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 (2): 340-346.doi: 10.4103/1673-5374.226404

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

电刺激促进损伤脊髓电生理功能恢复：作用途径涉及p38-RhoA和ERK1/2-Bcl-2通路？

  

  • 收稿日期:2018-01-19 出版日期:2018-02-15 发布日期:2018-02-15
  • 基金资助:

    韩国Wonkwang临床医学研究所资助项目

Effect of electrical stimulation on neural regeneration via the p38-RhoA and ERK1/2-Bcl-2 pathways in spinal cord-injured rats

Min Cheol Joo1, Chul Hwan Jang1, Jong Tae Park2, Seung Won Choi3, Seungil Ro4, Min Seob Kim5, Moon Young Lee5   

  1. 1 Department of Rehabilitation Medicine and Institute of Wonkwang Medical Science, School of Medicine, Wonkwang University, Iksan,South Korea
    2 Department of Neurosurgery, School of Medicine, Wonkwang University, Iksan, South Korea
    3 Department of Anesthesiology and Pain Medicine, School of Medicine, Wonkwang University, Iksan, South Korea
    4 Department of Physiology and Cell Biology, School of Medicine, University of Nevada, Reno, NV, USA
    5 Department of Physiology and Institute of Wonkwang Medical Science, School of Medicine, Wonkwang University, Iksan, South Korea
  • Received:2018-01-19 Online:2018-02-15 Published:2018-02-15
  • Contact: Moon Young Lee, M.D., Ph.D.,lmy6774@wku.ac.kr.
  • Supported by:

    This study was supported by a grant from Wonkwang Institute of Clinical Medicine in 2011.

PDF

276

摘要：

尽管电刺激（ES）在临床试验中已证实有促进神经再生的作用，但其在受损脊髓中如何在分子水平上发挥作用尚不清楚。为研究ES改善受损脊髓功能涉及的信号通路，实验将21只雌性SD大鼠随机分为对照组（未进行手术干预，n = 6），SCI组（仅SCI，n = 5）和电刺激组（脊髓损伤后进行电刺激，n = 10）。首先建立第10节胸髓完全横断模型后，对受伤脊髓区域进行电刺激干预，每天施用4 h，持续7 d。伤后第2和7天，以Touch-Test感觉评估测试和BBB评分评估大鼠感觉和运动功能；对大鼠后肢胫神经进行体感诱发电位检测，以评估脊髓电生理功能；应用免疫印迹法检测大鼠损伤脊髓p38-RhoA和ERK1/2-Bcl-2通路蛋白水平；脊髓损伤组与电刺激组大鼠感觉和运动功能相近。相较于脊髓损伤组，电刺激组大鼠胫神经体感诱发电位潜伏期明显缩短，波幅明显升高；损伤脊髓中RhoA蛋白水平明显降低，而蛋白基因产物9.5，细胞外信号调节激酶1/2，p38和Bcl-2蛋白水平明显升高。这些数据结果表明，电刺激可能通过影响受损脊髓p38-RhoA和细胞外信号调节激酶1/2-Bcl-2通路，达到促进脊髓电生理功能恢复的目的。

orcid:0000-0003-4956-9241(Moon Young Lee)

关键词: Bcl-2, 细胞外信号调节激酶1/2, p38, 蛋白基因产物9.5, RhoA, 脊髓损伤, 体感诱发电位, 肌肉收缩, 电脉冲, 神经再生

Abstract:

Although electrical stimulation is therapeutically applied for neural regeneration in patients, it remains unclear how electrical stimulation exerts its effects at the molecular level on spinal cord injury (SCI).To identify the signaling pathway involved in electrical stimulation improving the function of injured spinal cord, 21 female Sprague-Dawley rats were randomly assigned to three groups: control (no surgical intervention, n = 6), SCI (SCI only, n = 5), and electrical simulation (ES; SCI induction followed by ES treatment, n = 10). A complete spinal cord transection was performed at the 10th thoracic level. Electrical stimulation of the injured spinal cord region was applied for 4 hours per day for 7 days. On days 2 and 7 post SCI, the Touch-Test Sensory Evaluators and the Basso-Beattie-Bresnahan locomotor scale were used to evaluate rat sensory and motor function. Somatosensory-evoked potentials of the tibial nerve of a hind paw of the rat were measured to evaluate the electrophysiological function of injured spinal cord. Western blot analysis was performed to measure p38-RhoA and ERK1/2-Bcl-2 pathways related protein levels in the injured spinal cord. Rat sensory and motor functions were similar between SCI and ES groups. Compared with the SCI group, in the ES group, the latencies of the somatosensory-evoked potential of the tibial nerve of rats were significantly shortened, the amplitudes were significantly increased, RhoA protein level was significantly decreased, protein gene product 9.5 expression, ERK1/2, p38, and Bcl-2 protein levels in the spinal cord were significantly increased. These data suggest that ES can promote the recovery of electrophysiological function of the injured spinal cord through regulating p38-RhoA and ERK1/2-Bcl-2 pathway-related protein levels in the injured spinal cord.

Key words: Bcl-2, ERK1/2, p38, PGP9.5, RhoA, spinal cord injury, somatosensory evoked potential, muscle contraction, electrical impulses, neural regeneration