Metabolomic characteristics of hepatotoxicity in rats induced by silica nanoparticles.
Metabolomic characteristics of hepatotoxicity in rats induced by silica nanoparticles.
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DOI：
10.1016/j.ecoenv.2020.111496
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发表时间：
2020-10
影响因子：
6.8
通讯作者：
Mengqi Sun;Jingyi Zhang;Shuang Liang;Zhou Du;Jiangyan Liu;Zhiwei Sun;Junchao Duan
中科院分区：
文献类型：
--
作者：
Mengqi Sun;Jingyi Zhang;Shuang Liang;Zhou Du;Jiangyan Liu;Zhiwei Sun;Junchao Duan
二氧化硅纳米粒子（SiNPs）已成为环境健康和安全纳米技术中研究最广泛的纳米粒子之一。虽然许多研究致力于评估SiNPs的肝毒性，但目前无法通过鉴定代谢物的变化来预测肝脏脂质代谢紊乱的程度。本研究将40只雄性SD大鼠随机分为对照组和3个剂量组（1.8mg/kg体重、5.4mg/kg体重、16.2mg/kg体重），分别进行SiNPs腹腔注射。取肝组织进行脂质水平分析，血清进行血液生化分析。采用1H核磁共振技术结合多元统计分析，系统分析了大鼠肝组织代谢物的变化。SiNPs处理组大鼠血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和甘油三酯（TG）升高; SiNPs高剂量组TG和低密度脂蛋白胆固醇（LDL-C）明显升高，而肝组织中高密度脂蛋白胆固醇（HDL-C）呈下降趋势。正交偏最小二乘判别分析（OPLS-DA）评分图显示对照组和高剂量组之间存在不同的代谢特征（Q2= 0.495，R2 Y = 0.802，p = 0.037），共发现11种差异代谢产物。途径分析表明，SiNPs处理主要影响嘌呤代谢、葡萄糖-丙氨酸循环以及谷氨酸、半胱氨酸和天冬氨酸等多种氨基酸的代谢等10条代谢途径（影响值> 0.1，错误发现率（FDR）< 0.05）。结果表明，SiNPs染毒可引起大鼠肝脏脂质代谢紊乱，与脂质代谢相关的生化指标发生明显变化。SiNPs处理组大鼠代谢组学的明显变化主要发生在氨基酸、有机酸和核苷类化合物。
Silica nanoparticles (SiNPs) have become one of the most widely studied nanoparticles in nanotechnology for environmental health and safety. Although many studies have devoted to evaluating the hepatotoxicity of SiNPs, it is currently impossible to predict the extent of liver lipid metabolism disorder by identifying changes in metabolites. In the present study, 40 male Sprague-Dawley (SD) rats were randomly divided into control group and 3 groups with different doses (1.8 mg/kg body weight (bw), 5.4 mg/kg bw, 16.2 mg/kg bw), receiving intratracheal instillation of SiNPs. Liver tissue was taken for lipid level analysis, and serum was used for blood biochemical analysis. Then, the metabolites changes of liver tissue in rats were systematically analyzed using1H nuclear magnetic resonance (1H NMR) techniques in combination with multivariate statistical analysis. SiNPs induced serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglyceride (TG) elevation in treated groups; TG and low-density lipoprotein cholesterol (LDL-C) were significantly higher in SiNPs-treated groups of high-dose, however high-density lipoprotein cholesterol (HDL-C) showed a declining trend in liver tissue. The orthogonal partial least squares discriminant analysis (OPLS-DA) scores plots revealed different metabolic profiles between control and high-dose group (Q2= 0.495, R2Y = 0.802,p= 0.037), and a total of 11 differential metabolites. Pathway analysis indicated that SiNPs treatment mainly affected 10 metabolic pathways including purine metabolism, glucose-alanine cycle and metabolism of various amino acids such as glutamate, cysteine and aspartate (impact value > 0.1, false discovery rate (FDR) < 0.05). The result indicated that exposure to SiNPs caused liver lipid metabolism disorder in rats, the biochemical criterions related to lipid metabolism changed significantly. The obviously changed metabolomics in SiNPs-treated rats mostly occurred in amino acids, organic acids and nucleosides.