中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (13): 1275-1282.doi: 10.4103/1673-5374.137574

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

积雪草苷的神经保护效应

  

  • 收稿日期:2014-05-17 出版日期:2014-07-11 发布日期:2014-07-11

Neuroprotective effects of Asiaticoside

Feng-yan Qi 1, Le Yang 1, Zhen Tian 1, Ming-gao Zhao 1, Shui-bing Liu 1, Jia-ze An 2   

  1. 1 Department of Pharmacology, School of Pharmacy, Fourth Military Medical University of Chinese PLA, Xi’an, Shaanxi Province, China
    2 Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University of Chinese PLA, Xi’an, Shaanxi Province, China
  • Received:2014-05-17 Online:2014-07-11 Published:2014-07-11
  • Contact: Jiaze An, Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University of Chinese PLA, Xi’an 710032, Shaanxi Province, China, anchen@fmmu.edu.cn. Shuibing Liu, Department of Pharmacology, School of Pharmacy, Fourth Military Medical University of Chinese PLA, Xi’an 710032, Shaanxi Province, China, liushb1974@aliyun.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 31271126, 81372606.

摘要:

以往体外研究发现积雪草苷可减轻β-淀粉样蛋白诱导的神经元损伤。然而,关于积雪草苷对谷氨酸诱导的兴奋性毒性的神经保护作用尚未见报道。为此,实验进行了这方面的观察,结果显示,积雪草苷剂量依赖性抑制N-甲基-D-天冬氨酸诱导神经元活力的降低,并可逆转N-甲基-D-天冬氨酸诱导凋亡蛋白Bcl-2和Bax的表达变化;能够显著逆转N-甲基-D-天冬氨酸受体NR2B亚基上调,但并不影响N-甲基-D-天冬氨酸受体NR2A亚基的表达;还能明显抑制N-甲基-D-天冬氨酸诱导的细胞内Ca2+超载。数据证明,积雪草苷通过抑制N-甲基-D-天冬氨酸引起的钙超载发挥神经保护作用。

关键词: 神经再生, 脑损伤, 积雪草苷, 细胞凋亡, 神经元, N-甲基-D-天冬氨酸, 谷氨酸, 神经递质, 神经毒性, 钙成像, Bcl-2, Bax, 国家自然科学基金

Abstract:

In the central nervous system, Asiaticoside has been shown to attenuate in vitro neuronal damage caused by exposure to β-amyloid. In vivo studies demonstrated that Asiaticoside could attenuate neurobehavioral, neurochemical and histological changes in transient focal middle cerebral artery occlusion animals. In addition, Asiaticoside showed anxiolytic effects in acute and chronic stress animals. However, its potential neuroprotective properties in glutamate-induced excitotoxicity have not been fully studied. We investigated the neuroprotective effects of Asiaticoside in primary cultured mouse cortical neurons exposed to glutamate-induced excitotoxicity invoked by N-methyl-D-aspartate. Pretreatment with Asiaticoside decreased neuronal cell loss in a concentration-dependent manner and restored changes in expression of apoptotic-related proteins Bcl-2 and Bax. Asiaticoside pretreatment also attenuated the upregulation of NR2B expression, a subunit of N-methyl-D-aspartate receptors, but did not affect expression of NR2A subunits. Additionally, in cultured neurons, Asiaticoside significantly inhibited Ca2+ influx induced by N-methyl-D-aspartate. These experimental findings provide preliminary evidence that during excitotoxicity induced by N-methyl-D-aspartate exposure in cultured cortical neurons, the neuroprotective effects of Asiaticoside are mediated through inhibition of calcium influx. Aside from its anti-oxidant activity, down-regulation of NR2B-containing N-methyl-D-aspartate receptors may be one of the underlying mechanisms in Asiaticoside neuroprotection.

Key words: nerve regeneration, brain injury, Asiaticoside, apoptosis, N-methyl-D-aspartate, glutamate, neurotransmitter, neurotoxicity, calcium imaging, Bcl-2, Bax, NSFC grant, neural regeneration

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