Page 204 - 《水产学报》2026年第01期

1 期 水 产 学 报 50 卷

Keap1 与 Nrf2 之间的相互作用被打断，使得 Nrf2 heme in the pathogenesis of severe sepsis[J]. Science Transla-
能够与抗氧化反应元件 (ARE) 结合，激活 Nrf2- tional Medicine, 2010, 2(51): 51ra71.
ARE 信号通路，从而激活下游的抗氧化基因，如 [ 7 ] Dev S, Babitt J L. Overview of iron metabolism in health and
gpx4、ho-1 等 [50-51] 。在本研究中，FAC 的孵育会 disease[J]. Hemodialysis International, 2017, 21(S1): S6-S20.
[ 8 ] Sukhbaatar N, Weichhart T. Iron regulation: macrophages in
导致 keap1、gpx4 和 ho-1 的 mRNA 水平显著上调，
control[J]. Pharmaceuticals, 2018, 11(4): 137.
细胞总 ROS 显著上升，说明铁过载导致了 L8824
[ 9 ] Ganz T . Macrophages and iron metabolism[J]. Microbiology
细胞抗氧化系统的失衡，诱导氧化应激。 SpectrumMicrobiol Spectr, 2016, 4(5): MCHD-0037-2016.
Zhao 等 [52] 研究发现，铁过载及 ROS 的增加 [10] Bayir H, Dixon S J, Tyurina Y Y, et al. Ferroptotic mechan-
可以通过 TLR4/P38-MAPK 通路激活炎症反应。 isms and therapeutic targeting of iron metabolism and lipid per-
在鲤铁死亡的研究中，脂质过氧化被发现能够激 oxidation in the kidney[J]. Nature Reviews Nephrology, 2023,
活 NF-κB/P65 信号通路，并导致炎症因子 TNF-α 19(5): 315-336.
[11] Lane D J R, Merlot A M, Huang M L M, et al. Cellular iron
的上调 。同时，还有研究指出，内质网应激的
[53]
uptake, trafficking and metabolism: key molecules and mechan-
主要信号通路 PERK-eIF2α 也能介导铁积累引起的
isms and their roles in disease[J]. Biochimica et Biophysica
铁死亡 [54-55] 。基于上述研究，本研究检测了这些
Acta (BBA) - Molecular Cell Research, 2015, 1853(5): 1130-
通路中的若干关键因子，发现 L8824 细胞经过 1144.
FAC 孵育 6 h 后，p65、tlr4、perk 和 p38-mapk 呈 [12] Yanatori I, Kishi F. DMT1 and iron transport[J]. Free Radical
下调趋势，tnf-α 则显著上调。在孵育 12 h 后，这 Biology and Medicine, 2019, 133: 55-63.
些基因的 mRNA 水平均显著上调，说明在铁离子 [13] Vogt A S, Arsiwala T, Mohsen M, et al. On iron metabolism
and its regulation[J]. International Journal of Molecular Sci-
积累到一定程度后，炎症相关通路将被激活。
ences, 2021, 22(9): 4591.
总之，本研究利用体外和体外实验证明了食
[14] Fraenkel P G, Traver D, Donovan A, et al. Ferroportin1 is
源性铁过载对草鱼肝脏健康的影响。结果表明，
required for normal iron cycling in zebrafish[J]. Journal of Clin-
铁过载可导致草鱼肝脏组织受损，破坏肝脏铁代 ical Investigation, 2005, 115(6): 1532-1541.
谢稳态，并诱导显著的氧化应激反应。此外，铁 [15] Sendamarai A K, Ohgami R S, Fleming M D, et al. Structure of
代谢紊乱进一步引起细胞内 ROS 水平升高，激活 the membrane proximal oxidoreductase domain of human
炎症反应通路。本研究为深入理解铁代谢紊乱对 Steap3, the dominant ferrireductase of the erythroid transferrin
cycle[J]. Proceedings of the National Academy of Sciences of
草鱼健康的潜在机制提供了理论依据，也为草鱼
the United States of America, 2008, 105(21): 7410-7415.
健康养殖管理策略的优化提供了重要参考。
[16] Zanninelli G, Loréal O, Brissot P, et al. The labile iron pool of
（作者声明本文无利益冲突） hepatocytes in chronic and acute iron overload and chelator-
induced iron deprivation[J]. Journal of Hepatology, 2002,
36(1): 39-46.
参考文献
[17] Ginzburg Y Z. Hepcidin-ferroportin axis in health and
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