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[靶向磁共振成像对高脂饮食喂养的ApoE(-/-)小鼠动脉粥样硬化斑块中肌腱蛋白-C表达的可视化可行性]

[Feasibility of targeted magnetic resonance imaging on visualizing tenascin-C expression in atherosclerosis plaque in high-fat diet fed ApoE(-/-) mice].

作者信息

Meng H, Ma Z L, Yan H L, Chen X X, Shang S A, Yu J, Song J C, Shi H B

机构信息

Department of Radiology, Nanjing Children's Hospital Affilicated with Nanjing Medical University, Nanjing 210029, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2016 Apr 24;44(4):342-7. doi: 10.3760/cma.j.issn.0253-3758.2016.04.013.

Abstract

OBJECTIVE

To explore the feasibility of targeted magnetic resonance imaging (MRI)on visualizing tenascin-C (TN-C) expression in atherosclerotic plaque in high-fat diet fed ApoE(-/-) mice.

METHODS

Aorta artery atherosclerosis was induced in high fat diet fed ApoE(-/-) mice. The atherosclerotic plaques were observed by 7.0T micro-MRI after 14 weeks. Specimens of the samples were obtained randomly and stained with HE and oil red O to observe the pathological changes. The plaques were stained with anti-TN-C antibody to detecting the TN-C. Targeted probe (anti-TN-C-USPIO) was synthesized through chemical coupling methods. The experimental group was injected with targeted probe through tail vein (10 mgFe/kg), and USPIO was used as controls. MRI was performed 8 hours thereafter, intima signal changing in abdominal aorta was observed; specimens of abdominal aorta were taken after scanning, and were stained by Perl's Prussian blue, the deposition of iron particles was observed.

RESULTS

Compared with baseline level, MRI evidenced thickened aorta wall; signal was enhanced on T1WI and PDWI, but weakened on T2WI after 14 weeks. HE stained tissue samples demonstrated thicker intima. The plaque was confirmed by the oil red O staining. Immunohistochemistry staining showed significantly upregulated TN-C expression in the plaque. Compared to pre-injection status, MRI signal was lost on T2WI in the atherosclerotic lesions at 8 hours after anti-TNC-USPIO injection (ΔOD =4.78±1.41, t=9.59, P<0.05), while T2WI remained unchanged in control group (ΔOD =1.45±1.01, t=1.93, P>0.05) and matched Perl's Prussian stained section showed enriched blue particles deposition within the plaque while there were only scarce blue particles deposition in the control group.

CONCLUSION

Our results show that targeted MRI is feasible to detect TN-C expression in the plaque in vivo, this method might be used to detect in vivo atherosclerotic plaque in large animals or in humans in the future.

摘要

目的

探讨靶向磁共振成像(MRI)在可视化高脂饮食喂养的ApoE(-/-)小鼠动脉粥样硬化斑块中肌腱蛋白-C(TN-C)表达的可行性。

方法

对高脂饮食喂养的ApoE(-/-)小鼠诱导主动脉动脉粥样硬化。14周后用7.0T微型MRI观察动脉粥样硬化斑块。随机获取样本标本,进行HE染色和油红O染色以观察病理变化。用抗TN-C抗体对斑块进行染色以检测TN-C。通过化学偶联方法合成靶向探针(抗TN-C-USPIO)。实验组经尾静脉注射靶向探针(10mgFe/kg),以超顺磁性氧化铁(USPIO)作为对照。此后8小时进行MRI检查,观察腹主动脉内膜信号变化;扫描后取腹主动脉标本,进行普鲁士蓝染色,观察铁颗粒沉积情况。

结果

与基线水平相比,MRI显示主动脉壁增厚;14周后T1WI和质子密度加权成像(PDWI)信号增强,T2WI信号减弱。HE染色的组织样本显示内膜增厚。油红O染色证实有斑块。免疫组织化学染色显示斑块中TN-C表达明显上调。与注射前状态相比,注射抗TNC-USPIO后8小时,动脉粥样硬化病变处T2WI上的MRI信号消失(ΔOD =4.78±1.41,t=9.59,P<0.05),而对照组T2WI保持不变(ΔOD =1.45±1.01,t=1.93,P>0.05),匹配的普鲁士蓝染色切片显示斑块内有丰富的蓝色颗粒沉积,而对照组仅有少量蓝色颗粒沉积。

结论

我们的结果表明,靶向MRI在体内检测斑块中TN-C表达是可行的,该方法未来可能用于检测大型动物或人类体内的动脉粥样硬化斑块。

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