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 (10): 1833-1841.doi: 10.4103/1673-5374.238620

• 原著:退行性病与再生 • 上一篇    下一篇

50Hz高频电针可改善Aβ1-42诱导阿尔茨海默病模型大鼠的认知功能障碍

  

  • 收稿日期:2018-07-14 出版日期:2018-10-15 发布日期:2018-10-15
  • 基金资助:

    中国国家自然科学基金项目（81373741），湖北省卫计委中医药中西医结合医药研究项目（24），湖北省针灸预防创新合作中心项目（2014, No. 8）

High-frequency (50 Hz) electroacupuncture ameliorates cognitive impairment in rats with amyloid beta 1–42-induced Alzheimer’s disease

Chao-Chao Yu1, Ying Wang1, Feng Shen2, Li-Hong Kong2, Ya-Wen Wang2, Hua Zhou2, Lei Tang3   

  1. 1 Hubei University of Chinese Medicine, Wuhan, Hubei Province, China
    2 Department of Acupuncture and Moxibustion, College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine, Wuhan, Hubei Province, China
    3 Department of Rehabilitation, Wuhan Central Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China
  • Received:2018-07-14 Online:2018-10-15 Published:2018-10-15
  • Contact: Li-Hong Kong,xiyu1618@sina.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81373741; a grant from the Chinese Medicine and Integrated Medicine Research Projects funded by the Health and Family Planning Commission of Hubei Province of China, No. 24; a grant from the Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion of China in 2014, No. 8.

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摘要：

既往研究已证实针灸可改善阿尔茨海默病的认知障碍，其中刺激穴位和频率对电针治疗效果具有重要影响。实验通过双侧脑室注射Aβ1–42建立阿尔茨海默病大鼠模型，然后以2，30，50Hz电针刺激百会(GV20；倾斜15°，深度2mm)和交替针刺肾俞(BL23；垂直针刺4-6mm)，1次/d，20min/次，连续15d，每7d休息一次。(1)以Morris水迷宫评价空间学习记忆能力，以Western blot检测海马组织中糖原合成酶激酶3β、Ser9位点磷酸化糖原合成酶激酶3β、Tyr216位点磷酸化糖原合成酶激酶3β、淀粉样前体蛋白和Aβ1-40的表达。(2)结果显示，经不同频率电针刺激后，大鼠的学习记忆能力明显改善，海马组织中突触曲度增加，突触间隙宽度减少，突触后密度增加，糖原合成酶激酶3β、淀粉样前体蛋白和Aβ1-40表达下降，Ser9位点磷酸化糖原合成酶激酶3β表达减少，而Tyr216位点磷酸化糖原合成酶激酶3β表达增加，且与低频（2Hz）和中频（30Hz）相比，高频（50Hz）电针刺激的治疗效果更好。提示电针可通过抑制糖原合成酶激酶3β活性对Aβ1-40诱导的学习记忆缺陷和突触超微结构损伤具有保护作用，且高频电针表现出较好的治疗效果。

orcid:0000-0002-4287-0536(Li-Hong Kong)

关键词: 电针, 频率, 阿尔茨海默病, 认知障碍, 海马, 糖原合成酶激酶3&beta, 突触曲率, 突触间隙宽度, 突触后密度, 百会（GV20）, 肾俞（BL23）, 神经再生

Abstract:

Acupuncture has been shown to ameliorate cognitive impairment of Alzheimer’s disease. Acupoints and stimulation frequency influence the therapeutic effect of electroacupuncture. Rat models of Alzheimer’s disease were established by injecting amyloid beta 1–42 (Aβ1–42) into the bilateral lateral ventricles. Electroacupuncture at 2, 30, and 50 Hz was carried out at Baihui (GV20; 15° obliquely to a depth of 2 mm) and Shenshu (BL23; perpendicularly to 4–6 mm depth), once a day for 20 minutes (each), for 15 days, taking a break every 7 days. The Morris water maze test was conducted to assess the learning and memory. The expression levels of glycogen synthase kinase-3β (GSK-3β), pSer9-GSK-3β, pTyr216-GSK-3β, amyloid precursor protein and Aβ1–40 in the hippocampus were determined by western blot assay. Results demonstrated that electroacupuncture treatment at different frequencies markedly improved learning and memory ability,increased synaptic curvatures, decreased the width of synaptic clefts, thickened postsynaptic densities, and downregulated the expression of GSK-3β, amyloid precursor protein, and Aβ1–40. pSer9-GSK-3β expression markedly decreased, while pTyr216-GSK-3β expression increased. High-frequency (50 Hz) electroacupuncture was more effective than low (2 Hz) or medium-frequency (30 Hz) electroacupuncture. In conclusion, electroacupuncture treatment exerts a protective effect against Aβ1–42-induced learning and memory deficits and synapse-ultrastructure impairment via inhibition of GSK-3β activity. Moreover, high-frequency electroacupuncture was the most effective therapy.

Key words: nerve regeneration, electroacupuncture, different frequencies, Alzheimer’s disease, cognitive impairment, hippocampus, glycogen synthase kinase-3β, synaptic curvatures, width of synaptic cleft, postsynaptic density, Baihui (GV20), Shenshu (BL23), neural regeneration