补体攻膜复合物（MAC）在溃疡性结肠炎（UC）中的作用尚缺乏直接研究证据。我们在DSS诱导的UC模型中发现，C9基因敲除导致MAC缺失后小鼠UC损伤明显减轻，IL-1β等因子水平和中性粒及巨噬细胞浸润明显降低，且MAC主要显著沉积于结肠上皮细胞（CEC），提示MAC可能通过介导CEC损伤促发UC，但其作用和机制仍待探讨。转录组分析证实，MAC缺失后结肠组织中NLRP3/IL-1β相关的炎症介质以及ERK1/2（NF-κB候选）为代表的信号转导发生显著变化，为我们深入研究MAC在UC中的作用和机制提供了重要方向。本项目将联合生物信息学、免疫学、分子与细胞生物学等方法，通过体内外实验确认MAC介导的CEC损伤在促发UC中的贡献，探讨MAC在CEC内激发的信号转导机制及对NLRP3/IL-1β炎症通路的调控作用，以期从新的角度揭示UC的发病机制，为临床治疗UC提供新的特异性靶点。

Involvement of the complement system in the development of ulcerative colitis (UC) has been suggested, however the role of complement membrane attack complex (MAC) in triggering UC is still indefinite. In the preliminary data, we proved that MAC deficiency mice due to C9 gene knockout(C9-/-) showed decreased colitis damage and neutrophil and macrophage infiltration than WT mice. We further confirmed that MAC mainly deposited on colonic epithelial cells (CECs), which suggesting MAC may aggravate UC by triggering CEC injury. Yet the mechanisms by which MAC mediates CEC injury still need to be investigated. Transcriptome sequencing analysis indicated that membrane disruption, NLRP3/IL-1β associated inflammatory mediators and inflammatory associated signaling pathways especially ERK1/2 signaling were significantly affected in the absence of MAC formation, which clearly directed our hypothesis that MAC may induce NLRP3/IL-1 axis through evoking inflammatory associated signaling pathways (especially ERK1/2, and NF-κB in candidate). In the present research, by integrating bioinformatic, immunological, molecular and cell biological methods, we aim to confirm the contribution of MAC on CEC injury during UC development, to investigate the signal transduction mechanisms of MAC in CEC, and to reveal their effects in regulating NLRP3/IL-1β axis through both in vivo and in vitro experiments. We hope our finding will be helpful to reveal the pathogenesis of UC from a new perspective angle and to provide novel specific targets for clinical treatment of UC.