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 (3): 449-455.doi: 10.4103/1673-5374.228727

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

阿的平预处理通过稳定细胞膜减少微波辐射造成的神经细胞损伤

  

  • 收稿日期:2017-02-15 出版日期:2018-03-15 发布日期:2018-03-15
  • 基金资助:

    国家科技重大项目药品发现技术平台“重大新药创新与开发”，编号：2012ZX09J12201-005；国家自然科学基金，编号：31071042，31200822；北京市自然科学基金，编号：第5122033号。

Quinacrine pretreatment reduces microwave-induced neuronal damage by stabilizing the cell membrane

Xue-feng Ding1, Yan Wu1, Wen-rui Qu2, Ming Fan1, Yong-qi Zhao1   

  1. 1 Department of Cognitive Sciences, Beijing Institute of Basic Medical Sciences, Beijing, China
    2 Hand & Foot Surgery and Reparative & Reconstructive Surgery Center, Orthopedic Hospital of the Second Hospital of Jilin University,Changchun, Jilin Province, China
  • Received:2017-02-15 Online:2018-03-15 Published:2018-03-15
  • Contact: Yong-qi Zhao, Ph.D. or Ming Fan, Ph.D.,yqzhaoprc@sina.com or fanmingchinaa@126.com.
  • Supported by:

    This work was supported by the Integrated Drug Discovery Technology Platform of National Science and Technology Major Projects for “Major New Drugs Innovation and Development”, No. 2012ZX09J12201-005; the National Natural Science Foundation of China, No.31071042, 31200822; and a grant of Beijing Natural Science Foundation, No. 5122033.

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摘要：

有研究表明抗寄生虫病药物阿的平具有细胞膜结合作用。课题组前期研究发现阿的平预处理能减轻微波辐射诱导大鼠的海马神经元损伤，然而确切分子机制尚不明确。考虑到微波辐射的热效应，以及阿的平对热致细胞损伤的保护作用，我们假设阿的平能预防微波辐射对细胞的损伤作用，其机制与细胞膜稳定作用有关。鉴于此，实验用维甲酸诱导PC12细胞为神经元样细胞，提前给予两种不同剂量阿迪平(20，40 mM)处理，采用50 mW/cm2的高功率微波照射细胞3，6 h。以流式细胞术，原子力显微镜观察和Western blot分析表明，与单纯微波处理组比较，阿的平预处理的细胞经微波照射3，6 h后，细胞凋亡、坏死率、细胞膜结构损伤程度显著降低，热休克蛋白70表达增加。这些结果可以初步解释，阿的平有可能通过上调热休克蛋白70的表达而稳定神经细胞膜结构，从而减轻微波辐射造成的神经细胞损伤的作用及机制。

orcid: 0000-0002-3758-0323(Yong-qi Zhao)
          0000-0002-4447-1598(Ming Fan)

 

关键词: 神经再生, 阿的平, 微波, 辐射, 热休克, 细胞凋亡, 细胞坏死, 热效应, 细胞膜, 热休克蛋白70, 神经细胞

Abstract:

Quinacrine, widely used to treat parasitic diseases, binds to cell membranes. We previously found that quinacrine pretreatment reduced microwave radiation damage in rat hippocampal neurons, but the molecular mechanism remains poorly understood. Considering the thermal effects of microwave radiation and the protective effects of quinacrine on heat damage in cells, we hypothesized that quinacrine would prevent microwave radiation damage to cells in a mechanism associated with cell membrane stability. To test this, we used retinoic acid to induce PC12 cells to differentiate into neuron-like cells. We then pretreated the neurons with quinacrine (20 and 40 mM) and irradiated them with 50 mW/cm2 microwaves for 3 or 6 hours. Flow cytometry, atomic force microscopy and western blot assays revealed that irradiated cells pretreated with quinacrine showed markedly less apoptosis, necrosis, and membrane damage, and greater expression of heat shock protein 70, than cells exposed to microwave irradiation alone. These results suggest that quinacrine stabilizes the neuronal membrane structure by upregulating the expression of heat shock protein 70, thus reducing neuronal injury caused by microwave radiation.

 

Key words: nerve regeneration, quinacrine, microwave, irradiation, heat shock, cell apoptosis, cell necrosis, thermal effect, cell membrane, heat shock protein 70, nerve cells, neural regeneration