基于miR-141-3p/Notch/Nrf2介导的神经元自噬-铁死亡crosstalk探讨补肾活血方治疗脊髓损伤的作用机制

脊髓损伤是严重的中枢神经系统创伤，而脊髓运动神经元程序性死亡严重阻碍神经功能修复。自噬与铁死亡是该过程中维持机体内环境稳定的重要因素，且二者协同调控、交叉串话。研究表明Notch-Nrf2轴与脊髓损伤后细胞保护的调控机制息息相关，而miR-141-3p可通过激活Notch/Nrf2轴调控自噬-铁死亡crosstalk；补肾活血方能有效促进功能障碍的恢复，减轻脊髓病理损伤，且miR-141-3p可能是补肾活血方发挥作用的关键分子，但其具体作用靶点尚不明确。本课题拟从细胞、动物、分子三个层面，通过基因芯片测序、荧光素酶报告基因、慢病毒感染、免疫共沉淀等技术阐明miR-141-3p/Notch/Nrf2介导自噬-铁死亡crosstalk的具体分子机制，并以此为切入点探讨补肾活血方干预脊髓损伤的作用靶点，为揭示脊髓损伤的病机研究提供了崭新视角，也为后续更多潜在药物的研发开拓了思路。

Spinal cord injury is one of the most serious injuries in central nervous system, and the programmed death of spinal cord motor neurons severely hinders the repair of neural function. Autophagy and ferroptosis are important factors to maintain the stability of the body’s internal environment in this process, and the two interact coordinately and crosstalk with each other. Studies have demonstrated that the Notch-Nrf2 axis is closely related to the regulatory mechanism of cytoprotection after spinal cord injury, and miR-141-3p may regulate the crosstalk between autophagy and ferroptosis through activating the Notch/ NRF2 axis. Bushen Huoxue Decoction can effectively promote the recovery of dysfunction and alleviate the pathological injury of the spinal cord. Moreover, we considered that miR-141-3p may be the key regulator of Bushen Huoxue Decoction, but its specific target is still unclear. Therefore, in this project, by using a series of experimental methods including gene chip sequencing, luciferase reporter gene, lentivirus infection and immunoprecipitation, we try to clarify the specific molecular mechanism of miR-141-3p/Notch/NRF2 in regulating autophagy-ferroptosis crosstalk. And takes this as the entry point to discuss the pharmacological pathway and targets of Bushen Huoxue Decoction in the treatment of spinal cord injury, which provides a new perspective to reveal the pathogenesis of spinal cord injury, and also opens up ideas for the subsequent development of more potential drugs.