GSDMD细胞焦亡途径调控“疾病相关小胶质细胞(DAM)”表型介导针刺促进髓鞘修复的效应机制

促进髓鞘修复再生是治疗多发性硬化（MS）等脱髓鞘疾病的重要途径，目前缺乏有效治疗手段。小胶质细胞活化是脱髓鞘病理损伤及影响髓鞘再生的重要机制，我们前期研究发现电针通过调控小胶质细胞活化促进髓鞘修复，2017年科学家利用单细胞测序ScRNA-seq技术发现了一类具有神经保护功能的疾病相关小胶质细胞（Disease-associated microglia,DAM）亚型，课题组前期转录组分析发现电针可以上调与DAM表型相关的特征分子，但具体机制不明。本课题拟从局部损伤微环境影响小胶质细胞活化分型着手，采用Cuprizone诱导脱髓鞘模型，观察小胶质细胞细胞焦亡对局部微环境的影响，综合应用ScRNA-seq、形态学、分子及细胞生物学等多种技术手段，阐明GSDMD细胞焦亡通路调控DAM表型的分子机制及其在电针促进髓鞘修复中的作用，为针刺应用于MS等脱髓鞘疾病的临床治疗提供新的思路及理论依据。

Promoting remyelination is an important way to treat demyelinating diseases such as multiple sclerosis (MS), but there is no effective treatment at present. Microglia activation plays an important role underlies demyelinating pathological damage and remyelination. Our previous research demonstrated that electroacupuncture can effectively promote remyelination by regulating microglia activation. In 2017, scientists discovered a class of disease-associated microglia (DAM) subtype which has a neuroprotective function by using single cell sequencing (ScRNA-seq) technology, transcriptome analysis showed that electroacupuncture can upregulate the characteristic molecules related to DAM phenotype, but the specific mechanism is unknown. In this study, we intend to focus on the effect of local injury microenvironment on microglia activation and polarization, by using the cuprizone-induced demyelination model, investigate the effect of microglia pyroptosis on the local microenvironment, and comprehensively use various methology such as ScRNA-seq, morphology, molecular and cell biology to clarify the molecular mechanism of the GSDMD pyroptosis pathway regulating the microglia DAM phenotype and pro-remyelination effect of electroacupuncture, and provides new ideas and theoretical basis for the clinical application of acupuncture for demyelinating diseases such as MS.