用二甲基二硫代氨基甲酸钠-超顺磁性氧化铁纳米颗粒在阿尔茨海默病大鼠模型中检测β-淀粉样蛋白斑块

The detection of β-amyloid plaques in an Alzheimer's disease rat model with DDNP-SPIO.

作者信息

Zhang D, Fa H-B, Zhou J-T, Li S, Diao X-W, Yin W

机构信息

Department of Radiology, XinQiao Hosptial, Third Military Medical University, ChongQing 400037, People's Republic of China.

College of Chemistry and Chemical Engineering, ChongQing University, Chongqing 400044, People's Republic of China.

出版信息

Clin Radiol. 2015 Jan;70(1):74-80. doi: 10.1016/j.crad.2014.09.019. Epub 2014 Nov 15.

Abstract

AIM

To detect the β-amyloid plaques (Aβ) in a rat model of Alzheimer's disease (AD) using superparamagnetic iron oxide nanoparticles coated with 1,1-dicyano-2-[6-(dimethylamino)-naphthalene-2-yl] propene carboxyl derivative (DDNP-SPIO).

MATERIALS AND METHODS

DDNP-SPIO was prepared in a previous trial. The binding affinity of DDNP-SPIO to Aβ was tested using fluorescence spectrophotometry in vitro. In vivo, five AD rats and five non-AD rats were intravenously injected with DDNP-SPIO at a dose of 76 μmol Fe/kg. Coronal T2*-weighted images were collected at baseline and repeated at 10, 30, and 60 min post-injection. Enhancement features of the two groups were analysed. After imaging, brain specimens were resected for Congo red and Prussian blue staining to assess the binding of DDNP-SPIO to Aβ deposits.

RESULTS

In vitro experiments indicated that the DDNP-SPIO nanoparticles displayed high binding affinities towards Aβ with a Kd value of 29.4 nmol/l. A significant decrease in SI was detected in the hippocampal area of AD rats after intravenous injection of the nanoparticles, but not in non-AD rats. The measurement of the percentage signal loss decreased to 52% in AD rats. In non-AD rats, only 10% signal loss was observed. There was a significant difference between the two groups (t = 4.533, p < 0.05). The signal decrease resulted from the binding of the DDNP-SPIO nanoparticles to the Aβ plaques, which was identified with Congo red and Prussian blue staining.

CONCLUSION

The DDNP-SPIO nanoparticles could potentially be used for visualizing Aβ plaques, which may be helpful for diagnosing the early stages of AD and monitoring the effects of drug therapy.

摘要

目的

使用涂有1,1 - 二氰基 - 2 - [6 - (二甲基氨基) - 萘 - 2 - 基]丙烯羧基衍生物(DDNP - SPIO)的超顺磁性氧化铁纳米颗粒,检测阿尔茨海默病(AD)大鼠模型中的β - 淀粉样蛋白斑块(Aβ)。

材料与方法

DDNP - SPIO在先前的试验中制备。使用荧光分光光度法在体外测试DDNP - SPIO与Aβ的结合亲和力。在体内,五只AD大鼠和五只非AD大鼠以76 μmol Fe/kg的剂量静脉注射DDNP - SPIO。在基线时采集冠状位T2 *加权图像,并在注射后10、30和60分钟重复采集。分析两组的增强特征。成像后,切除脑标本进行刚果红和普鲁士蓝染色,以评估DDNP - SPIO与Aβ沉积物的结合情况。

结果

体外实验表明,DDNP - SPIO纳米颗粒对Aβ表现出高结合亲和力,Kd值为29.4 nmol/l。静脉注射纳米颗粒后,AD大鼠海马区的信号强度(SI)显著降低,而非AD大鼠未出现这种情况。AD大鼠的信号损失百分比测量值降至52%。在非AD大鼠中,仅观察到10%的信号损失。两组之间存在显著差异(t = 4.533,p < 0.05)。信号降低是由于DDNP - SPIO纳米颗粒与Aβ斑块结合所致,通过刚果红和普鲁士蓝染色得以证实。

结论

DDNP - SPIO纳米颗粒可能可用于可视化Aβ斑块,这可能有助于诊断AD的早期阶段并监测药物治疗效果。

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