适配体介导的MRI-As靶向造影剂的动物体内实验

Animal experiment of aptamer mediated MRI-As targeting contrast agent in vivo

目的合成一种靶向于动脉粥样硬化（As）病变的核磁共振成像（MRI）纳米造影剂,为开发新型动脉粥样硬化MRI诊断技术提供实验依据。方法运用自主研发的对泡沫细胞具有靶向性的寡合苷酸适配体PM1,与四氧化三铁（Fe_3O_4）纳米粒耦联,制备出具有靶向作用的MRI造影剂,命名为MRI-As。用高脂饲料饲养建立载脂蛋白E基因敲除（ApoE^（-/-））小鼠As动物模型,苏丹红Ⅳ染色鉴定主动脉As病变。MRI成像仪检测MRI-As造影剂对As小鼠斑块MRI成像的影响。结果 ApoE^（-/-）小鼠模型动物MRI显像可以观察到主动脉壁毛糙,As病灶呈高信号亮点,与周围组织形成良好对比,中心信号较高,较均匀,边缘较清楚。注射MRI-As造影剂后,As病变区信号强度呈下降趋势,管壁不光滑,呈多发斑点状信号的缺损。对照组动物注射MRI-As造影剂后,血管壁信号强度无明显变化。结论 MRI-As造影剂对As病变能起到主动靶向作用,利用Fe_3O_4纳米粒对As病变的阴性对比效果,显著提高了As病变的MRI图像分辨率,具有As MRI影像的新型、快速、高效、无创、无辐射造影剂的潜质。

Aim To synthetize a nuclear magnetic resonance imaging（ MRI） nano contrast agent targeted to atherosclerosis（ As） lesions,and to provide experimental evidence for the development of a new MRI diagnostic technique for As. Methods The self developed aptamer PM1,which was targeted to the foam cells,was coupled to iron oxide（ Fe_3O_4） nanoparticles,and the target MRI contrast agent was prepared,named MRI-As. The As animal model of apolipoprotein E gene knockout（ ApoE^（-/-）） was established by feeding with high-fat diet. The As lesion of aorta was identified by Sudan red Ⅳ staining. Effect of MRI-As contrast agent on MRI imaging of plaque in As mice was detected by MRI imager. Results MRI imaging of the ApoE^（-/-）mice animal model showed that the aortic wall was rough. As lesions showed high signal intensity,which was well contrasted with the surrounding tissues. The central signal was higher,more uniform and the edge was clearer. After injection of MRI-As contrast agent,the signal intensity of As lesion area showed a downward trend,and the vascular wall was not smooth and showed the defect of multiple spot signal. After injection of MRI-As contrast agent in control group,the signal intensity of vascular wall did not change significantly. Conclusions MRI-As contrast agent can play an active targeting to As lesions. Using the negative contrast effect of Fe_3O_4 nanoparticles on As lesions,MRI-As contrast agent significantly enhances the resolution of the MRI image of As lesion,and it has the potential of new,fast,efficient,non-invasive,non radiative contrast agent for As MRI image.