纳米TiO2对幼年小鼠血浆代谢谱影响的代谢组学研究
Metabonomics Study on the Effect of Nano-TiO2 on the Plasma Metabolism Spectrum of Young Mice
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摘要: 观察不同染毒剂量的纳米TiO2对ICR幼年小鼠血浆代谢谱变化的影响，寻找潜在的毒性效应的生物标志物。将幼年小鼠随机分为对照组以及10、30、100和300 mg·kg-1不同纳米TiO2染毒组进行28 d短期毒性试验，利用代谢组学技术初步筛选出TiO2毒性作用潜在的生物标志物，运用KEGG数据库对生物标志物进行拓扑分析；并利用靶向定量技术检测血浆胆酸、去氧胆酸、熊去氧胆酸和牛磺胆酸的含量变化，从而探究TiO2毒性作用相对应的生物标志物。从血浆中筛选出49种差异代谢物，发现纳米TiO2染毒后主要导致磷脂类及胆汁酸类化合物的异常。小鼠经过纳米TiO2 28 d染毒后，其毒性作用可能与磷脂代谢及胆汁酸代谢异常相关，血浆中的胆汁酸可以作为纳米TiO2产生肝脏毒性作用的生物标志物。Abstract: Changes in the plasma metabolism of young ICR mice after exposure to nano-TiO2 at different doses were measured to investigate the mechanism of its toxic side-effects and to identify its toxicity-related biological targets. Mice were assigned randomly to control group and nano-TiO2 (10, 30, 100, or 300 mg·kg-1) exposure groups. Plasma data were analyzed using metabonomics technology to identify potential biomarkers. Topology of biomarkers was determined using the KEGG database. Contents of cholic acid, deoxycholic acid, ursodeoxycholic acid and taurocholic acid in plasma were measured by targeted quantitative methods to find the biomarkers corresponding to the toxic effects of TiO2. Forty-nine metabolites were screened from plasma. The toxicity of nano-TiO2 resulted mainly from an abnormality of phospholipids and bile-acid compounds. The toxicity of nano-TiO2 in mice after 28 d exposure may be related to the abnormal metabolism of phospholipids and bile-acid compounds.
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Key words:
- nano-TiO2 /
- young mice /
- metabonomics /
- plasma /
- bile acid /
- phospholipid metabolism
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