目的:探讨携抗细胞间黏附分子-1(ICAM-1)靶向微泡对兔心肌梗死后受损内皮的靶向识别能力。方法:分别制备携抗ICAM-1的阳离子靶向微泡及携抗ICAM-1的Sono Vue靶向微泡,以不带ICAM-1的单纯阳离子微泡和Sono Vue微泡作为对照;显微镜下观察4种微泡与白细胞介素-1β刺激后的人脐静脉内皮细胞HUVEC的结合情况;用FITC荧光分别标记各组微泡;制备兔心肌梗死模型,于造模后3d经耳缘静脉分别注射各组微泡,经胸超声检测4组兔心肌造影情况,之后处死兔获取心脏标本,冰冻切片检测靶组织中荧光情况。结果:显微镜检测显示HUVEC周围可见较多携抗ICAM-1阳离子或Sono Vue微泡聚集黏附,而单纯阳离子微泡和单纯Sono Vue微泡无明显黏附现象;兔心肌造影显示抗ICAM-1阳离子靶向微泡组和携抗ICAM-1的Sono Vue微泡组显影持续时间高于单纯阳离子微泡组和Sono Vue微泡组;冰冻切片荧光显微镜结果显示携抗ICAM-1阳离子微泡组和携抗ICAM-1的Sono Vue微泡组梗死区中受损血管内膜面可见明亮的绿色荧光,而单纯阳离子组和Sono Vue微泡组血管内膜面仅见少量暗淡的绿色荧光。结论:携抗ICAM-1的靶向微泡可特异识别受损的血管内皮,有助于目的基因的靶向释放。
Objective: To investigate the ability that cationic microbubbles carrying intercellular adhe- sion molecule (ICAM)-I antibody targeted recognition of injured endothelium in rabbits after my- ocardial infarction. Methods:Cationic and SonoVue microbubbles carrying ICAM-1 antibody were prepared and the combination between microbubbles and HUVECs stimulated with interleukin-1β was observed under the microscope. The cationic and SonoVue microbubbles without carrying ICAM-1 antibody were served as the control group. Rabbit myocardial infarction models were constructed. The microbubbles in each group were injected through ear marginal vein 3 days after myocardial infarction. The contrast myocardial echocardiography was performed and then the rabbits were sacrificed and the specimens of heart were obtained. The fluorescence in target tissue was detected by frozen sections. Results: Numerous cationic and SonoVue microbubbles carrying ICAM-1 antihody were adhered around HUVEC, and few cationic or SonoVue mierobubbles without carrying ICAM-1 antibody were adhered around HUVEC. The contrast myocardial echo- cardiography showed that the duration time of cationic microbubbles and SonoVue microbubbles carrying ICAM-1 antibody were longer than that of the control group. Fluorescent frozen sections showed that the significant green fluorescence was observed in endothelium of injured arteries of myocardial infarction area in cationic and SonoVue microbubbles carrying ICAM-1 antibody group, and only few dim green fluorescence was observed in the arterial endothelium in the con- trol group. Conclusion. The microbubbles carrying ICAM-1 antibody could recognize injured en- dothelium and improve the ability of microbubbles carrying gene release qualitatively.