自制纳米级E-选择素靶向超声微泡对缺血心肌分子成像

Ultrasounic molecular imaging for myocardial ischemic using E-selectin targeting nanometer microbubbles

目的采用自制的携E-选择素抗体的纳米级靶向超声造影剂对大鼠缺血再灌注损伤后的缺血心肌进行超声分子成像,评估其检测缺血心肌的可行性。方法采用生物素-链亲和素方法制备纳米级靶向微泡,应用荧光显微镜及流式细胞仪检测微泡形态及抗体连接效率;将26只SD大鼠随机分为E-选择素靶向微泡组(MBE组,n=10)、IGg抗体微泡组(MBIGg组,n=10)、普通微泡组(MBC组,n=6),制备心肌缺血再灌注损伤模型,将冠状动脉左前降支阻断15min后恢复灌注,于再灌注后6h经尾静脉分别注射3种微泡行CEUS。后行病理学检查。结果 MBE组缺血区域声学强度(VI)显著高于非缺血区(P<0.05),也显著高于MBC组、MBIGg组缺血区域的VI(P<0.05);MBC组、MBIGg组缺血区域与非缺血区的VI差异无统计学意义(P>0.05)。结论纳米级E-选择素靶向超声微泡可以早期检测到缺血心肌,有望实现缺血心肌的"记忆"成像。

Objective To develop an echocardiographic molecular imaging approach for detecting recent myocardial ischemia using self-made E-selectin targeting nanometer microbubbles,and assess the recent cardiac ischemia.Methods Lipid nanometer microbubbles bearing recombinant E-selectin（MBE）or nonspecific IGg（MBIGg）were prepared using avidin-biotin bridge,then observed and evaluated by fluorescence microscope and flow cytometry.Twenty-six rats were randomly divided into MBE,MBIGg,and MBC group.Ischemia-reperfusion injury of myocardium was performed with left anterior descending（LAD）occluded for 15 min and then reperfused,and CEUS with MBE,MBIGg,and MBCwas performed 6hafter reperfusion respectively.Postmortem the heart was excised for pathological observation.Results Ultrasound imaging after injection of MBEdemonstrated persistent contrast enhancement of the previously ischemic regions.Videointensity（VI）in the postischemic myocardium after injection of MBE was higher than that in nonischemic regions（P〈0.05）,and higher than that after MBIGgor MBCinjection（all P〈0.05）.VI in the postischemic regions after MBIGgor MBCinjection was not significantly different from the nonischemic regions（P〉0.05）.Conclusion Echocardiographic molecular imaging with nanometer microbubbles bearing E-selectin antibodies could detect recent ischemia,setting the stage for myocardial ischemic memory imaging.