DCs自噬负向调控NLRP3炎症小体激活介导UC机制及健脾益肠散的调节效应

溃疡性结肠炎(UC)为临床难治病，树突状细胞(DCs)参与了UC肠道黏膜免疫和炎症反应，而DCs自噬调控NLRP3炎症小体激活是免疫反应的重要机制之一。最新研究发现，DCs自噬负向调控NLRP3炎症小体激活介导了UC免疫耐受。课题组前期研究证实，健脾益肠散可调节DCs与炎症因子介导的UC肠道黏膜免疫失衡。因此，本项目提出“健脾益肠散可能通过DCs自噬负向调控NLRP3炎症小体激活途径治疗UC”的科学假说。拟通过在体动物和离体细胞实验，采用高内涵、透射电镜、Western Blot、RT-PCR等技术和方法，从整体-组织-细胞-分子四水平，研究健脾益肠散通过DCs自噬负向调控NLRP3炎症小体激活途径治疗UC的作用机制。进一步证实DCs自噬负向调控NLRP3炎症小体激活介导UC肠道黏膜免疫耐受的分子机制，为健脾益肠散防治UC提供新的思路与靶点，可望在UC的中医药免疫调节治疗中积累更多经验。

Ulcerative colitis (UC) is a clinical refractory disease. Dendritic cells (DCs) participate in the immune and inflammatory response of UC intestinal mucosa, and one of the important mechanisms of immune response is that DCs autophagy regulates the activation of NLRP3 inflammatory bodies. Recently, it has been found that DCs autophagy negatively regulates the activation of NLRP3 inflammatory bodies and mediates the immune tolerance of UC. The previous study of the research group confirmed that Jianpi Yichang powder can regulate the imbalance of intestinal mucosal immunity mediated by DCs and inflammatory factors in UC. Therefore, this project puts forward the scientific hypothesis that "Jianpi Yichang powder may treat UC through DCs autophagy negative regulation of NLRP3 inflammatory body activation pathway". Through in vivo and in vitro cell experiments, using high connotation, transmission electron microscopy, Western blot, RT-PCR and other technologies and methods, from the whole tissue cell molecule level, to study the mechanism of Jianpi Yichang powder in the treatment of UC through DCs autophagy negative regulation of NLRP3 inflammatory body activation pathway. It is further confirmed that DCs autophagy negatively regulates the activation of NLRP3 inflammatory bodies and mediates the molecular mechanism of UC intestinal mucosal immune tolerance, which provides a new idea and target for the prevention and treatment of UC with Jianpi Yichang powder, and is expected to accumulate more experience in the immunomodulatory treatment of UC with traditional Chinese medicine.