基于^(1)H NMR的代谢组学方法研究F-53B暴露对大鼠血清代谢表型的影响

Elucidation of F-53B exposure on serum metabolic phenotype in SD rat by NMR-based metabonomic analysis

氯化多氟醚磺酸盐(chlorinated polyfluorinated ether sulfonic acids,F-53B)是全氟烷基磺酸(perfluorooctane sulfonate,PFOS)的替代品.大量毒理学实验证明F-53B具有类似PFOS的生物持久性及毒性,但目前国内外尚未报道过关于F-53B的生物代谢扰动机制研究.本研究基于^(1)H-NMR分析了F-53B(50μg·kg^(-1)·d^(-1))暴露28 d后的大鼠血清代谢扰动情况,结合多元统计分析,分析相关差异代谢物和代谢通路变化.暴露组检测到17个差异代谢物,主要包括氨基酸代谢物和碳水化合物代谢物.3条氨基酸代谢通路受到显著影响,包括丙氨酸、天冬氨酸和谷氨酸代谢,组氨酸代谢,苯丙氨酸,酪氨酸和色氨酸生物合成.糖代谢和脂质代谢受到影响.研究结果表明大鼠暴露于F-53B后可能会影响血清的氧化应激反应,引发炎症,心血管疾病,糖尿病和高血压,引起神经毒性且抑制大脑发育.本研究对F-53B暴露产生的代谢扰动进行深入且全面的探究,为评估F-53B的健康风险提供了科学依据.

Chlorinated polyfluorinated ether sulfonic acid(trade name,F-53B)is an alternative to perfluorooctane sulfonate(PFOS).A large number of toxicological experiments have proved that F53B has biological persistence and toxicity similar to PFOS,but there is no study on the biological metabolic disturbance mechanism research of F-53B.In this study,SD rats were orally exposed to 50μg·kg^(-1)·d^(-1) F-53B for 28 days to evaluate the serum metabolic disturbances of F-53B by ^(1)H-NMR serum metabolomics and then combined with multivariate statistical analysis,the relevant differential metabolites and metabolic pathway changes were analyzed.Results showed that 17 metabolites(mainly including amino acid metabolites and carbohydrate metabolites)and 3 metabolic pathways(alanine,aspartic acid,and glutamate metabolism;histidine metabolism;phenylalanine,tyrosine,and tryptophan biosynthesis)were disturbed by F-53B exposure.Sugar metabolism and lipid metabolism were affected.The results of the study indicated that exposure to F-53B may affect the oxidative stress response of the serum,cause inflammation,cardiovascular disease,diabetes,and hypertension,cause neurotoxicity and inhibit brain development.This study provides an in-depth and comprehensive exploration of the metabolic disturbances caused by F-53B exposure,and a scientific basis for assessing the health risks of F-53B.