摘要:
为探究全氟辛烷磺酸(PFOS)对水生动物肝脏的慢性毒性毒害机制,寻找其肝脏慢性毒性相关的潜在标志物,运用气相色谱-质谱联用仪代谢组学方法研究暴露于PFOS中斑马鱼肝脏内源性代谢物的变化,寻找显著性差异代谢物及相关通路。实验分为4组:对照组及PFOS浓度分别为10、100、250 μg·L-1的实验组,每组20尾斑马鱼,实验时长40 d。结果显示,与对照组相比,PFOS浓度为10 μg·L-1的斑马鱼肝脏中筛选出4种发生显著性变化的代谢物,分别为牛磺酸、磷酸乙酰胺、β-D-葡萄糖、油酸,涉及4条代谢通路,即牛磺酸和亚牛磺酸代谢、鞘脂代谢、甘油磷脂代谢、糖酵解或葡萄糖生成。100 μg·L-1浓度组的斑马鱼肝脏中筛选出5种,包括牛磺酸、β-D-葡萄糖、棕榈酸、油酸、胆固醇,涉及5条代谢通路,即原代胆汁酸生物合成、牛磺酸和亚牛磺酸代谢、类固醇生物合成、类固醇激素生物合成、糖酵解或葡萄糖生成。250 μg·L-1浓度组的斑马鱼肝脏中筛选出5种,即牛磺酸、β-D-葡萄糖、乳酸、甘油-3-磷酸、磷酸乙酰胺,涉及5条代谢通路:牛磺酸和亚牛磺酸代谢、甘油磷脂代谢、甘油脂代谢、鞘脂代谢、糖酵解或葡萄糖生成。根据筛选出的差异代谢物生理功能和其涉及代谢通路分析,推测PFOS主要通过影响牛磺酸和亚牛磺酸代谢、糖酵解或葡萄糖生成及一些脂类代谢从而对斑马鱼肝脏产生毒性效应,其中牛磺酸、葡萄糖与油酸这3种代谢物可作为斑马鱼受PFOS胁迫肝脏代谢异常的潜在标记物。
Abstract:
In order to explore the mechanism of chronic toxicity of perfluorooctane sulfonate (PFOS) on livers of aquatic animals and to find potential markers related to chronic liver toxicity, a gas chromatography-mass spectrometry metabolomics method was used in this study, so as to study the effects of PFOS exposure on changes in liver endogenous metabolites and to discover metabolites that are of significant differences and their related pathways in Danio rerio. Four groups were set up including one control group and three experimental groups with PFOS con- centration at 10, 100 and 250 μg·L-1, respectively. 20 pieces of Danio rerio were cultured in each group, and the experiment lasted for 40 days. The results showed that compared with the control group, four metabolites including taurine, phosphoric acid amide, β-D-glucose and oleic acid were identified from the liver of Danio rerio of the group with PFOS concentration at 10 μg·L-1 and four metabolic pathways including taurine and hypotaurine metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and glycolysis or gluconeogenesis were involved. Five metabolites including taurine, β-D-glucose, palmitic acid, oleic acid and cholesterol, were identified from the liver of zebrafish of the group with PFOS concentration at 100 μg·L-1, and five metabolic pathways including primary bile acid biosynthesis, taurine and hypotaurine metabolism, steroid biosynthesis, steroid hormone biosynthesis and glycolysis or gluconeogenesis were involved. Four metabolites including taurine, β-D-glucose, lactic acid, glycerol-3-phosphate and phosphoacetamide, were identified from the liver of Danio rerio group with PFOS concentration at 250 μg·L-1, and five metabolic pathways including taurine and hypotaurine metabolism, glycerophospholipid metabolism, glycerolipid metabolism, sphingolipid metabolism and glycolysis or gluconeogenesis were invloved. Based on the physiological functions of the identified metabolites and the analysis of their metabolic pathways, it was speculated that PFOS exerts toxic effects on Danio rerio liver mainly by interfering the met- abolic pathways of taurine and hypotaurine, glycolysis or glucose production, and some lipid metabolism. Among them, the three metabolites including taurine, glucose and oleic acid can be used as potential markers for Danio rerio liver metabolism abnormalities induced by PFOS.
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