中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (10): 1687-1694.doi: 10.4103/1673-5374.217348

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

 聚乙烯亚胺-藻酸盐纳米颗粒携带Nischarin-siRNA促进脊髓损伤后运动功能的恢复

  

  • 收稿日期:2017-08-20 出版日期:2017-10-15 发布日期:2017-10-15
  • 基金资助:

    浙江省自然科学基金（ly15h250001，ly14h090002）；国家自然科学基金（81000535，81402872）；浙江省医疗科技项目基金（2014kya166）；浙江省科技高创新人才发展规划的基础（2014r401186）

Nischarin-siRNA delivered by polyethylenimine-alginate nanoparticles accelerates motor function recovery after spinal cord injury

Yue-min Ding1, Yu-ying Li2, Chu Wang1, Hao Huang1, Chen-chen Zheng1, Shao-han Huang1, Yang Xuan1, Xiao-yi Sun3, Xiong Zhang4   

  1. 1 Department of Clinical Medicine, School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang Province, China
    2 Department of Physiology, School of Medicine, Quzhou College of Technology, Quzhou, Zhejiang Province, China
    3 Department of Pharmacy, Zhejiang University City College, Hangzhou, Zhejiang Province, China
    4 Department of Basic Medicine, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
  • Received:2017-08-20 Online:2017-10-15 Published:2017-10-15
  • Contact: Xiong Zhang, Ph.D. or Xiao-yi Sun, Ph.D.,xiongzhang@zju.edu.cn or sunxiaoyi@zucc.edu.cn.
  • Supported by:

    This work was supported by the Natural Science Foundation of Zhejiang Province of China, No. LY15H250001 and LY14H090002;the National Natural Science Foundation of China, No. 81000535 and 81402872; the Medical Science and Technology Project Foundation of Zhejiang Province of China, No. 2014KYA166; and the Science and Technology Innovation Talents Development Plan Foundation for High School Students in Zhejiang Province of China, No. 2014R401186.

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摘要：

 课题组前期研究发现，抑制Nischarin蛋白能促进neuro-2a神经细胞和原代皮质神经元突起生长和再生。我们假设携带针对Nischarin的小干扰RNA(Nis-siRNA)可促进脊髓损伤后运动功能的恢复。实验假设将脊髓半横断损伤模型大鼠的脊髓损伤区一次性直接微量注射5 μL的PEI-ALG/Nis-siRNA，从注射后7天起，PEI-ALG/Nis-siRNA干预的模型大鼠BBB评分显著升高；注射后21 d，苏木精伊红染色显示，脊髓组织的坏死区面积明显减少；免疫组织化学染色及Western blot检测显示，大鼠脊髓组织Nischarin蛋白表达被成功抑制，生长相关蛋白43蛋白表达增加。结果证实，聚乙烯亚胺-藻酸盐纳米颗粒携带的Nischarin-siRNA能有效抑制损伤脊髓组织Nischarin蛋白的表达，诱导生长相关蛋白43表达，促进脊髓损伤后运动功能的恢复。 第

orcid:0000-0003-2235-569X(Xiong Zhang)    0000-0002-6864-1715(Xiao-yi Sun)

关键词: 脊髓损伤, 聚乙烯亚胺, 海藻酸钠, 纳米颗粒, nischarin , 小干扰RNA , 坏死区, 大鼠, 生长相关蛋白43 , 运动功能

Abstract:

A previous study by our group found that inhibition of nischarin promotes neurite outgrowth and neuronal regeneration in Neuro-2a cells and primary cortical neurons. In recent years, more and more studies have shown that nanomaterials have good prospects in treatment of spinal cord injury. We proposed that small interfering RNA targeting nischarin (Nis-siRNA) delivered by polyethyleneimine-alginate (PEIALG) nanoparticles promoted motor function recovery in rats with spinal cord injury. Direct microinjection of 5 μL PEI-ALG/Nis-siRNA into the spinal cord lesion area of spinal cord injury rats was performed. From day 7 after surgery, Basso, Beattie and Bresnahan score was significantly higher in rats from the PEI-ALG/Nis-siRNA group compared with the spinal cord injury group and PEI-ALG/Control-siRNA group. On day 21 after injection, hematoxylin-eosin staining showed that the necrotic area was reduced in the PEI-ALG/Nis-siRNA group. Immunohistochemistry and western blot assay results confirmed successful inhibition of nischarin expression and increased protein expression of growth-associated protein-43 in the PEI-ALG/Nis-siRNA group. These findings suggest that a complex of PEI-ALG nanoparticles and Nis-siRNA effectively suppresses nischarin expression, induces expression of growth-associated protein-43, and accelerates motor function recovery after spinal cord injury.

Key words: nerve regeneration, spinal cord injury, polyethylenimine, alginate, nanoparticles, nischarin, small interfering RNA, necrotic area, growth-associated protein-43, motor function, neural regeneration