血清反应因子（SRF）通过“Ras-Raf-cofilin”信号通路促进脊髓损伤后神经元轴突再生的分子机制研究

Spinal cord injury (SCI) is a clinical common disease, and the therapies for SCI have been limited due to low intrinsic regenerative capacity of injured central neurons. So how to improve the regenerative capacity of neuron, inhibitory extrinsic environment is the key factors in treat spinal cord injury. Some previous study showed that SRF have an important effect in neurons, it can promote the regeneration of neurons, and improve the environment for nerve regeneration, but there has been rarely reported in spinal cord injury research. In our previous research, we found that SRF was neuron-specific expression in different injury periods and the quantity was significantly up-regulated in SCI rats. In order to research whether SRF can promote SCI recovering and the mechanisms, we over-express and down-regulate SRF levels in spinal cord injury rat and spinal cord neurons, then detect the function by BBB score, immunostaining test, electron microscope observation and electrophysiological experiment.

脊髓损伤是临床常见的高致残率疾病，由于神经元内在再生能力有限，常规的修复治疗很难实现神经再生。如何有效提高神经元的内在生长能力和改善受损神经元的再生微环境成为治疗脊髓损伤的关键。SRF可以在调整面神经元细胞骨架动力学的同时介导立即早期基因反应，改变神经损伤后的微环境，促进轴突再生，但其在脊髓损伤中的作用及具体机制不清楚。我们的前期研究发现，脊髓损伤后SRF可在脊髓灰质神经元样细胞中表达，其表达量较正常脊髓持续增高，在损伤后第7天达到高峰，损伤后28天趋于正常，提示SRF可能参与脊髓损伤的修复过程。本研究拟通过转基因鼠和基因转染技术，从离体和在体两方面分析SRF在脊髓损伤中的作用，并探索神经元轴突再生和修复的新机制，为脊髓损伤相关药物开发提供实验依据和新思路。

脊髓损伤是临床常见的高致残率疾病，由于神经元内在再生能力有限，常规的修复治疗很难实现神经再生。如何有效提高神经元的内在生长能力和改善受损神经元的再生微环境成为治疗脊髓损伤的关键。本项目从离体和在体两方面首次分析血清反应因子（SRF）在脊髓损伤中的作用，并探索神经元轴突再生和修复的可能机制。本研究分别制造大鼠脊髓损伤模型和神经元损伤划痕模型，通过免疫荧光、WB、RT-PCR、Elisa等实验方法检测损伤后不同时间点SRF的表达水平，并对损伤后轴突的再生情况、髓鞘再生情况、部分因子的表达情况进行观察，同时过表达或沉默SRF的表达，进一步验证SRF的作用及可能机制。结果显示，SRF在脊髓损伤后的表达增高，达到高峰后逐渐趋于正常水平；SRF的表达水平降低时轴突再生能力减弱，神经元迁移能力减弱，神经元凋亡增加；SRF的表达水平增高时神经元迁移能力增强；SRF的表达与Ras，Raf，Cofilin的表达趋势一致。我们推测SRF可以促进神经元轴突的再生，且是通过“Ras-Raf-cofilin”信号通路发挥作用。SRF可以作为脊髓损伤后治疗的新型药物和治疗靶点。