中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (5): 915-922.doi: 10.4103/1673-5374.232487

• 原著:退行性病与再生 • 上一篇    下一篇

中药头顶一颗珠提取物可减轻tau蛋白磷酸化异常

  

  • 收稿日期:2018-03-22 出版日期:2018-05-15 发布日期:2018-05-15
  • 基金资助:

      中国国家自然科学基金项目（81260172, 81660223），湖北省生物资源保护与利用重点实验室开放基金项目（PKLHB1318），湖北民族学院科技创新团队项目（MY2011T005），湖北民族学院博士基金项目（MY2012B015），湖北省自然科学基金项目（2017CFB451）

Trillium tschonoskii maxim extract attenuates abnormal Tau phosphorylation

Hong-Bin Luo1, 2, 3, Nan Shang2, 3, Wen-Zhi Xie2, 3, De-Jian Wen2, 3, Min Qu4, Sheng Huang2, 3, Sha-Sha Fan2, 3, Wei Chen2, 3, Nan-Qiao Mou2, 3, Xiang-Yu Liu2, 3, Qin Chen2, 3, Feng-Feng Xie2, 3, Jun-Xu Li5   

  1. 1 Hubei Key Laboratory of Biological Resource Protection and Utilization, Hubei University for Nationalities, Enshi, Hubei Province, China;
    2 Medical College, Hubei University for Nationalities, Enshi, Hubei Province, China;
    3 Institute of Neurological and Psychiatric Comorbidity, Hubei University for Nationalities, Enshi, Hubei Province, China;
    4 Hubei Provincial Key Laboratory for Applied Toxicology, Hubei Provincial Center for Disease Control and Prevention, Wuhan, Hubei Province, China;
    5 Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA
  • Received:2018-03-22 Online:2018-05-15 Published:2018-05-15
  • Contact: Jun-Xu Li, Ph.D. or Hong-Bin Luo, Ph.D., junxuli@buffalo.edu or luohongbin6809@126.com.
  • Supported by:

    This work was supported in part by grants from the National Natural Science Foundation of China, No. 81260172, 81660223; the Opening Foundation of Hubei Key Laboratory of Biological Resource Protection and Utilization of China, No. PKLHB1318; the Science and Technology Innovation Team Project of Hubei University for Nationalities of China, No. MY2011T005; the Doctoral Fund of Hubei University for Nationalities of China, No. MY2012B015; the Natural Science Foundation of Hubei Province of China, No. 2017CFB451.

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摘要：

大规模流行病学研究发现高同型半胱氨酸血症是阿尔茨海默病的强有力且独立的危险因素之一。头顶一颗珠是一种广泛存在于中国中西部的中药，可改善记忆功能，但目前对于其的作用机制尚无深入研究。作者拟探索头顶一颗珠提取物对高同型半胱氨酸血症诱导认知功能损害的潜在神经保护作用。实验对大鼠连续14d静脉注射400 μg/kg高同型半胱氨酸诱导建立阿尔茨海默病模型，然后连续7d灌胃0.125或0.25 g/kg头顶一颗珠提取物进行治疗。以旷场试验和Morris水迷宫测试自发活动及学习记忆能力，以Western blot 检测海马中tau蛋白及其他参与tau蛋白磷酸化的因子的表达水平，以免疫组化染色检测海马中tau蛋白的阳性反应，以Golgi染色检测海马突触发育情况。结果显示，高同型半胱氨酸损伤大鼠出现学习记忆能力缺陷，且大脑海马中tau磷酸化水平增加，催化性蛋白磷酸酶2A活性降低，海马神经元树突棘数量减少。而中药经头顶一颗珠提取物治疗则能明显逆转上述变化。表明中药头顶一颗珠提取物可减轻高同型半胱氨酸血症导致的海马tau蛋白磷酸化异常，具有改善阿尔茨海默病认知障碍的能力。

orcid:0000-0001-6807-512X(Hong-Bin Luo)

关键词: 神经再生, 头顶一颗珠, 高同型半胱氨酸血症, 阿尔茨海默病, 认知障碍, tau, 突触发育

Abstract:

Large-scale epidemiological studies have found that hyperhomocysteinemia is a powerful, independent risk factor for Alzheimer’s disease.Trillium tschonoskii maxim is a traditional Chinese medicine that is used to promote memory. However, scientific understanding of its mechanism of action is limited. This report studied the potential neuroprotective effects of Trillium tschonoskii maxim extract against homocysteine-induced cognitive deficits. Rats were intravenously injected with homocysteine (400 μg/kg) for 14 days to induce a model of Alzheimer’s disease. These rats were then intragastrically treated with Trillium tschonoskii maxim extract (0.125 or 0.25 g/kg) for 7 consecutive days. Open field test and Morris water maze test were conducted to measure spontaneous activity and learning and memory abilities.Western blot assay was used to detect the levels of Tau protein and other factors involved in Tau phosphorylation in the hippocampus.Immunohistochemical staining was used to examine Tau protein in the hippocampus. Golgi staining was applied to measure hippocampal dendritic spines. Our results demonstrated that homocysteine produced learning and memory deficits and increased levels of Tau phosphorylation,and diminished the activity of catalytic protein phosphatase 2A. The total number of hippocampal dendritic spines was also decreased. Trillium tschonoskii maxim extract treatment reversed the homocysteine-induced changes. The above results suggest that Trillium tschonoskii maxim extract can lessen homocysteine-induced abnormal Tau phosphorylation and improve cognitive deterioration such as that present in Alzheimer’s disease.

Key words: nerve regeneration, Trillium tschonoskii maxim, homocysteine, Alzheimer’s disease, cognitive disorders, Tau, synaptic development, neural regeneration