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纳米银颗粒对动物大脑的神经毒性:系统评价和荟萃分析。

Neurotoxicity of silver nanoparticles in the animal brain: a systematic review and meta-analysis.

机构信息

Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran.

Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Forensic Toxicol. 2022 Jan;40(1):49-63. doi: 10.1007/s11419-021-00589-4. Epub 2021 Jul 29.

DOI:10.1007/s11419-021-00589-4
PMID:36454484
Abstract

OBJECTIVE

About 30% of all nanoparticle products contain silver nanoparticles (AgNPs). With the increasing use of AgNPs in industry and medicine, concerns about the adverse effects on the environment, and the possible toxicity of these particles to primary cells and towards organs such as the brain and nervous system increased. In this paper, the toxicity of AgNPs in neurons and brain of animal models was investigated by a systematic review and meta-analysis.

METHODS

The full texts of 26 relevant studies were reviewed and analyzed. Data from nine separate experiments in five articles were analyzed by calculating the standardized mean differences between viability of treated animals and untreated groups. Subgroup analysis was conducted. In addition, a systematic review provided a complete, exhaustive summary of all articles.

RESULTS

The results of the meta-analysis showed that AgNPs are able to cause neuronal death after entering the brain (standardized mean difference (SMD) = 2.87; 95% confidence interval (CI) 2.1-3.61; p < 0.001). AgNPs sized smaller or larger than 10 nm could both cause neuronal cell death. This effect could be observed for a long time (up to 6 months). Neurons from embryonic animals whose mothers had been exposed to AgNPs during pregnancy were affected as much as animals that were themselves exposed to AgNPs. Toxic effects of AgNPs on memory and cognitive function were also observed. Studies have shown that inflammation and increased oxidative stress followed by apoptosis are likely to be the main mechanisms of AgNPs toxicity.

CONCLUSION

AgNPs can enter the brain with a long half-life and it can cause neuronal death after entering the brain. AgNPs can manifest proinflammatory cascades in the CNS and BBB. Some toxic effects were detected in the cerebral cortex, hypothalamus, hippocampus and others. Studies have shown that inflammation and increased oxidative stress lead to apoptosis, the main mechanism of AgNPs neurotoxicity, which can be caused by an increase in silver ions from AgNPs.

摘要

目的

约 30%的纳米颗粒产品都含有银纳米颗粒(AgNPs)。随着 AgNPs 在工业和医学领域的应用日益广泛,人们对其可能对环境造成的不良影响以及对包括大脑和神经系统在内的器官的潜在毒性的担忧也与日俱增。本研究通过系统综述和荟萃分析,调查了 AgNPs 在动物模型神经元和大脑中的毒性。

方法

共查阅了 26 篇相关研究的全文,并进行了分析。将五篇文章中的 9 个独立实验的数据进行了计算,得出处理组动物与未处理组动物存活率之间的标准化均数差。并进行了亚组分析。此外,系统综述提供了对所有文章的完整详尽的总结。

结果

荟萃分析结果表明,AgNPs 进入大脑后能够引起神经元死亡(标准化均数差(SMD)=2.87;95%置信区间(CI)2.1-3.61;p<0.001)。粒径小于或大于 10nm 的 AgNPs 均可导致神经元细胞死亡。这种影响可持续很长时间(长达 6 个月)。在怀孕期间暴露于 AgNPs 的母体的胚胎动物的神经元,以及自身暴露于 AgNPs 的动物的神经元,都受到了影响。AgNPs 对记忆和认知功能的毒性作用也被观察到。研究表明,AgNPs 毒性的主要机制可能是炎症和氧化应激增加导致的细胞凋亡。

结论

AgNPs 可以进入大脑,且半衰期长,进入大脑后可引起神经元死亡。AgNPs 可以在中枢神经系统和血脑屏障中引发促炎级联反应。在大脑皮层、下丘脑、海马体等部位检测到了一些毒性作用。研究表明,炎症和氧化应激增加导致细胞凋亡,AgNPs 的主要神经毒性机制是 AgNPs 增加了银离子。

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