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 (10): 1680-1686.doi: 10.4103/1673-5374.217347

• 原著:退行性病与再生 • 上一篇    下一篇

中药复方补肾填髓汤对阿尔茨海默病海马突触的保护

  

  • 收稿日期:2017-08-20 出版日期:2017-10-15 发布日期:2017-10-15
  • 基金资助:

    国家自然科学基金（81373705）; 湖南省自然科学基金（13JJ3030）

Protective effects of Bushen Tiansui decoction on hippocampal synapses in a rat model of Alzheimer’s disease

Shan Hui1, 2, Yu Yang2, Wei-jun Peng1, Chen-xia Sheng1, Wei Gong1, Shuai Chen1, Pan-pan Xu1, Zhe Wang1   

  1. 1 Department of Integrated Chinese and Western Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
    2 Department of Geriatric Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
  • Received:2017-08-20 Online:2017-10-15 Published:2017-10-15
  • Contact: Zhe Wang, M.D.,ericwangzhe@csu.edu.cn.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81373705; the Natural Science Foundation of Hunan Province in China, No. 13JJ3030.

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摘要：

已有研究证实，由淫羊藿、何首乌、龟板、龙骨、远志、石菖蒲组成的中药复方补肾填髓汤，能有效对抗阿尔茨海默病β-淀粉样蛋白的毒性。我们假设补肾填髓汤是通过减轻海马突触损害而改善阿尔茨海默病的认知功能。实验方案为向大鼠双侧侧脑室微量注射Aβ25-35聚合物建立阿尔茨海默病模型，然后灌胃补肾填髓汤（0.563，1.688，3.375 g/mL，4mL/d）28 d发现灌胃补肾填髓汤能够阻止模型大鼠海马突触丢失，上调对海马突触可塑性有调节作用的Shank1，N-甲基-D-天门冬氨酸受体2B亚基及突触后致密物质95蛋白的表达；Morris水迷宫检测显示，此时阿尔茨海默病大鼠可缩短水迷宫潜伏期，增加穿越平台次数及目标象限时间百分比。结果证实补肾填髓汤上调了阿尔茨海默病大鼠海马突触相关蛋白Shank1，N-甲基-D-天门冬氨酸受体2B亚基及突触后致密物质95的表达，起到保护突触的作用。

orcid:0000-0002-1118-9721(Zhe Wang)

关键词: 神经再生, 神经退行性变, 补肾填髓方, 阿尔茨海默病, 突触可塑性, &beta, -淀粉样蛋白, 突触蛋白, Shank1 , N-甲基-D-天门冬氨酸受体2B亚基, 突触后致密物质95 , 水迷宫

Abstract:

Bushen Tiansui decoction is composed of six traditional Chinese medicines: Herba Epimedii, Radix Polygoni multiflori, Plastrum testudinis,Fossilia Ossis Mastodi, Radix Polygalae, and Rhizoma Acorus tatarinowii. Because Bushen Tiansui decoction is effective against amyloid beta (Aβ) toxicity, we hypothesized that it would reduce hippocampal synaptic damage and improve cognitive function in Alzheimer’s disease. To test this hypothesis, we used a previously established animal model of Alzheimer’s disease, that is, microinjection of aggregated Aβ25–35 into the bilateral brain ventricles of Sprague-Dawley rats. We found that long-term (28 days) oral administration of Bushen Tiansui decoction (0.563, 1.688, and 3.375 g/mL; 4 mL/day) prevented synaptic loss in the hippocampus and increased the expression levels of synaptic proteins, including postsynaptic density protein 95, the N-methyl-D-aspartate receptor 2B subunit, and Shank1. These results suggested that Bushen Tiansui decoction can protect synapses by maintaining the expression of these synaptic proteins. Bushen Tiansui decoction also ameliorated measures reflecting spatial learning and memory deficits that were observed in the Morris water maze (i.e., increased the number of platform crossings and the amount of time spent in the target quadrant and decreased escape latency) following intraventricular injections of aggregated Aβ25–35 compared with those measures in untreated Aβ25–35-injected rats. Overall, these results provided evidence that further studies on the prevention and treatment of dementia with this traditional Chinese medicine are warranted.

Key words: nerve regeneration, neurodegeneration, Bushen Tiansui decoction, Alzheimer’s disease, synaptic plasticity, amyloid β, synaptic proteins, Shank1, N-methyl-D-aspartate receptor 2B subunit, postsynaptic density protein 95, Morris water maze, neural regeneration