Netrin-1在康复训练促进大鼠脑缺血后神经重塑和功能重建中的作用及相关分子机制研究

项目名称： Netrin-1在康复训练促进大鼠脑缺血后神经重塑和功能重建中的作用及相关分子机制研究

项目编号： No.81472161

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘楠

作者单位： 福建医科大学

项目金额： 72万元

中文摘要： 急性缺血性脑损伤后，神经重塑是由神经突起生长并建立新的突触联系所完成的，此过程是神经功能恢复的基础，而康复训练能够促进此过程。我们前期工作观察到康复训练能够提高大鼠脑缺血后脑内Netrin-1及其受体DCC的表达水平，并与脑缺血后的神经重塑和功能恢复相关。既往体外实验也发现，Netrin-1与其受体DCC的结合能活化JNK1/c-Jun信号通路参与受损神经突起的再生。但目前仍不明确Netrin-1介导的JNK1/c-Jun信号通路激活是否涉及康复训练后脑缺血神经重塑和功能重建。本项目拟在前期工作基础上，利用RNA干扰、基因过表达和JNK/c-jun信号通路特异性抑制剂等技术，通过体内外实验，探讨Netrin-1及其介导的JNK1/c-Jun信号通路在康复训练促进大鼠脑缺血性损伤后神经重塑和功能重建中的作用及相关分子机制，为脑缺血后康复训练的临床应用提供新的理论依据。

中文关键词： Netrin-1；神经重塑；信号通路；脑缺血；康复训练

英文摘要： After acute cerebral ischemia occurs, the neural plasticity is contributed by nerve axon regeneration and synaptic connections restablishment, which is the basis of neurological recovery.And treadmill exercise can facilitate this process.Our previous work has observed that treadmill exercise can up-regulation the expression of Netrin-1 and its receptor DCC in brain after cerebral ischemia, and closely related with neural plasticity and functional reconstruction.Previous experiments in vitro also showed that Netrin-1 binding to its receptor DCC can activate JNK1/c-Jun signaling pathway involved in the regeneration of damaged nerve axon. It remains unclear whether Netrin-1-mediated JNK1/c-Jun signaling pathway activation involves in exercise-induced nerve remodeling and reconstruction after brain ischemia. Based on previous work，laying on the animal and cellular level, using multi-level blocking technologies such as RNA interference,gene overexpression and JNK/c-Jun signaling pathway inhibitor,we seek to explore the role and relevant molecular mechanism of Netrin-1-mediated the JNK1/c-Jun signaling pathway in treadmill exercise-induced nerve remodeling and reconstruction，and provide a new theoretical foundation for the clinical application of treadmill exercise.

英文关键词： Netrin-1;neural plasticity;signaling pathway;cerebral ischemia;treadmill exercise