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 (2): 301-306.doi: 10.4103/1673-5374.200813

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

中药复方天泰1号对SAMP8小鼠的神经保护及相关分子机制

  

  • 收稿日期:2016-12-28 出版日期:2017-02-15 发布日期:2017-02-15
  • 基金资助:

    国家自然科学基金（81473742）；广东科技项目（2013b021800101）；深圳科技规划重大项目（jcyj20130401115231337）。

Neuroprotective effect of the Chinese medicine Tiantai No. 1 and its molecular mechanism in the senescence-accelerated mouse prone

Ying-hong Li1, Xu-sheng Wang2, Xiao-lin Chen3, Yu Jin1, Hong-bo Chen4, Xiu-qin Jia1, Yong-feng Zhang1, Zheng-zhi Wu1   

  1. 1 First Affiliated Hospital of Shenzhen University (Shenzhen Second People’s Hospital), Shenzhen, Guangdong Province, China; 
    2 School of Life Sciences, Tsinghua University, Beijing, China; 
    3 Guangzhou Medical University, Guangzhou, Guangdong Province, China; 
    4 Shenzhen Key Laboratory of Health Sciences and Technology, Graduate School at Shenzhen, Tsinghua University, Beijing, China
  • Received:2016-12-28 Online:2017-02-15 Published:2017-02-15
  • Contact: Zheng-zhi Wu,yinghongli@163.com or szwzz001@163.com.
  • Supported by:

    This study was funded by the National Natural Science Foundation of China, No. 81473742; the Guangdong Science and Technology Foundation, No. 2013B021800101; the Shenzhen Major Project of Science and Technology Planning, No. JCYJ20130401115231337.

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摘要：

 

以纯天然中药天麻，人参和银杏叶粉按照2:1:2的比例用纯净水溶解和稀释混匀配制的中药复方天泰1号，对多种认知障碍的动物模型有神经保护作用，但作用分子机制尚不清楚。为此，实验设计选用SAMP8阿尔茨海默病模型小鼠，用天泰1号50, 100和150 mg/kg/d分别灌胃8周，观察Morris水迷宫实验显示，SAMP8小鼠逃避潜伏期缩短；空间探索试验中可增加游泳距离在目标象限中所占的百分比，表明天泰1号可以改善SAMP8小鼠学习和记忆能力。进一步的免疫组织化学分析显示，在天泰1号处理组中海马区标记细胞增殖状态的抗原-Ki67阳性细胞明显升高，海马区星形胶质细胞数量降低，β-淀粉样蛋白的积累和Tau蛋白磷酸化水平降低。整体结果显示，天泰1号可通过改善阿尔茨海默病小鼠模型中海马区细胞的增殖潜力，减少星形胶质细胞的渗透，降低β-淀粉样蛋白的积累和Tau蛋白磷酸化，从而发挥神经保护作用。

ORCID:0000-0002-1963-8560(Ying-hong Li);0000-0002-8819-609X(Zheng-zhi Wu)

关键词: 神经再生, 神经退行性变, 阿尔茨海默病, 天泰1号, 神经保护作用, SAMP8 , β淀粉样, 自噬溶酶体途径, 泛素蛋白酶体途径, Tau蛋白磷酸化, 神经细胞凋亡, 星形细胞增生

Abstract:

Tiantai No. 1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2:1:2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No. 1 intragastrically to senescence-accelerated mouse prone 8 (SAMP8) mice (a model of Alzheimer’s disease) at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer’s disease-related proteins in the brain. Tiantai No. 1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No. 1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No. 1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No. 1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No. 1 is neuroprotective in the SAMP8 mouse model of Alzheimer’s disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.

Key words: nerve regeneration, neuroprotective effects, Alzheimer’s disease, Tiantai No. 1, SAMP8, amyloid-beta, autophagy-lysosome pathway,
ubiquitin proteasome pathway, tau phosphorylation, neuronal apoptosis, astrocytosis, neural regeneration