靶向USPIO分子探针联合MR监测动脉粥样硬化细胞间黏附分子-1变化  

Monitoring the changes of atherosclerosis intercellular adhesion molecule-1 by targeting ultra-miniature superparamagnetic iron oxides molecular probe combined with magnetic resonance

作　　者：孙明霞 冯越[1] 谢敏 韩玉鑫 Sun Mingxia;Feng Yue;Xie min;Han Yuxin(Departmen of Radiology,Zhejiang Hospital,Hangzhou 310013;Sailan Biological Technology(Hangzhou)Limited Company,Hangzhou 310052,China;Sir Run Shaw Hospital Affiliated to Zhejiang University Medical College,Hangzhou 310016,China)

机构地区：[1]浙江医院放射科,杭州310013 [2]浙江杭州赛澜生物技术有限公司,310052 [3]浙江大学医学院附属邵逸夫医院,杭州310016

出　　处：《心脑血管病防治》2020年第4期348-351,共4页CARDIO-CEREBROVASCULAR DISEASE PREVENTION AND TREATMENT

基　　金：浙江省自然科学基金(LY15H180009)。

摘　　要：目的制备细胞间黏附分子-1(ICAM-1)靶向超微型超顺磁性氧化铁颗粒(USPIO)分子探针并联合磁共振(MR)研究动脉粥样硬化中ICAM-1的变化。方法通过水浴法将聚乙二醇(PEG)包被的USPIO和ICAM-1抗体合成ICAM-1靶向USPIO分子探针。通过透射电镜、动态光散射、酶联免疫吸附间接法检测分子探针的理化特性。使用ApoE基因敲除雄性小鼠建立动脉粥样硬化斑块模型后进行常规MR及增强MR扫描。分别注射ICAM-1靶向USPIO、非特异性IgG-USPIO分子探针,注药前及注药后0.5 h、2 h进行MR横断位扫描。MR扫描完成后进行病理学检查、免疫组织化学染色及电镜检查。结果磁共振扫描显示:靶向探针组增强后,粥样硬化斑块处信号明显减低。靶向探针组及非特异性IgG-USPIO组增强前、增强后0.5 h、2 h平均相对信号强度(rSI)有统计学意义(F=55.988,P<0.01);非特异性IgG-USPIO探针组增强后斑块信号轻度降低,增强后0.5 h、2 h rSI与靶向分子探针组比较均有统计学意义(t=-2.403、-3.147,P<0.05)。电镜检查显示:靶向探针组增强后铁颗粒在动脉粥样硬化斑块处较多沉积,非特异性IgG-USPIO探针组增强后铁颗粒在内皮下组织内有较多沉积。结论ICAM-1在粥样硬化进程中具有空间效应,结合MR可作为动脉粥样硬化发生和发展的指标。Objective To prepare ultra-miniature superparamagnetic iron oxides(USPIO)probe targeted by intercellular adhesion molecule-1(ICAM-1)and study the changes of ICAM-1 in atherosclerosis with magnetic resonance(MR).Methods ICAM-1 targeting USPIO probe was synthesized from polyethylene glycol(PEG)coated USPIO and ICAM-1 antibodies by water bath method.The physicochemical property of molecular probe was detected by transmission electron microscope(TEM),dynamic light scattering(DLS)and enzyme-linked immunosorbent assay(ELISA).The model of atherosclerotic plaque in ApoE gene knockout mice was used.All animals underwent routine and enhanced MR scanning after anesthesia.ICAM-1 targeted USPIO and non-specificity IgG-USPIO molecular probes were injected respectively.MR transverse scanning was performed before injection and at 0.5 h and 2 h after injection.After MR scanning,pathological examination,immunohistochemical staining and electron microscopic examination were performed.Results Magnetic resonance imaging showed that the signal of atherosclerotic plaque in the targeted USPIO group was significantly decreased after enhancement of ICAM-1 targeted USPIO molecular probe,average relative signal strength(rSI)of 0.5 h and 2 h before and after enhancement was statistically significant between targeted USPIO group and non-specificity IgG-USPIO group(F=55.988,P<0.01).While the signal of atherosclerotic plaque decreased mildly in non-specificity IgG-USPIO group,the difference was significant between non-specificity IgG-USPIO group and targeted group at 0.5 h and 2 h after enhancement(t=-2.403,-3.147,P<0.05).Electron microscopic examination showed that iron particles were deposited in plaque of targeted USPIO group after enhanced,while non-specificity IgG-USPIO group deposited in subendothelial tissues.Conclusion ICAM-1 has spatial effect in the process of atherosclerosis and can be used as an index to monitor the occurrence and development of atherosclerosis combined with MR.

关 键 词：动脉粥样硬化 抗体 磁共振成像 分子影像 

分 类 号：R543.5[医药卫生—心血管疾病]