动脉粥样硬化斑块OxLDL靶向的MR分子影像学实验研究  

OxLDL-targeted iron oxide particles for magnetic resonance detection of carotid atherosclerotic lesions in vivo

作　　者：付明翠[1] 文颂[1] 卢瞳[1] 柳东芳[1] 周官辉[1] 安艳丽[1] 廖蕾[1] 居胜红[1] 滕皋军[1] 

机构地区：[1]东南大学附属中大医院放射科,江苏南京210009

出　　处：《磁共振成像》2011年第5期331-336,共6页Chinese Journal of Magnetic Resonance Imaging

基　　金：国家自然基金国际合作交流项目资助(项目编号:30910091)

摘　　要：目的研究氧化低密度脂蛋白(oxLDL)靶向的超微超顺磁性纳米氧化铁(USPIO)探针在载脂蛋白E基因敲除小鼠(ApoE-/-)颈动脉动脉粥样硬化MR成像中的作用。方法将聚乙二醇(PEG)包被的USPIO与抗小鼠oxLDL抗体结合,构建anti-oxLDL-USPIO靶向探针。以非特异性IgG-USPIO及单纯USPIO作为对照。应用透射电镜(TEM)、动态光散射法(DLS)、酶联免疫吸附间接法(ELISA)分析探针的物理及特异性特征。动物模型使用apoE-/-颈动脉套管模型.ApoE-/-小鼠尾静脉注入30mgFe/Kg后,分别于注药前、注药后8h及24h进行MR成像。结果 ApoE-/-小鼠经尾静脉注入靶向探针8h及24h后,在MRT2WI上颈动脉粥样硬化斑块信号减低,8h、24h斑块信号减低率分别达到-30.4±16%、-34.7±19%,非特异性IgG-USPIO、单纯USPIO组及竞争性抑制组颈动脉粥样硬化斑块信号轻度降低,与靶向探针组比较有统计学差异,P<0.05。免疫组化证实anti-oxLDL-USPIO标记率与oxLDL、CD68表达呈正相关。结论 Anti-oxLDL-USPIO可以在24h内显示apoE-/-小鼠颈动脉粥样硬化斑块信号改变,可以特异性显示颈动脉粥样硬化斑块内的oxLDL分布,可用于药物治疗后颈动脉粥样硬化斑块的评价。Objective： The aim of this study was to determine the role of oxLDL targeted iron oxide particles in atherosclerotic lesions imaging in carotid atherosclerosis lesions of apoE-/- mice. Materials and Methods： PEG coated USPIO was conjugated with anti-mouse-oxLDL antibodies to construct an anti-oxLDL- USPIO probe while IgG-USPIO and unconjugated USPIO was used as controls. All formulations were characterized by using TEM, DLS and ELISA. The model of perivascular collar in the left carotid in apoE-/- mice was used. The MRI was processed in pre-, 8 h and 24 h after tain vein injection of a 30 mg Fe/Kg dose of USPIO nanoparticles. Results： MRI ofatherosclerotie lesion, as manifested by signal loss, was observed after administration of targeted USPIO at 8 h and 24 h, the percent of signal reduced was -30.4±16% and -34.7±19% while the IgG-USPIO, pure USPIO and inhibition group have limited signal reduction, the difference was significant, p〈0.05. Immunohistoehemistry confirmed the presence of oxLDL/CD68 and iron particles. Conclusion： This study demonstrates that anti-oxLDL-USPIO can be used in imaging atherosclerotic lesions within 24 hours. It suggests a clinically translatable platform for the detection of oxLDL in atherosclerotic plaque in vivo and will play a role in therapeutic evaluation of atherosclerotic carotid plaque.

关 键 词：动脉粥样硬化 抗体 OXLDL 磁共振成像 

分 类 号：R445.2[医药卫生—影像医学与核医学] R543.4[医药卫生—诊断学]