靶向动脉粥样硬化斑块内腱糖蛋白-C表达磁共振体内成像的实验研究  

Feasibility of targeted magnetic resonance imaging on visualizing tenascin-C expression in atherosclerosis plaque in high-fat diet fed ApoE^-/-mice

作　　者：孟欢[1] 马占龙[2] 严海浪[3] 陈相汛[2] 尚松安[4] 余静[2] 宋佳成 施海彬[2] 

机构地区：[1]南京医科大学附属南京儿童医院放射科,210029 [2]南京医科大学第一附属医院放射科 [3]南京医科大学附属江苏盛泽医院放射科 [4]苏北人民医院放射科

出　　处：《中华心血管病杂志》2016年第4期342-347,共6页Chinese Journal of Cardiology

摘　　要：目的 观察腱糖蛋白-C（TN-C）在动脉粥样硬化斑块中的表达变化,并探讨磁共振靶向TN-C体内成像的可行性.方法 雄性载脂蛋白E基因敲除（ApoE-/-）小鼠,10周龄,采用高脂饮食法建立主动脉粥样硬化模型,其中靶向探针组8只,对照组6只.高脂饲养14周后,使用7.0T小动物MR成像仪（7.0T micro-MRI）观察主动脉斑块情况;采用苏木素伊红染色、油红O染色观察主动脉血管壁病理学改变,免疫组织化学检测TN-C在主动脉粥样硬化斑块内的表达情况;化学耦联法合成抗体靶向TN-C的磁共振成像探针（抗TN-C-USPIO探针）,并通过尾静脉注入靶向探针组小鼠体内,对照组注射单纯超小超顺磁性氧化铁颗粒（USPIO）,并于注射8h后行磁共振扫描,观察两组小鼠腹主动脉内膜信号变化.成像后立即取两组小鼠腹主动脉作为标本,行普鲁士蓝染色,观察斑块内铁颗粒的沉积.结果 开始建模14周后,磁共振成像可见小鼠腹主动脉壁增厚,T1WI、PDWI为稍高信号,T2WI为稍低信号,苏木素伊红染色可见动脉内膜明显增厚,油红O染色证实为脂质沉积,免疫组织化学示TN-C在动脉粥样硬化斑块内高表达.靶向探针组小鼠注射抗TN-C-USPIO探针8h后,可见增厚的血管壁T2WI信号较注射前明显降低（△OD值=4.78±1.41,=9.59,P＜0.05）,而对照组注射单纯USPIO前后则无明显变化（△OD值=1.45±1.01,t=1.93,P＞0.05）;普鲁士蓝染色结果示靶向探针组小鼠腹主动脉内粥样硬化斑块内可见蓝染颗粒（铁颗粒沉积）,而对照组则蓝染极少.结论 TN-C在动脉粥样硬化斑块内高表达,而磁共振靶向TN-C体内成像可显示这一变化,为进一步开展斑块内磁共振分子影像学研究提供了依据.Objective To explore the feasibility of targeted magnetic resonance imaging （MRI）on visualizing tenascin-C （TN-C） expression in atherosclerotic plaque in high-fat diet fed ApoE-/-mice.Methods Aorta artery atherosclerosis was induced in high fat diet fed ApoE-/-mice.The atherosclerotic plaques were observed by 7.0T micro-MRI after 14 weeks.Specimens of the samples were obtained randomly and stained with HE and oil red O to observe the pathological changes.The plaques were stained with anti-TN-C antibody to detecting the TN-C.Targeted probe （anti-TN-C-USPIO） was synthesized through chemical coupling methods.The experimental group was injected with targeted probe through tail vein （10 mgFe/kg）,and USPIO was used as controls.MRI was performed 8 hours thereafter,intima signal changing in abdominal aorta was observed;specimens of abdominal aorta were taken after scanning,and were stained by Perl＆#39;s Prussian blue,the deposition of iron particles was observed.Results Compared with baseline level,MRI evidenced thickened aorta wall;signal was enhanced on T1WI and PDWI,but weakened on T2WI after 14 weeks.HE stained tissue samples demonstrated thicker intima.The plaque was confirmed by the oil red O staining.Immunohistochemistry staining showed significantly upregulated TN-C expression in the plaque.Compared to pre-injection status,MRI signal was lost on T2WI in the atherosclerotic lesions at 8 hours after anti-TNC-USPIO injection （△OD =4.78 ± 1.41,t =9.59,P 〈 0.05）,while T2WI remained unchanged in control group （△OD =1.45 ± 1.01,t =1.93,P 〉 0.05） and matched Perl＆#39; s Prussian stained section showed enriched blue particles deposition within the plaque while there were only scarce blue particles deposition in the control group.Conclusion Our results show that targeted MRI is feasible to detect TN-C expression in the plaque in vivo,this method might be used to detect in vivo atherosclerotic plaque in large animals or in humans in the future.

关 键 词：动脉粥样硬化 磁共振成像 腱糖蛋白 

分 类 号：R543.5[医药卫生—心血管疾病]