[1]高丽娜,张璇,何俊芳.金雀异黄酮调节Nrf2/HO-1信号通路对海马神经元缺氧/复氧损伤的影响[J].卒中与神经疾病杂志,2024,(01):14-20.[doi:10.3969/j.issn.1007-0478.2024.01.003]
　Gao Lina,Zhang Xuan,He Junfang..Effect of Genistein on hypoxia/reoxygenation injury of hippocampal neurons by regulating Nrf2/HO-1 signaling pathway[J].Stroke and Nervous Diseases,2024,(01):14-20.[doi:10.3969/j.issn.1007-0478.2024.01.003]
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金雀异黄酮调节Nrf2/HO-1信号通路对海马神经元缺氧/复氧损伤的影响()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
期数:
2024年01期
页码:
14-20
栏目:
论著
出版日期:
2024-02-20

文章信息/Info

Title:
Effect of Genistein on hypoxia/reoxygenation injury of hippocampal neurons by regulating Nrf2/HO-1 signaling pathway
文章编号:
1007-0478(2024)01-0014-07
作者:
高丽娜; 张璇; 何俊芳
056000 河北省邯郸市中心医院神内四科
Author(s):
Gao Lina;  Zhang Xuan;  He Junfang.
Fourth Department of Neurology, Handan Central Hospital, Handan 056000
关键词:
金雀异黄酮; 海马神经元; 缺氧/复氧; 核因子E2相关因子2/血红素加氧酶1信号通路; 氧化应激; 凋亡
Keywords:
Genistein Hippocampal neurons Hypoxia/reoxygenation Nrf2/HO-1 signaling pathway Oxidative stress Apoptosis
分类号:
R285.5
DOI:
10.3969/j.issn.1007-0478.2024.01.003
文献标志码:
A
摘要:
目的 〖JP+2〗探讨金雀异黄酮（Genistein，Gen）调节核因子E2相关因子2/血红素加氧酶1（Nuclear factor E2 related factor 2/heme oxygenase-1，Nrf2/HO-1）信号通路对海马神经元缺氧/复氧（ Hypoxia/reoxygenation，H/R）损伤的影响。 方法 原代分离并体外培养SD（Sprague Dawley）大鼠胎鼠（妊娠18 d）海马神经元，设正常组、模型组、Gen（12.5 μmol/L）组、Gen（12.5 μmol/L）+Nrf2激动剂叔丁基对苯二酚（Tert butyl hydroquinone，TBHQ）（10 μmol/L）组和Gen（12.5 μmol/L）+Nrf2抑制剂（Nrf2 inhibitor，ML385）（10 μmol/L）组；采用缺氧4 h复氧24 h的方法构建海马神经元H/R损伤模型，各组均于造模前2 h给药；噻唑蓝四氮唑（Thiazolyl blue tetrazolium，MTT）法、膜联蛋白V-异硫氰酸荧光素/碘化丙啶（Annexin V-fluorescein isothiocyanate/propyl iodide，Annexin V-FITC/PI）双染法检测海马神经元活力和凋亡率，分光光度法检测活性氧（Reactive oxygen species，ROS）、丙二醛（Malondialdehyde，MDA）水平和超氧化物歧化酶（Superoxide dismutase，SOD）、过氧化氢酶（Catalase，CAT）活性，Western blot法检测海马神经元Nrf2/HO-1信号通路相关蛋白\[Nrf2，HO-1、B淋巴细胞瘤-2基因（B-cell lymphoma-2 gene，Bcl-2）、Bcl-2相关X蛋白（Bcl-2 associated X protein，Bax）、半胱氨酸蛋白酶-3（Cysteine proteinase-3，Caspase-3）、激活型Caspase-3（Cleaved Caspase-3）\]表达水平。 结果 与模型组比较，Gen组海马神经元活力显著升高、凋亡率显著降低（P<0.05）；ROS，MDA水平显著降低，SOD，CAT活性显著升高（P<0.05）；Nrf2，HO-1，Bcl-2表达水平显著升高，Bax，Cleaved Caspase-3表达水平及Bax/Bcl-2、Cleaved Caspase-3/Caspase-3比值显著降低（P<0.05）。TBHQ可明显增强Gen对H/R损伤海马神经元活力、凋亡率、氧化应激以及Nrf2/HO-1信号通路相关蛋白表达水平的调控作用；ML385则明显逆转Gen对H/R损伤海马神经元的上述调控作用。 结论 Gen对海马神经元H/R损伤具有保护作用，其机制可能与Gen上调Nrf2/HO-1信号通路，进而抑制氧化应激和神经元凋亡有关。
Abstract:
Objective〖WTBZ〗 To investigate the effect Genistein (Gen) on hypoxia/reoxygenation (H/R) injury of hippocampal neurons and its potential mechanism based on the nuclear factor E2 related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway. 〖WTHZ〗Methods 〖WTBZ〗 The primary hippocampal neurons of SD (Sprague Dawley) fetal rats (18 d gestation) were isolated and cultured in vitro, and the normal group, model group, Gen (12.5 μmol/L) group, Gen (12.5 μmol/L)+Nrf2 agonis tert butyl hydroquinone (TBHQ) (10 μmol/L) group, Gen (12.5 μmol/L)+Nrf2 inhibitor ML385 (10 μmol/L) group were set up. The H/R injury model of hippocampal neurons was established by hypoxia for 4 h and reoxygenation for 24 h. 2 h before modeling, the hippocampal neurons in each group were intervened. The viability and apoptosis rate of hippocampal neurons were detected by thiazolyl blue tetrazolium (MTT) or Annexin V-fluorescein isothiocyanate/propyl iodide (Annexin V-FITC/PI) double dyeing. The content of reactive oxygen species (ROS), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), catalase (CAT) were detected by spectrophotometry. The related protein expression of Nrf2/HO-1 signaling pathway \[Nrf2, HO-1, B-lymphoblastoma-2 gene (Bcl-2), Bcl-2 associated X protein (Bax), Cysteine proteinase-3 (Caspase-3), Cleaved Caspase-3\] were detected by Western blot. 〖WTHZ〗Results 〖WTBZ〗 Compared with the model group, the viability of hippocampal neurons in Gen group was significantly increased, while the apoptosis rate was significantly decreased (P<0.05). The content of ROS, MDA were significantly decreased and the activity of SOD, CAT was significantly increased (P<0.05). The expression of Nrf2, HO-1, Bcl-2 were significantly increased, the expression of Bax, Cleaved Caspase-3 and the ratio of Bax/Bcl-2, Cleaved Caspase-3/Caspase-3 were significantly decreased (P<0.05). TBHQ could significantly enhance the regulatory effects of Gen on the viability, apoptosis rate, oxidative stress and Nrf2/HO-1 signaling pathway related protein expression of H/R damaged hippocampal neurons. ML385 significantly reversed the regulatory effects of Gen on H/R damaged hippocampal neurons. 〖WTHZ〗Conclusion 〖WTBZ〗 Gen has protective effect on H/R injury of hippocampal neurons through the up-regulation of Nrf2/HO-1 signaling pathway and inhibition of oxidative stress and neuronal apoptosis.

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相似文献/References:

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备注/Memo

备注/Memo:
基金项目：河北省医学科学研究课题（编号为20220017）
更新日期/Last Update: 2024-02-20