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间充质干细胞源性外泌体对正己烷中毒大鼠神经组织受损轴突修复作用及机制研究

间充质干细胞源性外泌体对正己烷中毒大鼠神经组织受损轴突修复作用及机制研究
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  • 批准号:81773402
  • 批准年度: 2017年
  • 学科分类:职业卫生(H2602) |
  • 项目负责人:朴丰源
  • 负责人职称:教授
  • 依托单位:大连医科大学
  • 资助金额:60万元
  • 项目类别:面上项目
  • 研究期限:2018年01月01日 至 2021年12月31日
  • 中文关键词: 间充质干细胞源性外泌体;正己烷中毒;大鼠;神经组织;轴突
  • 英文关键词:N-hexane poisoning;mesenchymal stem cell - derived exosomes;nerve growth factor;axonal injury; repai

项目摘要

中文摘要

慢性正己烷中毒是我国严重职业病,可诱发轴索变性为特征的中枢-周围神经病。然而,尚无有效干预手段恢复其严重受损神经功能。干细胞外泌体能模拟干细胞生物学功能,对轴突损伤有修复作用。根据文献分析和前期研究,申请者提出干细胞外泌体介导NGF促进正己烷中毒大鼠轴突再生修复机制假设,为本课题立项奠定理论基础。本研究构建正己烷中毒和间充质干细胞外泌体干预大鼠模型及原代神经元模型;用神经损伤检测平台、电生理技术和形态学观察,评价神经功能恢复和轴突修复程度;用免疫荧光技术检测Texas-red标记间充质干细胞外泌体在受损神经组织靶向分布;用RNA沉默技术、荧光素酶报告基因技术等,探讨干细胞外泌体介导NGF依赖性激活PI3K/Akt通路及下游信号,促进正己烷中毒大鼠轴突再生修复作用及机制。本研究将为慢性正己烷中毒神经组织损伤修复,提供干细胞外泌体干预新方法,也为其它化学物暴露所致神经组织损伤修复提供参考依据。

英文摘要

Chronic n-hexane poisoning is a serious occupational disease in China, it could induce central-peripheral neuropathy which is characterized by axonal degeneration. However, there is no effective treatment to restore its severely impaired nerve function. Stem cell-derived exosomes have the similar biological function with stem cells and could recover the axon injury. According to the literatures and previous studies, the applicant put forward the hypothesis that stem cell-derived exosomes could promote the regeneration of axon in rats with n-hexane exposure, laying the theoretical foundation for this study. In this study, we established the model of mesenchymal stem cell-derived exosomes treatment to the exposure to n-hexane in rats and primary neuron in vitro. The nerve damage detecting platform, electrophysiological technique and morphological observation were used to evaluate the recovery of nerve function and the degree of axon repair. Moreover, immunofluorescence technique was used to detect the targeted distribution of Texas-red-labeled mesenchymal stem cells exosomes in the damaged nerve tissue. Besides, the gene technique and luciferase reporter gene technique were also used to explore the mechanism that the exosomes by NGF-dependent PI3K/Akt pathway and downstream signaling promotes the axonal regeneration in n-hexane poisoning rats. This study will provide a new method for the treatment of nerve tissue damage caused by chronic exposure to n-hexane, and also provide reference for the repair of nerve tissue injury caused by exposure to other chemicals.

评估说明

    国家自然科学基金项目“间充质干细胞源性外泌体对正己烷中毒大鼠神经组织受损轴突修复作用及机制研究”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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