埃洛石纳米管的小鼠毒性研究

发布时间：2018-01-09 12:00

本文关键词：埃洛石纳米管的小鼠毒性研究　出处：《中国科学技术大学》2017年硕士论文　论文类型：学位论文

【摘要】：埃洛石(Al_2Si_2O_5(OH)_4·nH_2O)是一种具有中空管状结构的天然无机纳米粒子。因其丰富的产量、低廉的价格和独特的纳米结构,埃洛石被广泛应用于各个领域,比如陶瓷材料、高分子材料、污水处理。近年来,埃洛石作为化妆品添加剂、药物载体、超声造影剂、牙齿填充剂和骨植入剂的探索成为热门研究。在这些新的领域应用埃洛石之前,需要对其安全性进行评估。目前,人们对埃洛石的安全性没有进行系统评估。在已有的文献中,埃洛石的体外毒性研究主要针对细胞和微生物;而体内毒性方面,只有一篇文献报道了埃洛石对线虫的毒性。本文采用由超声破碎及粘度梯度分离法获得的长度可控的高纯埃洛石,研究了 30天重复灌胃给药后埃洛石对小鼠的毒性作用。主要包括以下内容:第一章,首先介绍了纳米材料的特点和影响纳米材料毒性的因素及其主要入侵途径,然后概述了埃洛石纳米管的特性和其在各个领域的广泛应用,最后总结了埃洛石毒性研究的已有数据,包括其体外毒性和体内毒性研究。第二章,首先分别对纯化前后的埃洛石纳米管(HNTs)进行了 TEM和XRF表征;然后探索了纯化后的HNTs在人工胃液、肠液、血液中的溶解度,并用DLS测定其水动力学半径;最后做了HNTs小鼠体内毒性预实验,2000 mg/kg BW剂量,灌胃给药7天。研究表明HNTs对小鼠肺产生了严重毒性,包括Al大量聚集,肺纤维化,小鼠的肝脏和肾脏Al、Si含量增加,且发生了组织病理变化,其中肝脏为细胞水肿、点状坏死和脂肪肝,肾脏为细胞水肿、肾小球萎缩。初步证明HNTs对小鼠的肺、肝、肾有毒性。第三章,研究了不同剂量(5,50,300 mg/kg BW)的HNTs对小鼠肺的毒性(30天)。结果证明5 mg/kg BW剂量对小鼠肺是安全的,没有发生组织病变、Al元素聚集、氧化应激。而50,300mg/kg BW剂量的HNTs引起肺部红细胞渗出、肺泡上皮细胞增生、纤维化,还发生了Al大量聚集和HNTs颗粒沉积。第四章,研究不同剂量(5,50,300 mg/kg BW)的HNTs对小鼠肝、肾的毒性(30天)。实验结果表明5 mg/kg BW剂量的HNTs对小鼠肝、肾无显著毒性,50,300 mg/kg BW剂量时HNTs会引起肝、肾的组织病变和功能障碍。同时,我们发现低剂量的HNTs可促进小鼠体重增长,高剂量对体重增长有抑制作用。
[Abstract]:Al2Si2O5S / s / s / s / nH2Os are natural inorganic nanoparticles with hollow tubular structures, due to their rich output. With its low price and unique nanostructure, Ellostone has been widely used in various fields, such as ceramic materials, polymer materials, sewage treatment. In recent years, Ellostone has been used as cosmetic additive and drug carrier. The exploration of ultrasound contrast agents dental fillers and bone implants has become a hot topic. The safety of Ellostone needs to be evaluated before it can be used in these new areas. There has been no systematic assessment of the safety of Ellostone. In the literature, in vitro toxicity studies have been focused on cells and microbes; However, in vivo toxicity, only one document reported the toxicity of Elomite to nematodes. In this paper, the length controlled high purity Elosterite was obtained by ultrasonic crushing and viscosity gradient separation. The toxic effects of Ellostone on mice after repeated oral administration for 30 days were studied. The main contents were as follows: chapter 1. The characteristics of nanomaterials, the factors affecting the toxicity of nanomaterials and their main invasion approaches are introduced. Then, the characteristics of Ellosite nanotubes and their wide applications in various fields are summarized. Finally, the existing data of the study on the toxicity of Elomite are summarized, including in vitro and in vivo toxicity studies. Chapter 2. Firstly, TEM and XRF were used to characterize the HNTs before and after purification. Then, the solubility of purified HNTs in artificial gastric juice, intestinal fluid and blood was explored, and its hydrodynamic radius was determined by DLS. Finally, the HNTs mice in vivo toxicity pretest of 2000 mg/kg BW dose, intragastric administration of 7 days. The study showed that HNTs induced severe toxicity to the lungs of mice, including a large number of Al accumulation. With pulmonary fibrosis, the contents of Albumin Si in liver and kidney of mice increased, and histopathological changes occurred. The liver was cell edema, punctate necrosis and fatty liver, and kidney was cell edema. Glomerular atrophy. HNTs was proved to be toxic to lung, liver and kidney in mice. The results showed that the dose of 5 mg/kg BW was safe for the lung of mice, and no pathological changes occurred. The concentration of Al elements, oxidative stress, and 50 ~ 300mg / kg BW HNTs caused pulmonary erythrocyte exudation, alveolar epithelial cell proliferation, fibrosis. A large number of Al aggregations and HNTs particle deposition were also observed in chapter 4th. The effects of different doses of HNTs on the liver of mice were studied. The results showed that the dose of 5 mg/kg BW HNTs had no significant toxicity to the liver and kidney of mice. At the dose of 300 mg/kg BW, HNTs can cause liver and kidney lesions and dysfunction. At the same time, we found that low dose of HNTs can promote weight gain in mice. High doses have an inhibitory effect on weight gain.
【学位授予单位】：中国科学技术大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TB383.1

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