Wnt-3a/β-catenin/mTOR信号通路对脊髓损伤后自噬的调控作用及机制研究

The regulating effect of wnt-3a/β-catenin canonical signaling pathway on autophagy after spinal cord injury(SCI) has not been illuminated. Our previous study had demonstrated that the expression levels of wnt-3a and β-catenin proteins had the negative correlativity with the expression levels of p-p70S6K proteins, and had positive correlativity with the expression levels of Beclin-1 proteins after SCI. Besides, the neuronal autophagy was obviously activated in the injured rats with treatment by wnt-3a protein. The above results may reveal that the neuronal autophagy was regulated by wnt-3a via the β-catenin and mTOR signaling pathway after SCI. Meanwhile, our study had also discovered that the wnt-3a provided the favorable microenvironment for the recovery of nerve function after SCI. According to our research findings, the study, combining the animal experiments and cell experiments, will reveal the regulating effect of wnt-3a/β-catenin/mTOR signaling pathway on neuronal autophagy, illuminate the specific effect of autophagy regulated with wnt-3a/β-catenin/mTOR signaling pathway on neurological functional recovery in vivo and in vitro experiments after SCI. Our study will explore a potential signaling pathway of regulating the autophagy and provide the theoretical basis and experimental theory for the fundamental research and clinical treatment of spinal cord injury.

Wnt-3a/β-catenin信号通路对脊髓损伤（SCI）后神经元自噬的调控作用尚未得到明确阐述。前期研究发现SCI后wnt信号通路蛋白wnt-3a、β-catenin与自噬信号通路蛋白p-p70S6K呈负相关关系，与自噬蛋白Beclin-1表达水平呈正相关关系，wnt-3a干预SCI大鼠后神经元的自噬活动被激活，提示wnt-3a可能通过β-catenin与mTOR信号通路调控SCI后神经元的自噬。此外，研究发现wnt-3a能够为SCI后神经功能的恢复提供有利的微环境。基于以上研究基础，本项目将结合动物及细胞实验揭示SCI后wnt-3a/β-catenin/mTOR信号通路对神经元自噬的调控作用，阐述wnt-3a/β-catenin/mTOR信号通路调控的自噬对神经功能恢复的具体作用。本课题将探索SCI后神经元自噬的一种新颖信号通路，为SCI的基础与临床研究提供理论学基础与实验学依据。

Wnt-3a/β-catenin信号通路对脊髓损伤（SCI）后神经元自噬的调控作用尚未得到明确阐述。前期研究发现SCI后wnt信号通路蛋白wnt-3a、β-catenin与自噬信号通路蛋白p-p70S6K呈负相关关系，与自噬蛋白Beclin-1表达水平呈正相关关系，wnt-3a干预SCI大鼠后神经元的自噬活动被激活，提示wnt-3a可能通过β-catenin与mTOR信号通路调控SCI后神经元的自噬。此外，研究发现wnt-3a能够为SCI后神经功能的恢复提供有利的微环境。基于以上研究基础，本项目将结合动物及细胞实验揭示SCI后wnt-3a/β-catenin/mTOR信号通路对神经元自噬的调控作用，阐述wnt-3a/β-catenin/mTOR信号通路调控的自噬对神经功能恢复的具体作用。本课题将探索SCI后神经元自噬的一种新颖信号通路，为SCI的基础与临床研究提供理论学基础与实验学依据。