基于TNFR2信号调控脊髓Treg功能探讨电针治疗慢性疼痛的机制研究

调节性T细胞（Treg）可抑制脊髓炎症反应和痛觉敏化，在慢性疼痛恢复中不可或缺。近期研究发现，Treg上的肿瘤坏死因子受体Ⅱ信号(TNFR2)激活是维持免疫平衡，调控疼痛的关键信号分子。本人预实验发现，电针干预后，慢性疼痛模型动物脊髓中Foxp3(Treg标志性转录因子)和TNFR2蛋白的表达均上调，但具体机制不清。我们推测，脊髓Treg上的TNFR2，可能是电针治疗慢性疼痛的效应靶点。本研究拟在慢性疼痛小鼠模型上，通过TNFR2阻断、Treg耗竭和Treg过继转移手段，使用蛋白组学、转录组学和流式细胞学等方法，从分子-信号通路-细胞-动物多个层次来解析电针激活脊髓TNFR2及其下游通路在促进Treg功能、维持免疫平衡、缓解神经炎症和促进慢性疼痛恢复的分子机制。本项目将阐明电针镇痛效应新机制，丰富针刺调节“阴阳平衡”的科学内涵，具有重要的理论意义和应用价值。

Regulatory T cells (Treg) inhibit spinal cord inflammation and pain sensitization and are indispensable in chronic pain recovery. Recently, researchers found that the signal activation of the tumor necrosis factor receptor Ⅱ(TNFR2) on Treg is pivotal to control pain signaling molecules and maintain immunity homeostasis. My preliminary experiment found that after electroacupuncture intervention, the protein expression of Foxp3 (signature transcription factors of Treg) and TNFR2 were both upregulated at the spinal cord region of chronic pain model animals, but the specific mechanism was unclear. We speculated that TNFR2 in the spinal cord Tregs may be a potential target of electroacupuncture analgesia. Studies in this project were conducted on the chronic pain model in mice, by TNFR2 blocking, Treg depletion, and Treg adoptive transfer, using proteomics, transcriptome, and methods of fluid cytology, from molecular signaling pathways – cell - including animal multi-level perspective to elucidate the activation of TNFR2 and their downstream channel in promoting Treg at the spinal cord function, to maintain the immune balance, alleviate nerve inflammation and promote the molecular mechanism of chronic pain recovery. This project will clarify the new mechanism of the electroacupuncture analgesia effect and enrich the scientific connotation of acupuncture regulation of "balance of Yin and Yang", which has important theoretical significance and application value.