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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 To investigate the effect of oxidized low density lipoprotein (oxLDL) targeted ultramicro - superparamagnetic iron oxide nanoparticles (USPIO) on MR imaging of atherosclerosis in apolipoprotein E knock - out mice (ApoE - / - In the role. Methods Polyethylene glycol (PEG) coated USPIO was conjugated with anti-mouse oxLDL antibody to construct anti-oxLDL-USPIO targeting probe. Non-specific IgG-USPIO and pure USPIO as a control. The physical and specific characteristics of the probes were analyzed by transmission electron microscopy (TEM), dynamic light scattering (DLS) and indirect enzyme linked immunosorbent assay (ELISA). The apoE - / - carotid cannulation model was used in animal models.ApoE - / - mice were injected with 30mg Fe / Kg into the caudal vein for MR imaging at 8h and 24h after injection. Results The signal of carotid atherosclerotic plaque in MRP2WI was decreased in ApoE - / - mice via tail vein injection for 8h and 24h, and the reduction rate of plaque signal was -30.4 ± 16% at 8h and 24h respectively. 34.7 ± 19%. The signals of carotid atherosclerotic plaque in non-specific IgG-USPIO group, pure USPIO group and competitive inhibition group were slightly decreased, which were significantly different from those of the targeted probe group (P <0.05). Immunohistochemistry confirmed anti-oxLDL-USPIO labeling rate and oxLDL, CD68 expression was positively correlated. Conclusions Anti-oxLDL-USPIO can show the changes of carotid atherosclerotic plaque in apoE - / - mice within 24h and can specifically display the distribution of oxLDL in carotid atherosclerotic plaque, which can be used for the treatment of carotid artery Evaluation of atherosclerotic plaque.