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单壁碳纳米管对 PC12 细胞的细胞毒性。

Cytotoxicity of single-walled carbon nanotubes on PC12 cells.

机构信息

School of Biological Science & Technology, State Key Laboratory of Fine Chemicals, Dalian University of Technology, Ganjingzi District, Dalian, PR China.

出版信息

Toxicol In Vitro. 2011 Feb;25(1):242-50. doi: 10.1016/j.tiv.2010.11.010. Epub 2010 Nov 19.

Abstract

The increasing use of carbon nanotubes (CNTs) in biomedical applications underlines the importance of its potential toxic effects to human health. In the present study, we first exposed PC12 cells, a commonly used in vitro model for neurotoxicity study, to two kinds of commercially available single-walled carbon nanotubes (SWCNTs), to investigate the effect of SWCNTs on nervous system in vitro. The decrease of PC12 cells viability was time and dose-dependent with exposure to SWCNTs demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release and morphological observation. Flow cytometry analysis showed that the PC12 cells' cycle was arrested in the G2/M phase, and their apoptotic rate induced by SWCNTs was dose-dependent. Further studies revealed SWCNTs decreased mitochondrial membrane potential (MMP), induced the formation of reactive oxygen species (ROS) and increased the level of lipid peroxide and decreased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and the content of glutathione (GSH) in a time and dose-dependent manner. These findings reveal that SWCNTs may induce oxidative stress to nervous system in vivo, causing the occurrence of diseases related to cellular injuries of neuronal cells, such as neurodegenerative disorders, and demonstrating the necessity of further research in vivo.

摘要

越来越多的碳纳米管(CNTs)在生物医学应用中的使用凸显了其对人类健康潜在毒性作用的重要性。在本研究中,我们首先将 PC12 细胞(一种常用于神经毒性研究的体外模型)暴露于两种市售的单壁碳纳米管(SWCNTs)中,以研究 SWCNTs 对体外神经系统的影响。MTT 分析、乳酸脱氢酶(LDH)释放和形态观察结果表明,SWCNTs 暴露会导致 PC12 细胞活力随时间和剂量的减少而减少,从而导致细胞活力下降。流式细胞术分析表明,PC12 细胞的细胞周期被阻滞在 G2/M 期,SWCNTs 诱导的细胞凋亡呈剂量依赖性。进一步的研究表明,SWCNTs 降低了线粒体膜电位(MMP),诱导了活性氧(ROS)的形成,并增加了脂质过氧化物的水平,降低了超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)的活性和谷胱甘肽(GSH)的含量,呈时间和剂量依赖性。这些发现表明,SWCNTs 可能会引起体内神经系统的氧化应激,导致与神经元细胞细胞损伤相关的疾病的发生,如神经退行性疾病,并证明了在体内进行进一步研究的必要性。

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