1H NMR-based metabolomics study on repeat dose toxicity of fine particulate matter in rats after intratracheal instillation.
1H NMR-based metabolomics study on repeat dose toxicity of fine particulate matter in rats after intratracheal instillation.
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DOI：
10.1016/j.scitotenv.2017.02.149
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发表时间：
2017-07
期刊：
影响因子：
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通讯作者：
Yannan Zhang;Hejing Hu;Yanfeng Shi;Xiaozhe Yang;Lige Cao;Jing Wu;C. Asweto;Lin Feng;Junchao Duan
中科院分区：
文献类型：
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作者：
Yannan Zhang;Hejing Hu;Yanfeng Shi;Xiaozhe Yang;Lige Cao;Jing Wu;C. Asweto;Lin Feng;Junchao Duan
大气细颗粒物（PM2.5）的全身代谢效应和毒性机制尚不清楚。为了探讨PM2. 5的毒性机制，本研究采用基于核磁共振（NMR）的代谢组学方法，对大鼠肺内注入PM2. 5后内源性代谢变化及可能受影响的代谢途径进行了研究。还进行了肝脏和肾脏组织病理学检查。化学表征表明，PM2.5是一个复杂的元素混合物。组织学检查显示PM2.5处理组大鼠肝细胞水肿，肾小球萎缩。本文采用1H NMR技术结合多元统计分析，系统分析了大鼠血清和尿液中代谢物的变化。PM2.5处理组大鼠血清中乳酸、丙氨酸、二甲基甘氨酸、肌酸、甘氨酸和组氨酸水平显著降低，尿液中柠檬酸、精氨酸、马尿酸、尿囊素水平显著升高，而丙苏氨酸、乳酸、丙氨酸、乙酸、琥珀酸、三甲胺、甲酸水平显著降低。PM2.5影响的代谢途径主要有甘氨酸、丝氨酸和苏氨酸代谢、乙醛酸和二羧酸代谢、柠檬酸循环（TCA循环）、氮代谢和甲烷代谢。本研究为评价PM2. 5的毒性提供了重要信息，并表明代谢组学方法可以作为理解复杂环境污染物毒性机制的工具。
Systemic metabolic effects and toxicity mechanisms of ambient fine particulate matter (PM2.5) remain uncertain. In order to investigate the mechanisms in PM2.5toxicity, we explored the endogenous metabolic changes and possible influenced metabolic pathways in rats after intratracheal instillation of PM2.5by using a1H nuclear magnetic resonance (NMR)-based metabolomics approach. Liver and kidney histopathology examinations were also performed. Chemical characterization demonstrated that PM2.5was a complex mixture of elements. Histopathology showed cellular edema in liver and glomerulus atrophy of the PM2.5treated rats. We systematically analyzed the metabolites changes of serum and urine in rats using1H NMR techniques in combination with multivariate statistical analysis. Significantly reduced levels of lactate, alanine, dimethylglycine, creatine, glycine and histidine in serum, together with increased levels of citrate, arginine, hippurate, allantoin and decreased levels of allthreonine, lactate, alanine, acetate, succinate, trimethylamine, formate in urine were observed of PM2.5treated rats. The mainly affected metabolic pathways by PM2.5were glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, citrate cycle (TCA cycle), nitrogen metabolism and methane metabolism. Our study provided important information on assessing the toxicity of PM2.5and demonstrated that metabolomics approach can be employed as a tool to understand the toxicity mechanism of complicated environmental pollutants.