中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (4): 654-659.doi: 10.4103/1673-5374.205107

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

开心散保护神经元的证据：上调海马区IDE蛋白表达并促进Aβ降解

  

  • 收稿日期:2017-02-25 出版日期:2017-04-15 发布日期:2017-04-15
  • 基金资助:

    国家自然科学基金（81303248，81603321）；黑龙江省自然科学基金(H2015028)；黑龙江省青年学者资助项目（UNPYSCT-2016116）；齐齐哈尔医学院科研基金（QY2016B-09）

Neuroprotective mechanism of Kai Xin San: upregulation of hippocampal insulin-degrading enzyme protein expression and acceleration of amyloid-beta degradation

Na Wang1, Yong-ming Jia1, Bo Zhang2, Di Xue1, Maharjan Reeju1, Yan Li2, Shu-ming Huang2, Xue-wei Liu1   

  1. 1 Institute of Medicine, Qiqihar Medical University, Qiqihar, Heilongjiang Province, China; 2 Department of Neuroscience, Institute of Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China
  • Received:2017-02-25 Online:2017-04-15 Published:2017-04-15
  • Contact: Xue-wei Liu, Ph.D., lxw_qmu@126.com.
  • Supported by:

    This research was supported by the National Natural Science Foundation of China, No. 81303248, 81603321; the Natural Science Foundation of Heilongjiang Province of China, No. H2015028; a grant from the Nursing Program for Young Scholars of Heilongjiang Province of China, No. UNPYSCT-2016116; the Scientific Research Fund for Doctors of Qiqihar Medical University in China, No. QY2016B-09.

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摘要：

开心散是由人参、远志、石菖蒲和茯苓组成的一个传统中药复方，常用于治疗健忘症。研究发现，开心散能够保护神经元及减轻β-淀粉样蛋白(Aβ)诱导的认知功能障碍，但具体机制不明。胰岛素降解酶(IDE)为最关键的β淀粉样蛋白降解酶，与认知功能的调节密切相关。实验在大鼠双侧海马CA1区分别注射外源性Aβ42 (200 μM) 5 μL，连续21 d灌胃开心散（0.54，1.08 g/kg/d），通过苏木精伊红染色和尼氏染色发现大鼠脑组织Aβ42注射引起的神经元的损伤显著减轻。通过ELISA，Western blot，PCR检测发现，开心散（0.54，1.08 g/kg/d）能够降低大鼠脑组织Aβ42蛋白水平，海马区IDE蛋白表达明显增加，但IDE的基因表达无显著改变。结果证实，开心散能够上调海马区IDE蛋白表达，在一定程度上促进Aβ降解，可能以此发挥神经元保护作用。

ORCID:0000-0002-0381-7548(Xue-wei Liu)

关键词: 神经再生, 神经退行性变, 中医药, 开心散, 胰岛素降解酶, β-淀粉样蛋白, 阿尔茨海默病, 中药复方, β-淀粉样蛋白降解酶, 神经元, 人参, 远志, 石菖蒲

Abstract:

Kai Xin San is a Chinese herbal formula composed of Radix Ginseng, Poria, Radix Polygalae and Acorus Tatarinowii Rhizome. It has been used in China for many years for treating amnesia. Kai Xin San ameliorates amyloid-β (Aβ)-induced cognitive dysfunction and is neuroprotective in vivo, but its precise mechanism remains unclear. Expression of insulin-degrading enzyme (IDE), which degrades Aβ, is strongly correlated with cognitive function. Here, we injected rats with exogenous Aβ42 (200 μM, 5 μL) into the hippocampus and subsequently administered Kai Xin San (0.54 or 1.08 g/kg/d) intragastrically for 21 consecutive days. Hematoxylin-eosin and Nissl staining revealed that Kai Xin San protected neurons against Aβ-induced damage. Furthermore, enzyme-linked immunosorbent assay, western blot and polymerase chain reaction results showed that Kai Xin San decreased Aβ42 protein levels and increased expression of IDE protein, but not mRNA, in the hippocampus. Our findings reveal that Kai Xin San facilitates hippocampal Aβ degradation and increases IDE expression, which leads, at least in part, to the alleviation of hippocampal neuron injury in rats.

Key words: nerve regeneration, neurodegeneration, traditional Chinese medicine, Kai Xin San, insulin-degrading enzyme, amyloid-β, Alzheimer’s disease, Chinese herbal compound, Aβ-degrading enzymes, neurons, Radix Ginseng, Radix Polygalae, Acorus Tatarinowii Rhizoma, neural regeneration