中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (12): 2025-2034.doi: 10.4103/1673-5374.221160

• 原著:退行性病与再生 • 上一篇    下一篇

 
红景天提取物对阿尔茨海默病大鼠海马神经元具有保护线粒体和抗凋亡作用

  

  • 收稿日期:2017-09-05 出版日期:2017-12-15 发布日期:2017-12-15
  • 基金资助:

    广东省中医药局科技项目(2007109),广东省医科科研项目(A20111154

Mitochondrial protective and anti-apoptotic effects of Rhodiola crenulata extract on hippocampal neurons in a rat model of Alzheimer’s disease

Jun-mei Wang1, Ze-qiang Qu1, Jin-lang Wu2, Peter Chung3, Yuan-shan Zeng1, 4, 5, 6   

  1. 1 Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China
    2 Department of Electron Microscope, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province, China
    3 Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
    4 Institute of Spinal Cord Injury, Sun Yat-sen University, Guangzhou, Guangdong Province, China
    5 Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China
    6 Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou,Guangdong Province, China
  • Received:2017-09-05 Online:2017-12-15 Published:2017-12-15
  • Contact: Yuan-shan Zeng, M.D., Ph.D.,zengysh@mail.sysu.edu.cn.
  • Supported by:

    This study was supported by grants of the Administrative Bureau of Chinese Traditional Medicine of Guangdong Province of China,No. 2007109; and the Medical Research Foundation of Guangdong Province of China, No. A20111154.

摘要:

作者既往研究发现,药用植物红景天根部的乙醇提取物能改善阿尔茨海默病模型大鼠空间认知能力,但其机制仍不明朗。作者所在团队另一项研究显示红景天根部的乙醇提取物能够促进慢性应激引起的抑郁大鼠海马齿状回中神经细胞的增殖,减轻海马神经细胞损伤。实验设计观察确定红景天根部的乙醇提取物对阿尔茨海默病大鼠线粒体保护机制和抗凋亡作用。采用侧脑室注射链脲佐菌素建立阿尔茨海默病大鼠模型,在造模前21d每天以1.5,3.0,6.0 g/kg红景天根部的乙醇提取物灌胃。结果发现,阿尔茨海默病模型大鼠海马线粒体ATP和细胞色素氧化酶水平降低,且海马区神经元损伤明显,出现大量凋亡神经元;而经不同浓度红景天根部的乙醇提取物预处理,大鼠海马线粒体ATP和细胞色素氧化酶至正常水平,神经元凋亡减少,海马神经元中线粒体的损伤减轻,且其中3.0g/kg红景天根部的乙醇提取物作用效果最佳。表明红景天根部的乙醇提取物预处理可减轻海马神经元线粒体的损伤,减少神经元凋亡,对阿尔茨海默病大鼠海马神经元起保护作用。

orcid:0000-0003-3804-5792(Yuan-shan Zeng)

关键词: 神经再生, 阿尔茨海默病, 侧脑室, 链脲佐菌素, 神经元, 细胞凋亡, 神经保护, 细胞色素氧化酶, ATP, Caspase-3, NeuN

Abstract:

In our previous study, we found that the edible alcohol extract of the root of the medicinal plant Rhodiola crenulata (RCE) improved spatial cognition in a rat model of Alzheimer’s disease. Another study from our laboratory showed that RCE enhanced neural cell proliferation in the dentate gyrus of the hippocampus and prevented damage to hippocampal neurons in a rat model of chronic stress-induced depression.However, the mechanisms underlying the neuroprotective effects of RCE are unclear. In the present study, we investigated the anti-apoptotic effect of RCE and its neuroprotective mechanism of action in a rat model of Alzheimer’s disease established by intracerebroventricular injection of streptozotocin. The rats were pre-administered RCE at doses of 1.5, 3.0 or 6.0 g/kg for 21 days before model establishment.ATP and cytochrome c oxidase levels were significantly decreased in rats with Alzheimer’s disease. Furthermore, neuronal injury was obvious in the hippocampus, with the presence of a large number of apoptotic neurons. In comparison, in rats given RCE pretreatment, ATP and cytochrome c oxidase levels were markedly increased, the number of apoptotic neurons was reduced, and mitochondrial injury was mitigated. The 3.0 g/kg dose of RCE had the optimal effect. These findings suggest that pretreatment with RCE prevents mitochondrial dysfunction and protects hippocampal neurons from apoptosis in rats with Alzheimer’s disease.

Key words: nerve regeneration, Alzheimer’s disease, intracerebroventricular injection, streptozotocin, neuronal apoptosis, neuroprotection, cytochrome c oxidase, adenosine triphosphate, caspase-3, NeuN, neural regeneration