近红外荧光分子标记的LOX-1抗体靶向小鼠动脉粥样硬化模型的成像研究-东南大学学报医学版

近红外荧光分子标记的LOX-1抗体靶向小鼠动脉粥样硬化模型的成像研究

单位：东南大学医学院, 江苏省分子影像与功能影像重点实验室, 江苏南京 210009

分类号：R-332;R543.1;R445.9

出版年·卷·期（页码）：2012·31·第六期（665-670）

摘要：

目的:探讨近红外荧光分子标记的凝集素样氧化低密度脂蛋白受体-1(LOX-1)抗体探针在ApoE-/-鼠主脉动脉粥样硬化近红外荧光(NIRF)成像中的可行性。方法:将ApoE-/-小鼠以高脂饮食喂养20周,建立动脉粥样硬化模型。将24只ApoE-/-动脉粥样硬化模型小鼠随机分为3组,即抗LOX-1抗体-NIR-797组、非特异性IgG-NIR-797组和单纯磷酸盐缓冲液(PBS)组,每组8只,分别经尾静脉注入抗LOX-1抗体-NIR-797、非特异性IgG-NIR-797和单纯PBS。另取8只C57BL/6小鼠作为对照组,经尾静脉注入抗LOX-1抗体-NIR-797,注入探针24h后取小鼠主动脉及主要脏器行NIRF成像,再取主动脉行油红O染色,比较NIRF成像面积和油红O染色面积比例的差异。结果:ApoE-/-小鼠经尾静脉注入抗LOX-1抗体-NIR-797探针24h后,NIRF成像显示有强荧光信号聚集于小鼠离体主动脉的斑块区域,而注入非特异性IgG-NIR-797组斑块区信号明显减弱,PBS组及对照组C57BL/6小鼠仅见较弱荧光信号,单因素方差分析结果显示差异有统计学意义(F=232,P<0.001)。NIRF阳性面积与斑块油红O染色面积比例分别为(42.70±1.25)%和(42.78±1.51)%,两者差异无统计学意义(t=0.409,P=0.695)。结论:近红外荧光分子标记的抗LOX-1抗体探针能够特异性地显示ApoE-/-鼠主动脉粥样硬化斑块的分布,可以作为小鼠动脉粥样硬化斑块成像的有效工具,LOX-1将来可能成为一个新的评价动脉粥样硬化的良好靶点。

Objective: To explore the role of near-infrared fluorescence (NIRF) probes NIR-797 targeted anti-LOX-1 antibodies in atherosclerotic lesions imaging in aortic atherosclerosis lesions of ApoE deficient mice. Methods: Apolipoprotein E -/- (ApoE -/-) mice were fed with high cholesterol diet for 20 weeks to establish atherosclerotic model. Twenty-four ApoE -/- mice were randomly divided into 3 groups(8 in each group) and injected with anti-LOX-1-Ab-NIR-797, IgG-NIR-797 and phosphate buffered saline (PBS) respectively. Eight wild-type C57BL/6 mice were injected with anti-LOX-1-Ab-NIR-797 as control group. NIRF imaging of the aortas and major organs were performed 24 hours after tail vein injection of probes, followed by aortic excision for oil red O staining. Reults: NIRF imaging showed significant fluorochrome enhancement accumulation in atherosclerotic plaques in ApoE -/-mice with the anti-LOX-1-Ab-NIR-797 probe but not enough with the nonspecific IgG probe. Little signal enhancement was observed in ApoE-/- mice injected with the PBS and Wild-type C57BL/6 mice injected with anti-LOX-1-Ab-NIR-797 probe. The percentage of positive areas in imaging of NIRF and oil red O staining 24 h after injection of NIR-797 labeled anti-LOX-1 antibody were (42.70±1.25)% and (42.78±1.51)%. The difference between them was not statistically significant (t=0.409,P=0.695). Conclusion: This study demonstrates that anti-LOX-1-Ab-NIR-797 can be used in imaging atherosclerotic lesions. LOX-1 may be used as a target for molecular imaging of atherosclerotic plaque.

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