2]首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所心内科二十一病房,100029 [3]中国人民解放军火箭军总医院PET/CT中心

出　　处：《心肺血管病杂志》2018年第8期789-795,共7页Journal of Cardiovascular and Pulmonary Diseases

基　　金：北京市自然科学基金面上项目(7132078)

摘　　要：目的:探讨吡格列酮对易损斑块的稳定作用及PET/CT活体成像特点。方法:所有实验动物随机分为吡格列酮组(n=10)和对照组(n=10)。采用球囊拉伤+间断高脂喂养的方法制造动脉粥样硬化模型。两组存活的实验动物于实验结束时进行药物激发试验。于实验中期及晚期检测血液学指标并进行两次PET/CT扫描。斑块破裂诱发试验后处死动物,取兔腹主动脉进行病理学分析。结果:吡格列酮组血清MMP-9,hs-CRP较对照组显著降低(P<0.05)。实验晚期吡格列酮组SUVmean值较基线值显著降低(P=0.008)。但对照组SUVmean值较基线值显著升高(P<0.000)。吡格列酮组斑块破裂率,斑块面积,巨噬细胞密度及新生血管计数显著低于对照组(P<0.05)。结论:吡格列酮可以通过降低斑块炎性程度以减少斑块破裂率。PET/CT可有效进行成像监测。Objective： We aimed at investigating the feasibility of PET/CT in monitoring the therapeutic effect of pioglitazone on plaque inflammation,and explore the underlying mechanisms of pioglitazone on reducing plaque vulnerability. Methods： 20 male New Zealand white rabbits were randomly divided into 2 groups： pioglitazone group（ n = 10） and control group（ n = 10） Atherosclerosis was induced in all rabbits by intermittent high-cholesterol diet and endothelial denudation. All survival rabbits at 18 wks underwent 2 pharmacological triggerings to induce plaque rupture. Blood was collected from 12 hours fasting animals at baseline and18 weeks after high-cholesterol diet. Rabbits underwent PET/CT scan twice： the first baseline scans and the second scans obtained at week 18 after drug triggering. After pharmacological triggering,all rabbits were euthanatized,and aortic histopathological analysis were performed. Results： Serum MMP-9,hs CRP and was lower in the pioglitazone group than in the atherosclerosis group（ P〈0.05 respectively） Treatment with pioglitazone significantly reduced SUVmean in the aorta of rabbits（ P = 0. 008）,However,there was a significant increase of SUVmean in rabbits fed with a cholesterol enriched diet alone（ P〈0.000） The incidence of plaque rupture,plaque area,macrophage density,and neovessels density was signicantly lower in pioglitazone than in control groups（ P〈0.05,respectively） Conclusion： Our study supports the hypothesis that pioglitazone can reduce incidence of plaque rupture by decreasing plaque inammation. 18 FDG-PET/CT can detect plaque inflammation and assess the effects of antiatherosclerotic drugs.

关 键 词：吡格列酮 PET/CT 动脉粥样硬化 血栓形成 兔 

分 类 号：R54[医药卫生—心血管疾病]