中国新药杂志

基于UPLC-MS研究纳米二氧化钛对成年小鼠血浆代谢谱的影响

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姬海南 ¹ , 康辉 ² , 李海山 ¹ , 宋乃宁 ¹ , 徐宝梁 ¹ , 赵潺 ¹ , 李文涛 ¹ , 沈国林 ¹

中国新药杂志 | 实验研究 2021,30(14): 1323-1333

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中国新药杂志 |实验研究 2021 , 30 (14) : 1323 -1333

基于UPLC-MS研究纳米二氧化钛对成年小鼠血浆代谢谱的影响

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姬海南¹, 康辉², 李海山¹, 宋乃宁¹, 徐宝梁¹, 赵潺¹, 李文涛¹, 沈国林¹

作者信息

¹中国检验检疫科学研究院化学品安全研究所，北京　100176

²河南中医药大学，郑州　450046

通讯作者:

沈国林，男，博士，副研究员，主要从事化学品安全研究。E-mail：shengl@aqsiqch.ac.cn。

李文涛，男，博士，副研究员，主要从事产品质量安全研究。E-mail：liwt@caiq.gov.cn。

作者简介:

姬海南，男，硕士，助理研究员，主要从事化学品安全研究。E-mail：1446678196@qq.com。

Investigation on the effect of nano-TiO₂ on the plasma metabolic spectrum in mice based on UPLC-MS

Hai-nan JI¹, Hui KANG², Hai-shan LI¹, Nai-ning SONG¹, Bao-liang XU¹, Chan ZHAO¹, Wen-tao LI¹, Guo-lin SHEN¹

Affiliations

¹Institute of Chemicals Safety, Chinese Academy of Inspection and Quarantine, Beijing 100176, China

²College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China

出版时间: 2021-07-30

文章导航

摘要

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目的：

观察不同染毒剂量的纳米二氧化钛（TiO₂）对C57BL/6成年小鼠血浆代谢谱的变化，探讨其产生毒性效应可能的作用机制，并尝试寻求其毒性相关生物靶点。

方法：

运用纳米TiO₂制备不同染毒剂量的小鼠模型，将小鼠随机分为对照组及10，30，100和300 mg·kg^-1组。利用UPLC-MS技术结合主成分分析、偏最小二乘分析等方法对血浆数据进行分析，鉴定出潜在生物标志物，通过变量对模型的重要性（variable important in projection，VIP）及非参数检验筛选差异代谢物；运用Pathway Analysis数据库对差异标志物进行拓扑分析。

结果：

从血浆中筛选出35种差异代谢物，发现纳米TiO₂发挥干预作用可能与亚油酸代谢、鞘脂代谢、缬氨酸、亮氨酸和异亮氨酸的生物合成、组氨酸代谢、花生四烯酸代谢、烟酸酯和烟酰胺代谢、甘油磷脂代谢等通路有关。

结论：

纳米TiO₂经过28 d染毒后，所产生的毒性作用机制可能与体内氨基酸代谢、脂质类代谢异常相关。

关键词

纳米二氧化钛 / 代谢组学 / 血浆 / 生物靶点

Abstract

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Objective:

To investigate the changes of the plasma metabolic spectrum of C57BL/6 young mice treated with different doses of nano-TiO₂, explore the possible mechanism of its toxic side effects, and identify its toxicity-related biological targets.

Methods:

Mice were randomly assigned to receive nano-TiO₂ at doses of 0 (control group), 10, 30, 100, or 300 mg·kg^-1. The plasma data were analyzed using UPLC-MS technology combined with principal component and partial least squares analyses. The results revealed differences between the control group and each nano-TiO₂ group, with the effect becoming more pronounced with increasing doses. Topological analysis of the different metabolites was conducted using the Pathway Analysis database.

Results:

In total, 35 different metabolites were screened from plasma, and Nano-TiO₂ treatment was revealed to affect linoleic acid metabolism, biosynthesis of valine, leucine and isoleucine, sphingolipid metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, histidine metabolism, and other pathways.

Conclusion:

The results indicated that the toxicity mechanism of Nano-TiO₂ after 28 days of exposure may be related to abnormal amino acid and lipid metabolism.

Key words

nano-TiO₂ / metabolomics / plasma / biological targets

引用本文

姬海南, 康辉, 李海山, 宋乃宁, 徐宝梁, 赵潺, 李文涛, 沈国林. 基于UPLC-MS研究纳米二氧化钛对成年小鼠血浆代谢谱的影响. 中国新药杂志, 2021 , 30 (14) : 1323 -1333 .

Hai-nan JI, Hui KANG, Hai-shan LI, Nai-ning SONG, Bao-liang XU, Chan ZHAO, Wen-tao LI, Guo-lin SHEN. Investigation on the effect of nano-TiO₂ on the plasma metabolic spectrum in mice based on UPLC-MS[J]. Chinese Journal of New Drugs, 2021 , 30 (14) : 1323 -1333 .

基金

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国家重点研发计划资助项目(2017YFF0211201)
国家市场监督管理总局业务费化学品质量安全检测能力提升专项资金资助项目(15002000000019)
公益性科研院所基本科研业务费专项资金资助项目(2019JK027; 2018JK023; 2018JK021; 2017JK047)
基本科研业务费专项资助项目(2020JK035)
婴幼儿化妆品防腐体系安全评价研究

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2021年第30卷第14期

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首发时间：2026-10-28
出版时间：2021-07-30

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录用日期：2020-11-27

基金

国家重点研发计划资助项目(2017YFF0211201)

国家市场监督管理总局业务费化学品质量安全检测能力提升专项资金资助项目(15002000000019)

公益性科研院所基本科研业务费专项资金资助项目(2019JK027; 2018JK023; 2018JK021; 2017JK047)

基本科研业务费专项资助项目(2020JK035)

婴幼儿化妆品防腐体系安全评价研究

作者信息

¹中国检验检疫科学研究院化学品安全研究所，北京　100176

²河南中医药大学，郑州　450046

通讯作者:

沈国林，男，博士，副研究员，主要从事化学品安全研究。E-mail：shengl@aqsiqch.ac.cn。

李文涛，男，博士，副研究员，主要从事产品质量安全研究。E-mail：liwt@caiq.gov.cn。

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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