双酚F暴露后对小鼠肝脏神经递质代谢的影响
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国家自然科学基金(81701872)


Bisphenol F exposure disrupts metabolism of neurotransmitters in mouse liver
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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。

    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.

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曹辉,余正,范一纯,林雨欣,王军,高蓉,蒋雷.双酚F暴露后对小鼠肝脏神经递质代谢的影响[J].南京医科大学学报(自然科学版),2023,(9):1194-1200

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  • 收稿日期:2023-03-29
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  • 在线发布日期: 2023-09-16
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