中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (3): 481-489.doi: 10.4103/1673-5374.153700

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

姜黄素预处理或后处理均可提高氧糖剥夺神经元的抗氧化能力

  

  • 收稿日期:2014-10-23 出版日期:2015-03-20 发布日期:2015-03-20
  • 基金资助:

    国家自然科学基金（81171090），重庆教育委员会自然科学基金（kj110313），复旦大学的神经生物学国家重点实验室基金（10-08），第三军医大学教育部重点实验室基金

Curcumin pretreatment and post-treatment both improve the antioxidative ability of neurons with oxygen-glucose deprivation

Jing-xian Wu 1, 2, Lu-yu Zhang 3, Yan-lin Chen 1, 2, Shan-shan Yu 1, 2, Yong Zhao 1, 2, Jing Zhao 2, 4   

  1. 1 Department of Pathology, Chongqing Medical University, Chongqing, China
    2 Institute of Neuroscience, Chongqing Medical University, Chongqing, China
    3 Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China
    4 Department of Pathophysiology, Chongqing Medical University, Chongqing, China
  • Received:2014-10-23 Online:2015-03-20 Published:2015-03-20
  • Contact: Jing Zhao, M.D., yangyang741022@sina.com
  • Supported by:

    This study was supported by grants from the National Natural Science Foundation of China, No. 81171090; Natural Science Foundation of Chongqing Education Committee of China, No. KJ110313; Foundation of Key State Laboratory of Neurobiology of Fudan University in China, No. 10-08; and Foundation of Key Laboratory of Ministry of Education of the Third Medical Military University in China

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摘要：

最近研究显示，活化ARE/Nrf2信号通路，诱导内源性抗氧化酶可能是脑神经保护治疗的新策略。鉴于此，实验采用姜黄素10μmol/L预处理或5 μmol/L后处理体外培养的大鼠大脑皮质神经元，在氧糖剥夺复氧后24 h时进行观察。PI/Hoechst染色显示，两种处理方法均可减少神经元的损伤。Western blot显示经姜黄素预/后处理的神经元内Nrf2蛋白表达增加，姜黄素也可增加缺氧前/缺氧后/复氧后神经元内Trx蛋白表达和酶活性，两种处理方式无显著差异。此外，免疫细胞学染色显示姜黄素后处理可减轻复氧时神经元DNA/RNA氧化，并且通过诱导Nrf2核聚集来增加胞核内Nrf2的表达。结果提示，姜黄素可活化Nrf2通路上的抗氧化基因Trx的表达，并在缺血再灌注体外模型中保护神经元免受氧糖剥夺损伤，这表明姜黄素刺激抗氧化基因表达可能是脑缺血后神经保护治疗的潜力方法。

关键词: 神经再生, 脑损伤, 姜黄素, 缺血再灌注损伤, 氧化应激, 原代培养细胞, 皮质神经元, 氧糖剥夺, 抗氧化通路；预处理, 后处理, 国家自然科学基金

Abstract:

Recent studies have shown that induced expression of endogenous antioxidative enzymes thr-ough activation of the antioxidant response element/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway may be a neuroprotective strategy. In this study, rat cerebral cortical neurons cultured in vitro were pretreated with 10 μM curcumin or post-treated with 5 μM curcumin, respectively before or after being subjected to oxygen-glucose deprivation and reoxygenation for 24 hours. Both pretreatment and post-treatment resulted in a significant decrease of cell injury as indicated by propidium iodide/Hoechst 33258 staining, a prominent increase of Nrf2 protein expression as indicated by western blot analysis, and a remarkable increase of protein expression and enzyme activity in whole cell lysates of thioredoxin before ischemia, after ischemia, and after reoxygenation. In addition, post-treatment with curcumin inhibited early DNA/RNA oxidation as indicated by immunocytochemistry and increased nuclear Nrf2 protein by inducing nuclear accumulation of Nrf2. These findings suggest that curcumin activates the expression of thioredoxin, an antioxidant protein in the Nrf2 pathway, and protects neurons from death caused by oxygen-glucose deprivation in an in vitro model of ischemia/reperfusion. We speculate that pharmacologic stimulation of antioxidant gene expression may be a promising approach to neuroprotection after cerebral ischemia.

Key words: nerve regeneration, brain injury, curcumin, ischemia/reperfusion injury, oxidative stress, primary cell culture, cortical neurons, oxygen-glucose deprivationv pretreatment, post-treatment, NSFC grant, neural regeneration