纳米氧化锌在神经元细胞系中的毒理机制研究

发布时间：2018-03-18 21:25

本文选题：纳米材料　切入点：氧化锌　出处：《南方医科大学》2017年博士论文　论文类型：学位论文

【摘要】：氧化锌是应用非常广泛、具有悠久历史的口腔材料之一。随着纳米技术的快速发展,纳米级氧化锌的应用越来越多,生产者、消费者以及相关研究人员的接触暴露及后续相关的毒性效应也因此备受关注。有研究表明,纳米颗粒能够穿透大脑屏障或通过嗅-脑通路转运进入大脑,然而对于纳米材料暴露而诱发的大脑相关毒理损伤的机制尚不完全明确。本课题组的前期研究发现,孕鼠暴露于纳米氧化锌材料后导致胎鼠大脑发育异常,且相关功能损伤。本研究中使用BV2细胞系和PC12细胞系,建立小胶质细胞和神经元细胞研究模型,通过给予不同浓度的纳米氧化锌或氯化锌干预,评估诱导产生的细胞毒性;进一步探讨不同浓度剂量下两种细胞毒理特性的差异;同时探索纳米氧化锌的离子释放效应在其毒理机制中的扮演的角色。本研究成果将为进一步探究纳米材料诱导大脑功能损伤的毒理机制提供可有力的帮助。第一章:纳米氧化锌颗粒对BV2细胞、PC12细胞的细胞毒性作用通过表征检测获取纳米氧化锌颗粒的相关材料信息,成功获取小胶质细胞系,并诱导PC12细胞神经元样改变。实验证实,纳米氧化锌颗粒在不同浓度梯度下展现不同的毒性,其中凋亡、自噬是主要毒理效应之一。另外,通过NAC干预证实氧化应激在纳米氧化锌颗粒诱导的毒理机制中起到关键作用。第二章:锌离子在纳米氧化锌颗粒诱导的细胞生理效应中的作用纳米氧化锌在不同的浓度以及酸性环境下有不同强度的离子释放效应,酸性环境能导致纳米氧化锌的大量溶解。纳米氧化锌的离子释放效应在诱导细胞产生毒性的毒理机制中扮演了关键作用。第三章:低浓度纳米氧化锌颗粒对BV2细胞促增殖作用以及相关机制研究低浓度纳米氧化锌颗粒能通过调节细胞周期促进细胞增殖,锌离子释放效应在其中扮演了关键作用。另外,纳米氧化锌颗粒促进ERK和Akt信号通路磷酸化水平,而这两个通路对细胞增殖具有明显调节作用。第四章:毒性剂量纳米氧化锌颗粒对BV2细胞、PC12细胞的毒性作用毒性剂量纳米氧化锌颗粒能够诱导细胞骨架系统的破坏、细胞内线粒体的功能损伤。综上,本研究对纳米氧化锌颗粒的毒理效应及相关机制进行了评估,进一步探讨了纳米氧化锌进入细胞后的生理机制,为未来纳米氧化锌的广泛应用提供可靠的信息支持。
[Abstract]:Zinc oxide is one of the most widely used oral materials with a long history. The exposure of consumers and related researchers and the associated toxic effects are also of concern. Some studies have shown that nanoparticles can penetrate the brain barrier or transport through the olfactory brain pathway into the brain. However, the mechanism of brain related toxicological damage induced by exposure to nanomaterials is not completely clear. In this study, BV2 cell line and PC12 cell line were used to establish the model of microglia and neuron cells. The cytotoxicity was evaluated by different concentrations of nano-zinc oxide or zinc chloride. The difference of toxicological characteristics between two kinds of cells at different concentrations was discussed. At the same time, the role of ion release effect of nano-zinc oxide in its toxicological mechanism is explored. This study will be helpful to further explore the toxicological mechanism of brain function damage induced by nanomaterials. Chapter: the cytotoxic effect of nano-zinc oxide particles on BV2 cells of PC12 cells. Microglial cell lines were successfully obtained and PC12 neuron-like changes were induced. The results showed that nano-ZnO particles exhibited different toxicity under different concentration gradient, and apoptosis and autophagy were one of the main toxicological effects. NAC intervention confirmed that oxidative stress plays a key role in the toxicological mechanism induced by nano-zinc oxide particles. Chapter 2: the role of zinc ions in the cellular physiological effects induced by nano-zinc oxide particles. Have different ionic release effects in acidic environment, Acidic environment can lead to a large amount of dissolution of nano-zinc oxide. The ion release effect of nano-zinc oxide plays a key role in the toxicological mechanism of inducing cytotoxicity. Chapter 3: low concentration nano-zinc oxide particles on BV2 fine. Study on the Proliferous effect of low concentration nanometer Zinc oxide particles can promote Cell Proliferation by regulating Cell cycle. Zinc ion release plays a key role in this process. In addition, zinc oxide nanoparticles promote phosphorylation of ERK and Akt signaling pathways. In Chapter 4th: toxic dose of nano-zinc oxide particles can induce the destruction of cytoskeleton system in BV2 cells. In summary, the toxicological effects and related mechanisms of nano-zinc oxide particles were evaluated, and the physiological mechanism of nano-zinc oxide particles after entering cells was further discussed. It provides reliable information support for the wide application of nanometer zinc oxide in the future.
【学位授予单位】：南方医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R783.1

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