中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (12): 1071-1080.doi: 10.3969/j.issn.1673-5374.2013.12.002

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

木犀草素减少糖尿病脑病大鼠海马神经细胞的凋亡

  

  • 收稿日期:2012-12-03 修回日期:2013-03-21 出版日期:2013-04-25 发布日期:2013-04-25

Luteolin attenuates neuronal apoptosis in the hippocampi of diabetic encephalopathy rats

Guiru Ren, Jingjing Kong, Ning Jia, Xiuli Shang   

  1. Department of Neurology, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
  • Received:2012-12-03 Revised:2013-03-21 Online:2013-04-25 Published:2013-04-25
  • Contact: Xiuli Shang, Doctoral supervisor, Department of Neurology, the First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China, shang_zhao@sohu.com.
  • About author:Guiru Ren☆, Studying for doctorate, Associate chief physician.

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摘要：

木犀草素具有强大的抗细胞凋亡及抗氧化作用。实验以此观察尾静脉注射木犀草素对链脲佐菌素诱导的糖尿病脑病大鼠海马神经细胞凋亡的影响及其分子机制。生化指标及TUNEL检测结果显示，木犀草素可降低糖尿病脑病大鼠海马组织丙二醛水平，提高谷胱甘肽水平，明显抑制糖尿病脑病大鼠海马细胞凋亡。Western blot结果显示，木犀草素在减少糖尿病脑病大鼠海马细胞色素C从线粒体的释放的同时，抑制凋亡相关因子的表达。水迷宫实验检测显示，木犀草素可改善糖尿病脑病大鼠的学习记忆能力。由于PI3K/Akt为凋亡相关的细胞外信号通路，可在抑制细胞凋亡，促进细胞存活中发挥重要作用。因此，进一步的western blot检测结果显示，木犀草素可激活糖尿病脑病大鼠海马PI3K/Akt信号通路。实验证实，木犀草素能够抑制糖尿病脑病大鼠的海马神经细胞凋亡，其机制是通过间接的抗氧化作用、抑制凋亡相关因子激活及促进PI3K/Akt信号通路的激活实现。

关键词:

 

Abstract:

Luteolin (3’,4’,5,7-tetrahydroxyflavone) has powerful anti-apoptotic and antioxidant properties. This study aimed to investigate the effects of luteolin on hyperglycemia-mediated apoptosis in the hippocampi of rats with streptozotocin-induced diabetic encephalopathy after injection into the tail veins, and the molecular mechanisms involved. Biochemistry and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling detection results showed that luteolin treatment (given twice daily for 15 days) significantly inhibited hyperglycemia-mediated apoptosis, decreased malondialdehyde levels and increased glutathione levels in the hippocampi of streptozotocin- induced diabetic rats. Western blot analysis revealed that luteolin also inhibited the expression of apoptosis-related factors and cytochrome c release from mitochondria. Luteolin also improved the learning and memory abilities of rats with diabetic encephalopathy in a water maze test. Further western blot analysis revealed that luteolin treatment facilitated neuronal cell survival through activation of the phosphatidylinositol 3-kinase/Akt signaling pathway, an extracellular signal pathway involved in the suppression of cell apoptosis and promotion of cell survival. These experimental findings indicate that luteolin can inhibit apoptosis of hippocampal nerve cells in rats with diabetic encephalopathy, and that this effect is mediated by an indirect antioxidative effect, the inhibition of activation of apoptosis-related factors and the activation of phosphatidylinositol 3-kinase/Akt signal pathway.

Key words: neural regeneration, brain injury, diabetic mellitus, luteolin, apoptosis, learning and memory, spatial recognition memory, nerve cells, hippocampus, anti-oxidation, neuroregeneration