| 纳米银颗粒通过血脑屏障中剂量-效应关系的初步研究 |
| A Preliminary Study on the Dose-Effect Relation when Silver Nanoparticles Crossing through the Blood-Brain Barrier in vitro |
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| 摘要: 目的:本文研究了纳米银颗粒通过血脑屏障的剂量-效应关系,并对其通过血脑屏障的机理进行了初步推测。方法:研究中先建立了一个体外血脑屏障模型,再以纳米银颗粒为试验样品、微米银颗粒为对照样品,将不同浓度(25～400 μg·mL-1)的试样和对照样加入体外血脑屏障模型中共同培养4 h,之后利用ICP-MS测定通过血脑屏障的银颗粒百分比,并采用TEM观察BBB细胞的超微结构。结果:在相同剂量下,只有纳米银颗粒能通过血脑屏障;当纳米银颗粒的剂量小于100 μg·mL-1时,血脑屏障结构完整,有约2%纳米银颗粒通过血脑屏障;当纳米银颗粒剂量在100～400 μg·mL-1的范围内时,随纳米银颗粒剂量增加,纳米银颗粒通过血脑屏障的比率也会相应增加,而且血脑屏障结构被破坏的程度也相应增加。纳米银颗粒剂量为400 μg·mL-1时,有约15%的纳米银颗粒通过了血脑屏障。结论:初步推断,在剂量较低时,纳米银颗粒主要通过“细胞转运机理”通过血脑屏障,当剂量大到足以对脑毛细血管内皮细胞产生足够的细胞毒性时,“细胞毒性机理”将起主要作用。这也提示我们,即使剂量很小,纳米银颗粒仍能通过血脑屏障。因此在使用含有纳米银颗粒的医用产品甚至保健品时应持谨慎的态度。 |
| 关键词: 纳米银颗粒 血脑屏障 剂量-关系效应 |
| 基金项目: 北京市自然科学基金(No.3112024),中国食品药品检定研究院中青年发展研究基金(No.2009C4)资助项目。 |
| Abstract: Objective:The aim of this study was to investigate the dose-effect relation of the ability that silver nanoparticles (SNPs) crossing through the blood-brain barrier (BBB) and presume its mechanism. Methods:In this study, SNPs were test samples and silver microparticles (SMPs) acted as control samples. First, an in vitro BBB model was established. Second, SNPs or SMPs were cultured in the BBB model at different dose from 25 μg·mL-1 to 400 μg·mL-1, respectively. After 4 hours of culture, the ultrastructure of BBB and the percentage of silver particles crossing through BBB were evaluated with TEM and ICP-MS respectively. Results:Results demonstrated that SNPs crossed the BBB, while the SMPs did not. When SNPS dose<100 μg·mL-1, about 2% silver particles crossed BBB, and the BBBs ultrastructures were normal. When dose>100 μg·mL-1, the higher dose is, the more silver particles crossed BBB, and the more damage occurred in the BBBs ultrastructures. When dose=400 μg·mL-1, about 15% silver particles crossed BBB. Conclusion:The results suggested that membrane-mobile transport mechanism is the main way allowing SNPs to cross the BBB in low dose. Cytotoxicity mechanism is the main way allowing SNPs to cross the BBB in higher dose. It is also suggested that SNPs could cross the BBB even in a low dose. A cautious attitude would be hold before silver nanoparticles-based medical devices were used in clinical practice. |
| Keywords: silver nanoparticle blood-brain barrier dose-effect relation |
| 投稿时间：2012-12-25 修订日期：2013-01-21 |
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| 汤京龙,王硕,刘丽,王春仁,奚廷斐.纳米银颗粒通过血脑屏障中剂量-效应关系的初步研究[J].无机化学学报,2013,29(5):1025-1030. |
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