AMPK-mTOR信号通路在脊髓损伤(SCI)后自噬中发挥重要作用，而锌转运蛋白3（ZnT3）可调节神经突触前膜释放ACh促进神经功能恢复。前期研究发现：SCI后ZnT3表达及局部ACh含量均明显增高，ZnT3与自噬水平呈正相关关系，而与mTOR表达呈负相关关系。因此我们提出：ZnT3可能通过ACh-AMPK-mTOR诱导SCI后自噬发生。本项目将利用ZnT3基因敲除小鼠构建SCI模型，检测此类小鼠SCI后运动神经功能的恢复情况；并培养其原代神经元细胞，观察研究损伤处理后的细胞及突触形态变化；探讨基因沉默/过表达对脊髓运动神经元细胞株损伤后超微结构、增殖及能量代谢的影响，检测自噬相关蛋白表达的变化；阐明SCI后调控自噬的ZnT3-ACh-AMPK-mTOR信号通路的具体分子机制。本项目的顺利进行将为SCI提供新的治疗靶点及方案，为SCI的基础研究提供有力的理论学依据和实验学基础。

AMPK-mTOR signaling pathway plays an important role in autophagy after spinal cord injury (SCI). Zinc transporter protein 3 (ZnT3) can regulate the release of ACh of nerve presynaptic membrane, which promotes the recovery of neurological function. Previous studies have found that the ZnT3 and local ACh expression levels were significantly increased, the expression levels of ZnT3 and autophagy were positive correlativity, on the contrary, the expression of ZnT3 and mTOR protein was negative correlativity after SCI. Therefore, we have supposed that ZnT3 may induced autophagy by ACh-AMPK-mTOR signaling pathway. In our study, we will establish SCI model by utilizing ZnT3 knockout mouse, detect the recovery of their locomotor and nerve function. Besides, we will observe morphological changes of the cells and synapse after culturing spinal cord primary neuronal cells. Furthermore, we will observe the ultrastructure, proliferation and energy metabolism in the spinal motor neuron cells after ZnT3 gene silencing or overexpression, and detect the activity of autophagy after injury. Finally, our study will illuminate the specific molecular mechanisms on regulation of autophagy with ZnT3-ACh-AMPK-mTOR signaling pathway after SCI. The study will provide new therapeutic targets and scheme for SCI, and offer a strong basis of theoretical and experimental foundation for fundamental research of SCI.