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 (1): 112-118.doi: 10.4103/1673-5374.224380

• 原著:退行性病与再生 • 上一篇    下一篇

艾灸对鱼藤酮诱导帕金森病模型大鼠mTOR介导自噬的影响

  

  • 收稿日期:2017-10-25 出版日期:2018-01-15 发布日期:2018-01-15
  • 基金资助:

    国家自然科学基金（81403456，81473788）；湖北省针灸预防治疗协作创新中心项目（HBPCIC-2016-003）

 Effect of moxibustion on mTOR-mediated autophagy in rotenone-induced Parkinson’s disease model rats

Shu-ju Wang, Qi Wang, Jun Ma, Pei-hao Yu, Zhong-ming Wang, Bin Wang   

  1. Hubei University of Chinese Medicine/Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and  Moxibustion, Wuhan, Hubei Province, China
  • Received:2017-10-25 Online:2018-01-15 Published:2018-01-15
  • Contact: Jun Ma, M.D.,mj-1964@163.com.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81403456, 81473788; a grant from the Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion, No. HBPCIC-2016-003.

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摘要：

自噬介导的α-突触核蛋白清除作用缺陷可能是导致黑质多巴胺能神经元进行性丢失的关键之一。艾灸疗法治疗帕金森病已被证实有确切疗效，但其机制仍然未知。基于此，我们试图以促进α-突触核蛋白的清除为切入点，观察艾灸干预能否从改善mTOR介导自噬的角度来发挥多巴胺能神经元保护作用。采用颈背部皮下注射鱼藤酮制备帕金森病大鼠模型，选取“足三里”(ST36)(双侧)、“关元”(CV4)、“风府”(GV16)穴施予艾灸治疗，1次/d，每次10 min，连续治疗14 d，并设建模后不予以任何治疗处理的模型组作对照。结果显示：与模型组相比，艾灸组黑质酪氨酸羟化酶免疫反应及LC3-Ⅱ蛋白表达显著增加，行为学评分、α-突触核蛋白免疫反应、p-mTOR和p-p70S6K蛋白表达显著下降。上述结果说明，艾灸可增强mTOR介导对α-突触核蛋白自噬性清除作用，改善帕金森病模型大鼠异常行为学表现，其机制可能与艾灸抑制mTOR/p70S6K通路过度活化相关。

orcid:0000-0003-0015-4184(Jun Ma)

关键词: 神经再生, 神经退行性变, 帕金森病, 针刺, 艾灸, 鱼藤酮, &alpha, -突触核蛋白, 自噬, 哺乳动物雷帕霉素靶蛋白, p-p70S6K, LC3-Ⅱ

Abstract:

Defects in autophagy-mediated clearance of α-synuclein may be one of the key factors leading to progressive loss of dopaminergic neurons in the substantia nigra. Moxibustion therapy for Parkinson’s disease has been shown to have a positive effect, but the underlying mechanism remains unknown. Based on this, we explored whether moxibustion could protect dopaminergic neurons by promoting autophagy mediated by mammalian target of rapamycin (mTOR), with subsequent elimination of α-syn. A Parkinson’s disease model was induced in rats by subcutaneous injection of rotenone at the back of their necks, and they received moxibustion at Zusanli (ST36), Guanyuan (CV4)and Fengfu (GV16), for 10 minutes at every point, once per day, for 14 consecutive days. Model rats without any treatment were used as a sham control. Compared with the Parkinson’s disease group, the moxibustion group showed significantly greater tyrosine hydroxylase immunoreactivity and expression of light chain 3-II protein in the substantia nigra, and their behavioral score, α-synuclein immunoreactivity,the expression of phosphorylated mTOR and phosphorylated ribosomal protein S6 kinase (p-p70S6K) in the substantia nigra were significantly lower. These results suggest that moxibustion can promote the autophagic clearance of α-syn and improve behavioral performance in Parkinson’s disease model rats. The protective mechanism may be associated with suppression of the mTOR/p70S6K pathway.

Key words: nerve regeneration, neurodegeneration, Parkinson’s disease, acupuncture, moxibustion, rotenone, alpha-synuclein, autophagy;phosphorylated mammalian target of rapamycin kinase, phosphorylated ribosomal protein S6 kinase, light chain 3-II, neural regeneration