氟暴露诱导 SD 大鼠原代星形胶质细胞氧化损伤及 α-突触核蛋白表达变化及其对 Nrf2-NQO1/HO-1 信号通路的影响
Fluoride exposure induces oxidative damage in primary astrocytes of SD rats and changes in the expression of α-synuclein and its effect on Nrf2-NQO1/HO-1 signaling pathway.
摘要(中文译文)
长期过量摄入氟化物会在脑组织中蓄积，引起神经元变性和神经系统功能障碍。其机制与氧化应激升高密切相关。α-突触核蛋白（α-Syn）表达于神经元突触前终末，在环境毒素暴露或氧化应激条件下，其表达发生变化并错误折叠为具有细胞毒性的寡聚体和聚集体，诱导氧化性细胞损伤。同时，核因子E2相关因子2（Nrf2）-NAD(P)H：醌氧化还原酶1（NQO1）/血红素加氧酶-1（HO-1）通路是调节氧化损伤的重要细胞系统，其核心激酶主要表达于脑星形胶质细胞。本研究旨在探讨氟暴露对星形胶质细胞氧化应激水平的影响以及Nrf2-NQO1/HO-1通路内α-Syn的表达。原代星形胶质细胞经细胞外α-突触核蛋白预成纤维（αSP）处理并联合氟暴露。结果表明，氟暴露诱导原代星形胶质细胞反应性活化，活性氧（ROS）水平升高，超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性降低，并上调Nrf2-NQO1/HO-1通路的蛋白表达。αSP引起原代星形胶质细胞氧化应激，并加剧氟暴露诱导的氧化损伤。这些发现对于加深理解慢性氟中毒相关脑损伤的机制具有重要意义。
Abstract
Long-term excessive fluoride intake accumulates in brain tissue, causing neuronal degeneration and nervous system dysfunction. This mechanism is closely related to elevated oxidative stress. α-Synuclein (α-Syn) is expressed in neuronal presynaptic terminals; under environmental toxin exposure or oxidative stress, its expression changes and it misfolds into oligomers and aggregates that are cytotoxic and induce oxidative cellular damage. Meanwhile, the nuclear factor erythroid 2-related factor 2 (Nrf2)-NAD(P)H: quinone oxidoreductase 1 (NQO1)/heme oxygenase-1 (HO-1) pathway is an important cellular system for regulating oxidative damage, and its core kinase is mainly expressed in brain astrocytes.The aim of this study is to investigate the effects of fluoride exposure on oxidative stress levels in astrocytes and the expression of α-Syn within the Nrf2-NQO1/HO-1 pathway. Primary astrocytes were treated with extracellular α-synuclein pre-formed fibrils (αSP) in conjunction with fluoride exposure. The results demonstrated that fluoride exposure induced reactive activation of primary astrocytes, increased levels of reactive oxygen species (ROS), decreased activities of superoxide dismutase (SOD) and catalase (CAT), and up-regulated the protein expression within the Nrf2-NQO1/HO-1 pathway. αSP caused oxidative stress in primary astrocytes and exacerbated oxidative damage induced by fluoride exposure. These findings are significant for enhancing the understanding of the mechanisms underlying brain injury associated with chronic fluorosis.
如何引用
AMA
Xiao Zhou, Kaiju Mo, Wen Wan, Ling Ye, Minghai Liu, Zhizhong Guan, et al. Fluoride exposure induces oxidative damage in primary astrocytes of SD rats and changes in the expression of α-synuclein and its effect on Nrf2-NQO1/HO-1 signaling pathway.. Journal of bioenergetics and biomembranes. 2026; doi:10.1007/s10863-026-10128-8.
APA
Xiao Zhou, Kaiju Mo, Wen Wan, Ling Ye, Minghai Liu, Zhizhong Guan, et al (2026). Fluoride exposure induces oxidative damage in primary astrocytes of SD rats and changes in the expression of α-synuclein and its effect on Nrf2-NQO1/HO-1 signaling pathway.. Journal of bioenergetics and biomembranes. https://doi.org/10.1007/s10863-026-10128-8
GB/T 7714
Xiao Zhou, Kaiju Mo, Wen Wan, Ling Ye, Minghai Liu, Zhizhong Guan, et al. Fluoride exposure induces oxidative damage in primary astrocytes of SD rats and changes in the expression of α-synuclein and its effect on Nrf2-NQO1/HO-1 signaling pathway.[J]. Journal of bioenergetics and biomembranes, 2026 doi:10.1007/s10863-026-10128-8.
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