脊髓损伤(SCI)后神经细胞发生自噬以及凋亡，其中线粒体自噬以清除受损的线粒体来维持稳态和细胞存活。最新研究发现LC3与Nix结合介导线粒体自噬激活，而LC3与BNIP3结合介导线粒体凋亡反应。前期我们已证实，机械损伤后脊髓神经元自噬被激活并具有保护作用。但脊髓神经元损伤后自噬与凋亡的动态变化过程及机制尚不清楚。据此，我们推测“在损伤早期通过活化Nix介导的线粒体自噬，可能抑制BNIP3通路，防止过度自噬转向凋亡途径，发挥对脊髓神经元的保护作用”。为证实该假说，本课题首先利用细胞模型与动物模型观察脊髓损伤后Nix介导的线粒体自噬与BNIP3介导的线粒体凋亡发生的时间差异与动态变化特点；其次通过早期过表达Nix，和/或抑制BNIP3表达等基因调控技术，优化SCI损伤后的的治疗方案及时机。通过上述研究为将来探索以线粒体自噬为靶标的SCI干预策略和干预时机提供理论依据。

During the process of neuronal autophagy and apoptosis after spinal cord injury (SCI), mitochondrial autophagy is vital to clear the impaired mitochondria and maintain the homeostasis and survival of the cells. Recent studies found that the combination of LC3 and Nix mediates the mitochondrial autophagy, and the combination of LC3 and BNIP3 mediates the activation of mitochondrial apoptosis. In our early research we found that protective autophagy of spinal cord neurons can be activated by mechanical injury. However, the mechanism of autophagy and apoptosis of neurons after SCI is not yet clear. We assume that in the early stage of SCI, activation of Nix mediated mitochondrial autophagy may inhibit the BNIP3 pathway and prevent excessive autophagy that can lead to neuronal apoptosis, and protect the spinal neurons. In order the test this hypothesis, in the current research we will first use the cell and animal models to observe the changes in Nix mediated mitochondrial autophagy and BNIP3 mediated mitochondrial apoptosis after SCI; then by early overexpression of Nix and/or suppressing the expression of BNIP3 using genetic manipulation techniques, attempt to optimize the method and timing of treatment after SCI. This research will provide theoretical basis for future explorations for intervention strategies targeting mitochondrial autophagy after SCI.

细胞主要通过线粒体自噬这一特异性过程及时清除受损的线粒体来维持稳态。已有研究表明，线粒体通透性孔道通透性的改变在这一过程中起重要作用，具体机制不清。最新研究发现脊髓损伤后Nix介导的线粒体自噬被激活。我们本项目研究结果表明，在机械损伤后24小时能诱导线粒体自噬发生，并且其自噬水平随着时间推移，自噬水平不断增强，我们还通过电镜检测出自噬小体结构。同时，我们还通过western blot检测线粒体凋亡相关蛋白，其表达水平随损伤时间有增加趋势。通过本项目研究，我们初步发现，线粒体自噬与凋亡具有一定相关性，然而线粒体自噬与凋亡之间的作用机制尚有待进一步研究。