血清代谢组学研究长期低剂量PFOS暴露对大鼠的毒性效应

Serum Metabolomics Analysis Reveals Toxicity Induced by Long Term Low-Dose PFOS Exposure in Rats

全氟辛烷磺酸(perfluorooctane sulfonate,PFOS)是一种具有高生物蓄积性的持久性有机污染物,其环境暴露与多种不良健康效应有关。然而,慢性低剂量PFOS暴露对机体代谢网络的影响目前尚不清楚。本研究将大鼠暴露于0.015、0.15、1.5 mg·kg^(-1)的PFOS 2个月后,采用超高效液相色谱-质谱联用法(UPLC-MS)分析其血清代谢组,并比较暴露组与对照组的代谢谱差异,筛选差异代谢物及相关代谢通路。结果显示,暴露后大鼠血清中的PFOS含量随暴露剂量的增大显著上升,说明PFOS可在大鼠体内蓄积。此外,在各暴露组中共筛选出9种共同差异代谢物,其中5种代谢物在PFOS暴露后含量降低,4种代谢物水平上升。这些差异代谢物主要涉及脂质代谢和嘌呤代谢等代谢途径。所有单一代谢物的ROC曲线下面积(AUC)均>0.8,7种以上(含7种)代谢物组合时的AUC为1,表明这些代谢标志物对于PFOS暴露具有较高的判别能力。本研究结果可为环境低剂量PFOS暴露的健康风险评估及毒性机制解析提供一定的参考依据。

Perfluorooctane sulfonate(PFOS)is one of the typical per uoroalkyl substances(PFASs)widely used in different household and industrial products.At present,the accumulation of PFOS has been found in a variety of animals.It was also found to be associated with developmental defects,abortion,neonatal mortality,liver function,endocrine disruption and tumorigenesis.At present,there are rare studies using metabolomics technology to study the changes in serum metabolomics profile and the related metabolic pathways after chronic low-level PFOS exposure in mammals.In this study,forty rats were randomly divided into 0(control),0.015,0.15 and 1.5 mg·kg^(-1) PFOS exposure groups.Serum samples were collected after two months of exposure,and the metabolic fingerprints in serum were measured by ultra performance liquid chromatograph-mass spectrometry(UPLC-MS).Multivariate statistical analysis was used to compare the differences in metabolic profiles between each exposure group and the control group,and to screen out the common differential metabolites and metabolic pathways.Compared with the control,the serum concentrations of PFOS in rats after exposure were dose-dependently increased to 3.774,13.584 and 69.75 ng·μL^(-1),respectively,indicating that PFOS can accumulate in the serum,which may lead to metabolic changes in rats.A total of 9 common differential metabolites were screened for exposure groups,mainly involving in lipid and purine metabolism.Among them,the contents of 5 metabolites decreased and 4 metabolites increased after PFOS exposure.ROC analysis showed that the area under the curve(AUC)of all single metabolites was greater than 0.8,and the AUC of the combination of at least 7 metabolites was 1.The results of this study are expected to provide a new clue to reveal the toxic mechanism of PFOS,and to develop useful biomarkers for the health risk assessment of environmental PFOS exposure.