中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (9): 1492-1498.doi: 10.4103/1673-5374.191224

• 原著:退行性病与再生 • 上一篇    下一篇

雷公藤甲素干预双转基因阿尔茨海默病模型小鼠海马小胶质细胞和星型胶质细胞的变化

  

  • 收稿日期:2016-08-16 出版日期:2016-09-30 发布日期:2016-09-30
  • 基金资助:
    中国博士后科学基金（2016m590757）；湖南省自然科学基金（2015jj6010）；湖南省科技项目（2015jc3059）；湖南省教育部基金（15a023，13c1107）；卫生科研项目基金（b2011-071，b2016096）；湖南市重点学科建设项目

Effects of triptolide on hippocampal microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer’s disease

Jian-ming Li1, 2, 3, 4, Yan Zhang3, Liang Tang3, Yong-heng Chen3, Qian Gao3, Mei-hua Bao3, Ju Xiang3, De-liang Lei2, *   

  1. 1 Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China 2 Department of Anatomy and Neurobiology, Central South University, School of Basic Medical Science, Changsha, Hunan Province, China 3 Neuroscience Research Center, Changsha Medical University, Changsha, Hunan Province, China 4 Department of Anatomy, Changsha Medical University, Changsha, Hunan Province, China
  • Received:2016-08-16 Online:2016-09-30 Published:2016-09-30
  • Contact: De-liang Lei, Ph.D., delianglei@csu.edu.cn.
  • Supported by:
    This study was supported by China Postdoctoral Science Foundation, No. 2016M590757; the Postdoctoral Science Foundation of Xiangya Hospital of Central South University of China, No. 20; the Hunan Provincial Natural Science Foundation of China, No. 2015JJ6010; a grant from the Basic Research Program of Science and Technology Commission Foundation of Hunan Province of China, No. 2015JC3059; the Project Fund of the Department of Education in Hunan Province of China, No. 15A023, 13C1107; the Scientific Research Project Fund of Health Department of Hunan Province of China, No. B2011-071, B2016096; a grant from the Construction Program of the Key Discipline in Hunan Province of China.

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摘要：

阿尔茨海默病的主要病理改变为脑内神经元细胞外β-淀粉蛋白沉积并形成老年斑，这些改变可以引起脑内炎症反应，来自中国的中药雷公藤多甙提取物-雷公藤甲素具有较强的抗炎和免疫抑制功效。为此，我们假设雷公藤甲素可抑制app/ps1双转基因阿尔茨海默病模型小鼠海马小胶质细胞和星型胶质细胞的活化和增殖。实验用1，5 µg/kg/d雷公藤甲素对4.0-4.5月龄的app/ps1双转基因阿尔茨海默病模型小鼠腹腔注射45 d，无偏性体视学定量分析发现，雷公藤甲素呈剂量依赖性降低海马区小胶质细胞的数量，并可能使活化的神经胶质细胞趋向静息状态转化，雷公藤甲素5 µg/kg/d处理还可降低海马区星型胶质细胞数量。体内实验结果显示，雷公藤甲素对app/ps1双转基因阿尔茨海默病模型小鼠海马小胶质细胞和星型胶质细胞活化和增殖，有明确的抑制作用。 

orcid: 0000-0002-1037-7296 (De-liang Lei)

关键词: 神经再生, 神经退行性变, 中医药, 雷公藤多甙, 雷公藤甲素, 阿尔茨海默病, 淀粉样斑块, β淀粉蛋白, 淀粉样前体蛋白, 炎症, 小胶质细胞, 星形胶质细胞

Abstract: The principal pathology of Alzheimer’s disease includes neuronal extracellular deposition of amyloid-beta peptides and formation of senile pl aques, which in turn induce neuroin?ammation in the brain. Triptolide, a natural extract from the vine-like herb Tripterygium wilfordii Hook F, has potent anti-in?ammatory and immunosuppressive effcacy. Therefore, we determined if triptolide can inhibit activation and proliferation of microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer’s disease. We used 1 or 5 μg/kg/d triptolide to treat APP/PS1 double transgenic mice (aged 4–4.5 months) for 45 days. Unbiased stereology analysis found that triptolide dose-dependently reduced the total number of microglial cells, and transformed microglial cells into the resting state. Further, triptolide (5 μg/kg/d) also reduced the total number of hippocampal astrocytes. Our in vivo test results indicate that triptolide suppresses activation and proliferation of microglial cells and astrocytes in the hippocampus of APP/PS1 double transgenic mice with Alzheimer’s disease.

Key words: nerve regeneration, neurodegenerative disease, traditional Chinese medicine, Tripterygium wilfordii Hook F, triptolide, Alzheimer’s disease, amyloid plaques, amyloid-β, amyloid precursor protein, inflammation, microglia, astrocytes, neural regeneration