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

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.