壬基酚和辛基酚联合暴露的血清代谢特征及生物标志物

运用代谢组学方法分析了壬基酚（NP）和辛基酚（OP）联合暴露后大鼠血清代谢成分变化，雄性SD大鼠随机分为对照组、壬基酚和辛基酚（联合染毒低剂量组（25mg/kg NP+25mg/kg OP）及高剂量组（75mg/kg NP+75mg/kg OP）.连续灌胃7d后处死.通过超高效液相色谱-飞行时间质谱（UPLC/QTOF-MS）技术获得大鼠血清的代谢指纹图谱，通过主成分分析观察了联合染毒的剂量-效应，通过t检验筛选潜在的生物标志物，并结合代谢物数据库检索对潜在的生物标志物进行鉴定.结果显示，对照组、高、低剂量组各组间代谢谱有明显差别，且随着染毒剂量的增加毒性增强，表现为剂量-效应关系.联合染毒后的血清代谢物中，含量升高的有牛黄胆酸及1-棕榈酰基磷脂酰胆碱，含量降低的有酪氨酸、5-尿苷一磷酸及硫脑苷酯，提示染毒可能对内分泌系统、心血管系统、神经系统以及核苷酸合成、糖代谢、磷脂代谢等产生不良影响.

Serum metabolism characteristics and biomarker of joint exposure to nonylphenol and octylphenol

The metabonomics method was employed to investigate the changes in serum metabolic components of Sprague Dawley rats after combined exposure to nonylphenol (NP) and octylphenol (OP). The male rats were randomly divided into control group, low-dose combined exposure group (25mg/kg NP+25mg/kg OP) and high-dose combined exposure group (75mg/kg NP+75mg/kg OP). The rats were treated by gavage once a day for 7 days, and then killed. The metabolic fingerprinting of rat serum was obtained by ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC/TOF-MS). Dose-response toxicity was observed based on the principle components analysis (PCA). Meanwhile, the potential biomarkers were screened out according to t-test. The results showed that there was a significant difference in the metabolic profile among the control group, high and low dose groups, and with the increase of exposure dose, the toxicity was enhanced, which showed a dose-effect relationship. Meanwhile, the contents of taurocholic acid and 1-Palmitoyllysophosphatidylcholine increased while the contents of tyrosine, uridine-5'-monophosphate and sulfatide decreased under combined exposure to NP and OP. It is suggested that NP and OP exposure may have adverse effects on the endocrine system, cardiovascular system, nervous system, nucleotide synthesis, sugar and phospholipid metabolism.