[暴露于高海拔缺氧环境的小鼠海马中与铁氧化相关通路的变化]

Q3 Medicine
生理学报 Pub Date : 2024-08-25
Xi-Wen Chang, An-Peng Zhao, Yan Zhong, Fei-Fei Liu, Rong Wang
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引用次数: 0

摘要

本研究旨在探讨小鼠海马组织在暴露于高海拔缺氧环境后发生的铁突变及相关通路的变化。采用 HE 染色观察小鼠海马组织的形态学变化,采用免疫组化染色观察海马组织的脂质过氧化水平,采用相应的试剂盒检测海马组织中丙二醛(MDA)、还原型谷胱甘肽(GSH)和 Fe2+ 的水平。用 Western 印迹法检测谷胱甘肽过氧化物酶 4(GPX4)、溶质运载体家族 7 成员 11(SLC7A11)、铁蛋白重链 1(FTH1)、铁蛋白 1(FPN1)、转铁蛋白受体 1(TfR1)、铁突变抑制蛋白 1(FSP1)和酰基-CoA 合成酶长链家族成员 4(ACSL4)。结果表明,与普通对照组相比,暴露于高海拔缺氧环境 1、3、7 和 14 d 的小鼠海马齿状回出现了明显的病理损伤、排列紊乱和明显的核凝缩。与普通对照组相比,高海拔缺氧增加了海马齿状回中4-羟基壬烯醛(4-HNE)的含量和海马MDA的含量,同时显著降低了海马GSH的含量。与普通对照组相比,暴露于高海拔缺氧环境 14 d 的小鼠海马中的 Fe2+ 含量明显增加。与普通对照组相比,暴露于高海拔缺氧环境的小鼠海马中 GPX4、FTH1、FPN1、TfR1 和 FSP1 的蛋白表达水平明显下调(SLC7A11 仅在暴露于高海拔缺氧环境 7 天的组别中明显下调),而 ACSL4 的蛋白表达水平仅在暴露于高海拔缺氧环境 14 天的组别中明显上调。这些结果表明,暴露于高海拔缺氧环境14 d可减少小鼠海马GSH的合成,下调GPX4的表达,导致GSH代谢紊乱,抑制铁的储存和外流,促进脂质过氧化反应,抑制CoQ10H2的抗脂质过氧化作用,最终导致铁变态反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Changes of ferroptosis related pathways in hippocampus of mice exposed to high-altitude hypoxia].

The present study aimed to investigate the occurrence of ferroptosis in mouse hippocampal tissue and changes in related pathways after exposure to high-altitude hypoxia. A low-pressure hypoxia model was established using a high-altitude environment at 4 010 m. HE staining was used to observe morphological changes in mouse hippocampal tissue, immunohistochemical staining was used to observe lipid peroxidation levels in hippocampal tissue, and corresponding kits were used to measure malondialdehyde (MDA), reduced glutathione (GSH), and Fe2+ levels in hippocampal tissue. Western blot was used to detect glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), ferritin heavy chain 1 (FTH1), ferroportin 1 (FPN1), transferrin receptor 1 (TfR1), ferroptosis suppressor protein 1 (FSP1), and acyl-CoA synthase long chain family member 4 (ACSL4). The results showed that, compared with the plain control group, the mice exposed to high-altitude hypoxia for 1, 3, 7, and 14 d exhibited significant pathological damage, disordered arrangement, and obvious nuclear condensation in the dentate gyrus of the hippocampus. Compared with the plain control group, high-altitude hypoxia exposure increased 4-hydroxynonenal (4-HNE) content in the dentate gyrus and hippocampal MDA content, whereas significantly decreased hippocampal GSH content. Compared with the plain control group, the Fe2+ content in the hippocampus of mice exposed to high-altitude hypoxia for 14 d significantly increased. Compared with the plain control group, the protein expression levels of GPX4, FTH1, FPN1, TfR1, and FSP1 in the hippocampus of mice exposed to high-altitude hypoxia were significantly down-regulated (SLC7A11 was significantly down-regulated only in the 7-d high-altitude hypoxia exposure group), while the protein expression level of ACSL4 was only significantly up-regulated in the 14-d high-altitude hypoxia exposure group. These results suggest that exposure to high-altitude hypoxia for 14 d can reduce GSH synthesis in mouse hippocampus, down-regulate GPX4 expression, lead to GSH metabolism disorders, inhibit iron storage and efflux, promote lipid peroxidation reaction, and inhibit CoQ10H2's anti-lipid peroxidation effect, ultimately leading to ferroptosis.

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来源期刊
生理学报
生理学报 Medicine-Medicine (all)
CiteScore
1.20
自引率
0.00%
发文量
4820
期刊介绍: Acta Physiologica Sinica (APS) is sponsored by the Chinese Association for Physiological Sciences and Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences (CAS), and is published bimonthly by the Science Press, China. APS publishes original research articles in the field of physiology as well as research contributions from other biomedical disciplines and proceedings of conferences and symposia of physiological sciences. Besides “Original Research Articles”, the journal also provides columns as “Brief Review”, “Rapid Communication”, “Experimental Technique”, and “Letter to the Editor”. Articles are published in either Chinese or English according to authors’ submission.
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