锌离子通过G-CSF/NRF2/SIRT3通路调控神经元糖代谢促进脊髓损伤神经功能修复的机制研究

脊髓损伤（SCI）后炎症和线粒体代谢的稳态对神经功能恢复具有重要作用，其中赖氨酸乙酰化/ 去乙酰化是线粒体糖代谢的重要途径。本课题组前期发现SCI后粒细胞集落刺激因子（G-CSF）主要由小胶质细胞分泌，给予锌（Zn2+）可进一步调节神经元线粒体结构和代谢，增加脊髓腹侧运动神经元数量，促进神经运动功能恢复。推测Zn2+通过影响小胶质细胞分泌G-CSF，参与调节SCI后神经元活动。但G-CSF对SCI后神经元细胞作用仍不清楚。因此，本研究拟构建神经元条件性SIRT3过表达和敲除小鼠，观察Zn2+对SCI后神经元代谢变化及线粒体去乙酰化变化的情况。探究Zn2+通过G-CSF/NRF2/SIRT3通路对SCI后神经元线粒体去乙酰化促进SCI神经功能修复的作用。揭示Zn2+促进G-CSF分泌改善神经元线粒体糖代谢治疗SCI的病理机制，为SCI提供新的治疗靶点及方案，具有重要的理论意义和临床应用前景。

Inflammation and mitochondrial metabolism homeostasis play an important role in the recovery of spinal cord injury (SCI). Lysine acetylation / deacetylation is an important pathway for mitochondrial sugar metabolism. We have found that granulocyte colony stimulating factor (G-CSF) is mainly secreted by microglia after SCI. The administration of zinc (Zn2 +) can further regulate the structure and metabolism of neuron mitochondria, increase the number of ventral motor neurons, reduce neurons death and promote the recovery of motor function. It is speculated that Zn2 + may participate in the regulation of neuron activity after SCI through affecting the secretion of G-CSF by microglia. However, the effect of G-CSF on SCI neurons is still unclear. Therefore, this study intends to construct neuronal conditional SIRT3 overexpression and knockout mice. We observed the changes of neuronal metabolism and deacetylation of neurons and mitochondria after SCI by Zn2+. We explored the effect of Zn2 + on the mitochondrial deacetylation of neurons after SCI through G-CSF / NRF2 / SIRT3 signaling pathway to promote the repair of SCI neurological function. The study also reveals the pathological mechanism of Zn2 + promoting G-CSF secretion and improving neuronal mitochondrial sugar metabolism in the treatment of SCI, provides new therapeutic targets and programs for SCI, which has important theoretical significance and clinical application prospects.