克罗恩病(CD)属炎症性肠病,是世界公认的疑难病症,国内发病率日趋上升,艾灸治疗轻中型CD疗效确切。研究证实NLRP3炎症小体与CD发病关系密切。基于前期研究成果,本项目以NLRP3炎症小体及其上下游信号通路为切入点,探讨NLRP3/ASC/caspase-1通路与CD发生发展的关系及艾灸的干预作用;并观察艾灸对ATP/P2X7R、ROS、cathepsin B炎症小体正调控途径的调节作用,探讨线粒体自噬/NLRP3炎症小体在肠黏膜上皮细胞的变化与艾灸的干预效应,拟证实NLRP3/ASC/caspase-1通路与CD发生发展密切相关,艾灸通过调节CD肠黏膜NLRP3/ASC/caspase-1上游正调控途径(P2X7R、ROS、cathepsin B)和线粒体自噬负调控途径,抑制NLRP3炎症小体过度活化,进而减少肠黏膜IL-1β和IL-18过度表达,达到减轻肠道炎症、恢复肠道稳态之目的。

As a kind of inflammatory bowel disease, Crohn’s disease (CD) has been universally considered an intractable disease and its incidence has been increasing in China. It’s been confirmed that moxibustion is effective in treating mild-to-moderate CD. NLRP3 inflammasome has been revealed closely related to the pathogenesis of CD. Based on the previous work, targeting NLRP3 inflammasome and its upstream and downstream signaling pathways, this study was to discuss the relationship between the NLRP3/ASC/caspase-1 signaling pathway and the development of CD, as well as the intervention effect of moxibustion; also to observe the regulatory effect of moxibustion on the positive control elements P2X7R, ROS, and cathepsin B, and explore the change of mitophagy/NLRP3 inflammasome in intestinal mucosal epithelial cells and the intervention of moxibustion, for proving that the NLRP3/ASC/caspase-1 signaling pathway is closely related to the development of CD, and moxibustion reduces intestinal inflammation and restores intestinal homeostasis via regulating the upstream positive control molecules P2X7R, ROS, and cathepsin B of NLRP3/ASC/caspase-1 and the negative control of mitophagy in colonic mucosa, inhibiting the hyperactivation of NLRP3 inflammasome, and down-regulating the hyper-expression of IL-1β and IL-18 in intestinal mucosa.