双酚F暴露后对小鼠肝脏神经递质代谢的影响  

Bisphenol F exposure disrupts metabolism of neurotransmitters in mouse liver

作　　者：曹辉[1] 余正 范一纯 林雨欣 王军 高蓉[2] 蒋雷 CAO Hui;YU Zheng;FAN Yichun;LIN Yuxin;WANG Jun;GAO Rong;JIANG Lei(Department of Hygienic Analysis and Detection,Nanjing Qixia District Center for Disease Control and Prevention,Nanjing 210046;Department of Hygienic Analysis and Detection,School of Public Health,Nanjing Medical University,Nanjing 211166;Department of Toxicology,School of Public Health,Nanjing Medical University,Nanjing 211166;Department of Emergency,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)

机构地区：[1]南京市栖霞区疾病预防控制中心检验科,江苏南京210046 [2]南京医科大学公共卫生学院卫生检验学系,江苏南京211166 [3]南京医科大学公共卫生学院卫生毒理学系,江苏南京211166 [4]南京医科大学第一附属医院急诊医学中心,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2023年第9期1194-1200,共7页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81701872)。

摘　　要：目的:探讨双酚F(bisphenol F,BPF)对肝脏中色氨酸(tryptophan,TRP)及酪氨酸(tyrosine,TYR)代谢的影响,阐明其代谢稳态扰乱后神经递质的代谢特点。方法:SPF级C57BL/6J小鼠经灌胃给予不同浓度的BPF[40、400、4000μg/(kg·d)],连续灌胃30 d,通过超高效液相色谱-串联质谱(ultra-high-performance liquid chromatography-tandem mass spectrometry,UHPLC-MS/MS)法观察BPF暴露后小鼠肝脏TRP、TYR来源神经递质代谢特点及水平的改变。结果:BPF暴露后引起小鼠肝脏TRP、TYR水平下降,其中TRP代谢途径的神经递质5-羟色胺(5-hydroxytryptamine,5-HT)水平明显下降,相反,犬尿氨酸(kynurenine,KYN)水平显著上升;TYR代谢途径中,TYR及其代谢产物多巴胺(dopamine,DA)水平显著下降;其他兴奋性神经递质如谷氨酸(glutamate,GLU)、γ-氨基丁酸(γ-aminobutyric acid,GABA)、天冬氨酸(aspartic acid,ASP)、甘氨酸(glycine,GLY)水平亦明显降低。结论:BPF暴露可抑制TRP、TYR及多个兴奋性神经递质的代谢,促进TRP通路中5-HT向KYN代谢转化,对肝脏神经递质代谢的探讨可为BPF持续暴露导致的肝脏及神经精神性病变提供依据。Objective:To investigate the effects of bisphenol F(BPF)on the tryptophan(TRP)and tyrosine(TYR)⁃derived neurotransmitter metabolism in the liver,elucidating the metabolic characteristics of the neurotransmitter disturbance elicited by BPF.Methods:The SPF C57BL/6J mice were administrated with different concentrations of BPF[40,400,4000μg/(kg·d)]by gavage for 30 consecutive days,and the ultra⁃high⁃performance liquid chromatography⁃tandem mass spectrometry(UHPLC⁃MS/MS)assay was used to examine the characteristics and levels of TRP and TYR⁃derived neurotransmitters in the mouse livers after BPF exposure.Results:The levels of TRP and TYR in mouse livers were significantly decreased after BPF exposure,and 5⁃hydroxytryptamine(5⁃HT)was significantly decreased,while kynurine(KYN),another key metabolite of the TRP metabolic pathway,significantly increased.For the TYR metabolism,TYR and its metabolite dopamine(DA)obviously decreased;meanwhile,other excitatory neurotransmitters,such as glutamate(GLU),γ⁃aminobutyric acid(GABA),aspartic acid(ASP)and glycine(GLY),dramatically decreased.Conclusion:BPF exposure can decrease the levels of TRP,TYR and several other excitatory neurotransmitters,and promote the metabolic transformation of 5⁃HT into KYN in the TRP pathway.Therefore,the current study on the metabolism of hepatic neurotransmitters provides novel evidence for the liver and neuropsychiatric diseases caused by continuous exposure to BPF.

关 键 词：双酚F 色氨酸 酪氨酸 神经递质代谢 肝脏 

分 类 号：R114[医药卫生—卫生毒理学]