Metformin调控脊髓损伤微环境和神经再生的实验研究

脊髓损伤是一种严重的骨科创伤性疾病，在我国发病率逐年升高，损伤后局部微环境改变及内源性神经干细胞激活不足是修复治疗亟待解决的两大难点。最新研究表明，Metformin在神经保护、抗炎、抑制肿瘤生长等方面存在治疗潜力。课题组前期研究结果发现，体外实验中Metformin可以促进神经干细胞增殖及向神经元方向分化，并提高神经源性基因的转录水平；体内实验Metformin可以显著改善损伤局部微环境并增加神经元数量，且不同时间应用药物的修复效果存在差异，但具体机制未明。课题组拟通过体外实验研究Metformin对神经免疫相关细胞和神经干细胞的作用及与相关信号通路的联系；体内实验通过不同时间点注射Metformin的修复效果比较，确定最佳的用药策略，并阐明其调控脊髓损伤微环境和神经再生的病理生理学机制。本课题旨在明确Metformin在脊髓损伤治疗中的新作用及其机制，为临床早期治疗提供可靠依据。

Spinal cord injury is a devastating orthopedic trauma with an increasing incidence in China. The changes of local microenvironment and the insufficient activation of endogenous neural stem cells after injury are the two majar difficulties to be solved in the treatment of spinal cord injury. The therapeutic potential of Metformin in neuroprotection, anti-inflammatory and tumor growth inhibition have been proved in recent studies. Preliminary results of our group shown that Metformin can promote neural stem cells proliferation and induce them to differentiate into neurons in vitro, improve the transcriptional level of neurogenic genes. The application of Metformin can significantly regulate the microenvironment of the lesion site and increase the number of neurons in vivo. The results showed that there were significant differences in the repair effect of starting injection at different time. Our group intends to explore the effect of Metformin on neuroimmune-related cells and neural stem cells and its relationship with relevant signaling pathways through in vitro. The repair effect of starting drug injection at different times will be compared in vivo to determine the optimal medication strategy and to elucidate the pathophysiological mechanism of Metformin regulates microenvironment and neural regeneration following spinal cord injury. In this study, we foucs on clarify the new effect and mechanism of Metformin in spinal cord injury and provide a reliable basis for initial clinical treatment.