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纳米级铜颗粒经鼻腔滴注后对小鼠的潜在健康影响及其在小鼠体内的转运

Potential health impact on mice after nasal instillation of nano-sized copper particles and their translocation in mice.

作者信息

Liu Yang, Gao Yuxi, Zhang Lili, Wang Tiancheng, Wang Jiangxue, Jiao Fang, Li Wei, Liu Ying, Li Yufeng, Li Bai, Chai Zhifang, Wu Gang, Chen Chunying

机构信息

Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Lab of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, PR China.

出版信息

J Nanosci Nanotechnol. 2009 Nov;9(11):6335-43. doi: 10.1166/jnn.2009.1320.

DOI:10.1166/jnn.2009.1320
PMID:19908531
Abstract

The purpose of this study is to evaluate the overall toxicity of nasal instilled nanoscale copper particles (23.5 nm) in mice. Pathological examination, target organs identification, and blood biochemical assay of experimental mice were carried out in comparison with micro-sized copper particles (17 microm). However, only in the high-dose group of copper nanoparticles (40 mg/kg body weight instilled for three times in one week), the body weight of mice were retarded and significant pathological changes were observed. There were hydropic degeneration around the central vein and the spotty necrosis of hepatocytes in the liver and swelling in the renal glomerulus, while, severe lesion associated with the decreased number of olfactory cells and the dilapidated laminated structure were also observed in the olfactory bulb. The serum biochemical assay also indicated the sign of renal and hepatic lesion. However, there were no obvious pathological and physiological damages in the mice after instilling different-sized copper nanoparticles with low dose of 1 mg/kg body weight. The retention and distribution of copper in various tissues show that the liver, kidneys and olfactory bulb are the main accumulated tissues for copper particles, which were determined by high sensitive element-specific technique of ICP-MS. The copper contents of the liver, kidneys and the olfactory bulb increase significantly at the group of 40 mg/kg compared to the control group, which is in agreement with the histological changes. Therefore, the data indicate that nasal inhaled copper particles at very high dosage can translocate to other organs and tissues and further induce certain lesions. The present results are helpful to get better understanding of the risk assessment and evaluation for copper nanoparticles.

摘要

本研究的目的是评估经鼻腔滴注纳米级铜颗粒(23.5纳米)对小鼠的整体毒性。对实验小鼠进行了病理检查、靶器官鉴定和血液生化检测,并与微米级铜颗粒(17微米)进行了比较。然而,仅在铜纳米颗粒高剂量组(一周内三次滴注40毫克/千克体重)中,观察到小鼠体重增长迟缓且出现了明显的病理变化。肝脏中央静脉周围出现水样变性,肝细胞出现点状坏死,肾小球肿胀,同时,嗅球中也观察到与嗅细胞数量减少和层状结构破损相关的严重病变。血清生化检测也显示出肾脏和肝脏损伤的迹象。然而,在以1毫克/千克体重的低剂量滴注不同尺寸的铜纳米颗粒后,小鼠没有明显的病理和生理损伤。铜在各种组织中的滞留和分布表明,肝脏、肾脏和嗅球是铜颗粒的主要蓄积组织,这是通过电感耦合等离子体质谱仪(ICP-MS)的高灵敏度元素特异性技术测定的。与对照组相比,40毫克/千克组肝脏、肾脏和嗅球中的铜含量显著增加,这与组织学变化一致。因此,数据表明,极高剂量经鼻腔吸入的铜颗粒可转移至其他器官和组织并进一步诱发某些病变。目前的结果有助于更好地理解铜纳米颗粒的风险评估和评价。

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