中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (6): 924-930.doi: 10.4103/1673-5374.184490

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

短暂性脑缺血后12h应关注海马铁过载?

  

  • 收稿日期:2016-04-28 出版日期:2016-06-30 发布日期:2016-06-30
  • 基金资助:

    韩国教育部基础科学研究项目;首尔国立大学兽医科学研究所基金

Time- and cell-type specific changes in iron, ferritin, and transferrin in the gerbil hippocampal CA1 region after transient forebrain ischemia

Dae Young Yoo1, Ki-Yeon Yoo2, Joon Ha Park3, Hyun Jung Kwon4, Hyo Young Jung1, Jong Whi Kim1, Goang-Min Choi5, Seung Myung Moon6, Dae Won Kim4, Yeo Sung Yoon1, Moo-Ho Won3, In Koo Hwang1, *   

  1. 1 Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, South Korea 2 Department of Oral Anatomy, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, South Korea 3 Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, South Korea 4 Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung, South Korea 5 Department of Thoracic and Cardiovascular Surgery, Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University, Chuncheon, South Korea 6 Department of Neurosurgery, Dongtan Sacred Heart Hospital, College of Medicine, Hallym University, Hwaseong, South Korea
  • Received:2016-04-28 Online:2016-06-30 Published:2016-06-30
  • Contact: In Koo Hwang, D.V.M., Ph.D., vetmed2@snu.ac.kr.
  • Supported by:

    This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, No. 2015R1D1A1A01059980. This study was also partially supported by the Research Institute for Veterinary Science, Seoul National University.

摘要:

铁在髓鞘形成、神经递质合成与代谢、以及神经元树突发育中起重要作用,其过载会产生氧自由基,从而损害神经元。已有研究应用生化手段检测脑缺血后铁、铁蛋白和转铁蛋白的变化,但尚未见3者在短暂性脑缺血状态下细胞水平变化相关报道。实验应用免疫组化和免疫印迹检测沙土鼠短暂性前脑缺血后30min至7d海马CA1区铁、铁蛋白重链、转铁蛋白水平和细胞定位的变化。(1)相对于假手术对照组,海马CA1区锥体细胞层和多形细胞层在缺血后12h铁反应明显上升,然后在1-2d时出现短暂下降,于缺血后4-7d在CA1区再次上升;(2)缺血后1d海马CA1区锥体细胞层铁蛋白重链免疫反应明显增强;缺血后2d则减弱;缺血后4-7d海马CA1区胶质细胞中铁蛋白重链免疫反应明显增强;(3)海马CA1区锥体细胞层转铁蛋白免疫反应在缺血后12h明显增强,1d时达到峰值,2d时明显减弱;缺血后7d,海马CA1区胶质细胞检测到转铁蛋白免疫反应在多形细胞层和辐射层明显增强。铁蛋白重链、转铁蛋白的免疫印迹结果支持前述免疫组化染色结果。说明海马CA1区锥体细胞层在短暂性脑缺血后12h铁过载最为明显,此时可能是保护脑缺血后铁过载诱导神经元死亡的最佳时间。脑缺血后海马短暂的铁蛋白和转铁蛋白水平的上升可能是为了代偿铁超载。

orcid: 0000-0002-0533-4638 (In koo Hwang)

关键词: 神经再生, 脑缺血, 铁, 铁蛋白重链, 转铁蛋白, CA1区, 氧化应激

Abstract:

In the present study, we used immunohistochemistry and western blot analysis to examine changes in the levels and cellular localization of iron, heavy chain ferritin (ferritin-H), and transferrin in the gerbil hippocampal CA1 region from 30 minutes to 7 days following transient forebrain ischemia. Relative to sham controls, iron reactivity increased significantly in the stratum pyramidale and stratum oriens at 12 hours following ischemic insult, transiently decreased at 1–2 days and then increased once again within the CA1 region at 4–7 days after ischemia. One day after ischemia, ferritin-H immunoreactivity increased significantly in the stratum pyramidale and decreased at 2 days. At 4–7 days after ischemia, ferritin-H immunoreactivity in the glial components in the CA1 region was significantly increased. Transferrin immunoreactivity was increased significantly in the stratum pyramidale at 12 hours, peaked at 1 day, and then decreased significantly at 2 days after ischemia. Seven days after ischemia, Transferrin immunoreactivity in the glial cells of the stratum oriens and radiatum was significantly increased. Western blot analyses supported these results, demonstrating that compared to sham controls, ferritin H and transferrin protein levels in hippocampal homogenates significantly increased at 1 day after ischemia, peaked at 4 days and then decreased. These results suggest that iron overload-induced oxidative stress is most prominent at 12 hours after ischemia in the stratum pyramidale, suggesting that this time window may be the optimal period for therapeutic intervention to protect neurons from ischemia-induced death.

Key words: nerve regeneration, ischemia, iron, ferritin heavy chain, transferrin, CA1 region, oxidative stress, neural regeneration