HO-1基因过表达阻断MLK3/MKK7/JNK信号通路对脊髓损伤保护作用的机制研究

项目名称： HO-1基因过表达阻断MLK3/MKK7/JNK信号通路对脊髓损伤保护作用的机制研究

项目编号： No.81201403

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 林文平

作者单位： 福建医科大学

项目金额： 23万元

中文摘要： 脊髓损伤（Spinal cord injury, SCI）是一种严重损害人类健康的疾患，常导致截瘫或四肢瘫痪、大小便失禁和感觉障碍，给个人、家庭及社会带来沉重的负担。血红素氧合酶-1(Heme Oxygenase-1,HO-1)在SCI中具有重要的神经保护作用，HO-1的表达与JNK信号通路密切相关。迄今，HO-1基因转染是否能够对SCI起神经保护作用？HO-1对SCI的治疗作用是否是通过阻断MLK3/MKK7/JNK信号通路实现的？国内外均未见报道。因此，本项目立足前期研究基础，拟联合慢病毒载体介导的基因过表达技术和siRNA技术来调控HO-1的表达，探讨HO-1基因是否可以通过阻断MLK3/MKK7/JNK信号通路对SCI起保护作用，从而为HO-1用于SCI的治疗提供新思路和新靶点。

中文关键词： 脊髓损伤；基因治疗；血红素氧合酶-1；核苷酸结合寡聚化结构域样受体蛋白1；白细胞介素1β

英文摘要： Spinal cord injury (SCI) refers to a disease that will bring severe negative impact to the health. It would result in paraplegia or quadriplegia，incontinence and sensory disturbances. Anyone who suffers from SCI would become a great burden to the family and society. Heme Oxygenase-1 (HO-1) plays an important role in protecting SCI. The expression of HO-1 closely relates to the JNK signaling pathway. So far there's no report about whether HO-1 gene transfection would protect SCI or whether HO-1 gene overexpression has therapeutic effect on SCI by inactivating the MLK3-MKK7-JNK signaling pathway. Based on our previous research, we aims to adjust different HO-1 expressions with lentivirus-mediated gene overexpressions and siRNA technics, so as to study the effect of HO-1 gene overexpression on SCI and explore its molecular mechanisms, which would provide theoretical basis and experimental evidence for the treatment of SCI.

英文关键词： spinal cord injury；gene therapy；heme oxygenase-1；NOD-like receptor protein-1；interleukin-1β