NF-κB/TREM2介导的小胶质细胞M1/M2极化在Morin缓解长春新碱所致神经病理性疼痛中的作用机制研究

长春新碱是化疗的传统药物，但神经病理性疼痛并发症严重限制其在临床上的应用，因此迫切需要能有效缓解该副作用的药物。课题组既往研究证实，Morin能抑制NF-κB，减少促炎因子，缓解长春新碱所致的神经病理性疼痛，但机制不清；前期研究发现小胶质细胞M1/M2极化转变与Morin缓解长春新碱所致神经病理性疼痛有关，调控NF-κB可改变小胶质细胞M1/M2极化，但分子机制仍不清；TREM2是调控小胶质细胞活化状态的重要信号蛋白且具有两个NF-κB结合位点，因此推测调控NF-κB/TREM2，促进小胶质细胞M1向M2转化可能是Morin缓解长春新碱所致神经病理性疼痛的机制。本项目拟在动物和细胞水平，通过基因过表达，基因干扰和敲除等方法探讨NF-κB/TREM2介导的小胶质细胞M1/M2极化在Morin缓解长春新碱所致神经病理性疼痛中的作用机制，以期为长春新碱所致神经病理性疼痛的预防和治疗提供新的靶点。

Vincristine is a traditional drug of chemotherapy, but its clinical application is severely limited by the complications of neuropathic pain,so it is urgent to find a drug that can effectively alleviate the side effects. Our previous study shown that Morin can inhabit NF-κB, reduce the release of pro-inflammatory factors and then alleviate the neuropathic pain significantly induced by Vincristine, but the mechanism is not clear. Our preliminary studies have found that the M1/M2 polarization of microglia is related to Morin alleviating neuropathic pain caused by Vincristine, regulation of NF-κB can change the M1/M2 polarization of microglia, but the molecular mechanism is unclear. TREM2 is an important signal protein regulating the activation of microglia and has two NF-κB binding sites. Therefore we speculate that regulating NF-κB/TREM2 to promote the M1/M2 polarization of microglia may be the mechanism of Morin alleviating the neuropathic pain caused by Vincristine. This project is to explore the mechanism of M1/M2 polarization of microglia mediated by NF-κB/TREM2 on Morin reliving neuropathic pain caused by vincristine via gene overexpression, gene interference and knock out, in order to provide a new direction for the prevention and treatment of neuropathic pain caused by Vincristine.