溃疡性结肠炎（UC）详细发病机制不明，常规治疗不能改变潜在免疫紊乱，因此本病难治愈易复发。本项目组前期成功研制五味苦参肠溶胶囊，实现口服结肠定位释药，临床试验显示等效于柳氮磺吡啶片和不劣于美沙拉秦缓释颗粒，复发率低，获国家新药证书（国药准字Z20150002）；已完成动物实验证实该药能显著减低UC小鼠肠粘膜IL-1β、IL-17表达，抑制免疫炎症反应。因此为进一步明确该药物作用机制，本项目组拟从临床、动物、细胞多层面观察该药物对UC肠粘膜NLRP3炎性小体活化及IL-1β的影响，通过对IL-17生成细胞(ILC17、TH17)亚群鉴定，探讨炎症因子IL-1β与IL-17生成细胞(ILC17、TH17)的关联机制，验证“五味苦参肠溶胶囊通过抑制NLRP3炎性小体生成IL-1β，抑制IL-17生成细胞表达IL-17“的假说，对揭示UC发生规律、寻求新的治疗靶点、进一步中药优化筛选具有重要意义。

The exact pathogenesis of ulcerative colitis (UC) is unknown, and conventional therapies can not change the underlying immune dysfunc-tion, the disease becomes difficult to cure but easy to relapse. The project team successfully invented Wuwei Kushen enteric capsules using the technic of oral colon-specific drug delivery system to achieve the colon topical administration. And we finished two clinical trials which showed the therapeutic effect of Wuwei Kushen enteric capsules was equivalent to sulfasalazine tablets and not inferior to mesalazine slow-release particles with low recurrence rate. The achievement won the national new drug certificate(Drug Identification Number:Z20150002). We also finished series of animal experiments, indicated that the drug could significantly inhibit the immune inflammatory reaction in intestinal mucosa of UC mice via reducing IL-1β and IL-17 expression. Therefore to investigate the drug mechanism is quite necessary, the project team intend to conduct series experiments in clinical, animal and cell levels to observe the effects of the drug on intestinal mucosa NLRP3 inflammasome and IL-1β expression in UC mice, identify the IL-17-producing cells (ILC17, Th17) subgroup, investigate the interaction mechanism of inflammatory cytokines IL-1β,IL-17 and IL-17-producing cells (ILC17, Th17), to prove if ‘Wuwei Kushen enteric capsules could inhibit the process of NLRP3 inflammasome promoting IL-1β generation, thus restain IL-17-producing cells to express IL-17’.This project would be of great significance for revealing pathogenesis of UC, searching new therapeutic targets and further optimization of traditional Chinese medicine compound.