Page 16 - 南京医科大学学报自然科学版

南京医科大学学报（自然科学版） 第43卷第9期
·1194 · Journal of Nanjing Medical University（Natural Sciences） 2023年9月

·基础研究·

双酚F暴露后对小鼠肝脏神经递质代谢的影响

曹 辉 ，余 正 ，范一纯 ，林雨欣 ，王 军 ，高 蓉 ，蒋 雷 4*
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南京市栖霞区疾病预防控制中心检验科，江苏 南京 210046；南京医科大学公共卫生学院卫生检验学系，卫生毒理学系，
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江苏 南京 211166；南京医科大学第一附属医院急诊医学中心，江苏 南京 210029
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［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、4 000 μg/（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。
［关键词］ 双酚F；色氨酸；酪氨酸；神经递质代谢；肝脏
［中图分类号］ R114 ［文献标志码］ A ［文章编号］ 1007⁃4368（2023）09⁃1194⁃07
doi：10.7655/NYDXBNS20230902

Bisphenol F exposure disrupts metabolism of neurotransmitters in mouse liver

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CAO Hui ，YU Zheng ，FAN Yichun ，LIN Yuxin ，WANG Jun ，GAO Rong ，JIANG Lei 4*
1 Department of Hygienic Analysis and Detection，Nanjing Qixia District Center for Disease Control and Prevention，
Nanjing 210046；Department of Hygienic Analysis and Detection，Department of Toxicology，School of Public
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Health，Nanjing Medical University，Nanjing 211166；Department of Emergency，the First Affiliated Hospital of
Nanjing Medical University，Nanjing 210029，China
［Abstract］ 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［40，400，4 000 μg/（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.
［Key words］ bisphenol F；tryptophan；tyrosine；neurotransmitter metabolism；liver
［J Nanjing Med Univ，2023，43（09）：1194⁃1200］

［基金项目］ 国家自然科学基金（81701872）
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通信作者（Corresponding author），E⁃mail：racheljl@126.com