白细胞介素18靶向超声微泡对动脉斑块分子成像的实验研究

目的研究白细胞介素18（IL-18）靶向超声微泡对动脉粥样硬化斑块的超声分子成像。 方法以高脂喂养-免疫损伤法构建实验兔动脉粥样硬化斑块模型，超声检查监测动脉造模过程。以生物素-亲和素法制备IL-18靶向超声微泡，实验动物麻醉后随机使用裸微泡（MBc）及靶向微泡（MBt）分别对动脉斑块进行超声造影检查，检查结束后处死动物取目标斑块行病理检查及Western-blotting检测。 结果10只实验兔成功构建动脉粥样硬化模型，光学显微镜观察MBt物理性质稳定，荧光显微镜显示MBt表面带有均匀的绿色光环。对目标斑块超声造影强度行半定量分析，MBc组平均强度为202 ± 18，MBt组平均强度为237 ± 7，差异有统计学意义（t=6.472，P < 0.001）。病理检查示动脉管腔内见粥样斑块形成，Western-blotting检测示斑块内均可检测到IL-18蛋白表达，相关性分析示MBc组造影强度与斑块内IL-18蛋白表达相对量没有相关性（r=0.534，P=0.112），MBt组造影强度与斑块内IL-18蛋白表达相对量呈线性正相关（r=0.904，P < 0.001）。 结论MBt对粥样斑块的显影能力优于MBc，可实现动脉粥样硬化斑块早期、敏感、特异性的诊断和治疗。

Experimental study on molecular imaging of atherosclerotic plaques by targeted interleukin-18 ultrasonic microbubbles

ObjectiveTo investigate whether targeted interleukin-18 (IL-18) ultrasonic microbubbles can improve molecular imaging of atherosclerotic plaques. MethodsAn atherosclerotic plaque rabbit model was established using a high-fat diet and immunologic injury method. The locations of atherosclerotic plaques were verified by ultrasonography. Targeted IL-18 ultrasonic microbubbles were prepared by the biotin-avidin method. After being anesthetized, the experimental rabbits were randomized to use control microbubbles (MBc) and targeted microbubbles (MBt) to perform contrast-enhanced ultrasound examination of atherosclerotic plaques. After rabbits were sacrificed, the targeted plaques were taken for pathological examination and Western-blotting analysis. ResultsThe atherosclerosis model was successfully constructed in 10 experimental rabbits. Light microscope showed stable physical properties of MBt and fluorescence microscopy showed uniform green halos on the surface of MBt. Semiquantitative analysis of contrast-enhanced intensity of targeted plaques revealed that the average intensity of MBc group was 202 ± 18, and that of MBt group was 237 ± 7. The difference was statistically significant (t=6.472, P < 0.001). Pathological examination indicated atheromatous plaques in the lumen of arteries; Western-blotting analysis indicated IL-18 expressions in the plaques. Correlation analysis showed contrast-enhanced intensity of MBc group and IL-18 expression in the plaques had no correlation (r=0.534, P=0.112), while that of MBt group and IL-18 expression had linear positive correlation (r=0.904, P < 0.001). ConclusionMBt can better facilitate the detection of atherosclerotic plaques than MBc and be used for early, sensitive and specific diagnosis and treatment of atherosclerotic plaques.