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中华危重症医学杂志(电子版)

中华危重症医学杂志(电子版) ›› 2018, Vol. 11 ›› Issue (02) : 100 -103. doi: 10.3877/cma.j.issn.1674-6880.2018.02.006

所属专题： 文献；

论著

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
江珍珍1, 刘夏天1, 马彩叶1, 侯传玲2, 程祖胜3, 夏国园3,†()   
  1. 1. 312000　浙江绍兴，绍兴市人民医院超声科
    2. 312000　浙江绍兴，绍兴市人民医院病理科
    3. 312000　浙江绍兴，绍兴文理学院附属医院超声科
  • 收稿日期:2017-08-15 出版日期:2018-04-01
  • 通信作者: 夏国园
  • 基金资助:
    浙江省医药卫生一般研究计划项目(2015KYA220、2015KYA225); 绍兴市公益性技术应用研究计划项目(2014B70053)

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

Zhenzhen Jiang1, Xiatian Liu1, Caiye Ma1, Chuanlin Hou2, Zusheng Cheng3, Guoyuan Xia3,†()   

  1. 1. Department of Ultrasound, Shaoxing People's Hospital, Shaoxing 312000, China
    2. Department of Pathology, Shaoxing People's Hospital, Shaoxing 312000, China
    3. Department of Ultrasound, Affiliated Hospital of Shaoxing University, Shaoxing 312000, China
  • Received:2017-08-15 Published:2018-04-01
  • Corresponding author: Guoyuan Xia
  • About author:
    Corresponding author: Xia Guoyuan, Email:
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引用本文：

江珍珍, 刘夏天, 马彩叶, 侯传玲, 程祖胜, 夏国园. 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[J]. 中华危重症医学杂志(电子版), 2018, 11(02): 100-103.

Zhenzhen Jiang, Xiatian Liu, Caiye Ma, Chuanlin Hou, Zusheng Cheng, Guoyuan Xia. Experimental study on molecular imaging of atherosclerotic plaques by targeted interleukin-18 ultrasonic microbubbles[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2018, 11(02): 100-103.

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。

关键词: 白细胞介素18, 超声, 靶向微泡, 动脉斑块, 分子成像
Objective

To investigate whether targeted interleukin-18 (IL-18) ultrasonic microbubbles can improve molecular imaging of atherosclerotic plaques.

Methods

An 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.

Results

The 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).

Conclusion

MBt can better facilitate the detection of atherosclerotic plaques than MBc and be used for early, sensitive and specific diagnosis and treatment of atherosclerotic plaques.

Key words: Interleukin-18, Ultrasound, Targeted microbubble, Atherosclerotic plaques, Molecular imaging
[1]
Spencer FA, Emery C, Lessard D, et al. The Worces-ter Venous Thromboembolism study: a population-based study of the clinical epidemiology of venous thromboembolism[J]. J Gen Intern Med, 2006, 21 (7): 722-727.
[2]
Campbell IC, Suever JD, Timmins LH, et al. Biomech-anics and inflammation in atherosclerotic plaque erosion and plaque rupture: implications for cardiovascular events in women[J]. PLoS One, 2014, 9 (11): e111785.
[3]
Chen MC, Chen CJ, Yang CH, et al. Interleukin-18: a strong predictor of the extent of coronary artery disease in patients with unstable angina[J]. Heart Vessels, 2007, 22 (6): 371-375.
[4]
江珍珍，刘夏天，夏国园，等.超声实时组织弹性成像检测兔腹主动脉粥样硬化斑块[J].中国医学影像技术，2016，32（11）：1635-1638.
[5]
Zhang C, Huang P, Zhang Y, et al. Anti-tumor effic-acy of ultrasonic cavitation is potentiated by concurrent delivery of anti-angiogenic drug in colon cancer[J]. Cancer Lett, 2014, 347 (1): 105-113.
[6]
Wei S, Fu N, Sun Y, et al. Targeted contrast-enhanced ultrasound imaging of angiogenesis in an orthotopic mouse tumor model of renal carcinoma[J]. Ultrasound Med Biol, 2014, 40 (6): 1250-1259.
[7]
Wong KS, Caplan LR, Kim JS. Stroke mechanisms[J]. Front Neurol Neurosci, 2016 (40): 58-71.
[8]
中华医学会心血管病分会介入心脏病学组，中华心血管病杂志编辑委员会.中国经皮冠状动脉介入治疗指南2012（简本）[J].中华心血管病杂志，2012，40（4）:271-277.
[9]
彤丹，闫玮. 2型糖尿病患者颈动脉内-中膜厚度与血管内皮功能的超声评价及其相关性研究[J/CD].中华危重症医学杂志（电子版），2014，7（2）：123-125.
[10]
Skagen K, Skjelland M, Zamani M, et al. Unstable ca-rotid artery plaque: new insights and controversies in diagnostics and treatment[J]. Croat Med J, 2016, 57 (4): 311-320.
[11]
Mani S, Untereiner A, Wu L, et al. Hydrogen sulfide and the pathogenesis of atherosclerosis[J]. Antioxid Redox Signal, 2014, 20 (5): 805-817.
[12]
Okamura H, Tsutsi H, Komatsu T, et al. Cloning of a new cytokine that induces IFN-gamma production by T cells[J]. Nature, 1995, 378 (6552): 88-91.
[13]
Ragino YI, Chernyavski AM, Polonskaya YV, et al. Activity of the inflammatory process in different types of unstable atherosclerotic plaques[J]. Bull Exp Biol Med, 2012, 153 (2): 186-189.
[14]
Hong K, Oh K, Lee S, et al. Recombinant Fc-IL-18BPc isoform inhibits IL-18-induced cytokine production[J]. Hybridoma (Larchmt), 2012, 31 (2): 99-104.
[15]
Pigarevskii PV, Maltseva SV, Snegova VA, et al. Role of interleukin-18 in destabilization of the atherosclerotic plaque in humans[J]. Bull Exp Biol Med, 2014, 157 (6): 821-824.
[16]
Yuen CM, Chiu CA, Chang LT, et al. Level and valu-e of interleukin-18 after acute ischemic stroke[J]. Circ J, 2007, 71 (11): 1691-1696.
[17]
韦馨，唐红.靶向超声造影剂在制备领域中的研究进展[J].临床超声医学杂志，2012，14（12）：833-836.
[18]
Zhang YJ, Bai DN, Du JX, et al. Ultrasound-guided imaging of junctional adhesion molecule-A-targeted microbubbles identifies vulnerable plaque in rabbits[J]. Biomaterials, 2016 (94): 20-30.
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