NF-κB相关miRNA筛选及下游NLRP3活化促进胆道炎症参与胆道结石形成机制及大黄灵仙胶囊的干预效应研究

持续性胆管细胞炎性损伤触发的胆道病理性重塑是胆道结石反复发作难以解决的关键问题。新近发现，NLRP3活化是炎症应激得以强化和迁延的关键调节子；已证实大黄灵仙胶囊临床防治胆石症疗效确切，前期研究发现该方缓解胆管细胞炎性应激，调控多个与NF-κB信号通路相关的miRNAs表达。基于此，项目组提出大黄灵仙胶囊可能通过调控miRNAs表达影响NF-κB信号通路拮抗下游NLRP3炎症小体活化缓解胆管细胞炎性损伤阻断胆道结石形成的疗效机制假说。项目拟通过复制胆管细胞炎症模型及大鼠胆道炎症损伤模型，大黄灵仙胶囊干预处理，使用多种研究手段，从分子、细胞、动物层面探明大黄灵仙胶囊通过miRNAs/NF-κB信号通路途径拮抗NLRP3炎症小体活化缓解胆管细胞炎性损伤阻断胆道结石形成的分子机制。解析大黄灵仙胶囊拮抗胆管炎性进程、缓解胆道结石形成的科学内涵，为中医药治疗胆道结石拓宽思路并为其提供科学支撑。

The pathological remodeling of the bile duct triggered by the persistent inflammatory injury of bile duct cells is a key problem that can not be solved in the repeated onset of cholelithiasis. Recently, it has been found that NLRP3 activation is the key regulator for the enhancement and prolongation of inflammatory stress. It has been confirmed that Dahuanglingxian capsules has a clear clinical effect in the prevention and treatment of cholelithiasis. Previous studies have found that this formula can alleviate the inflammatory stress of bile duct cells and regulate multiple miRNAs related to NF-κB signaling pathway. Based on this, the project team proposed the hypothesis that Dahuanglingxian capsules may affect the NF-κB signal pathway by regulating the expression of miRNAs to inhibit the activation of downstream NLRP3 inflammatory bodies to alleviate the inflammatory injury of bile duct cells and block the formation of bile duct stones. In this project, we intend to use a variety of research methods to explore the molecular mechanism of Dahuanglingxian capsules blocking the formation of cholelithiasis through the miRNAs/NF-κB signal pathway through the activation of NLRP3 inflammatory small body to alleviate the inflammatory injury of bile duct cells and the formation of bile duct stones. To analyze the scientific connotation of Dahuanglingxian capsules in antagonizing the process of cholangitis and relieving the formation of cholelithiasis, so as to provide scientific basis for the treatment of cholelithiasis with traditional Chinese medicine.