MicroRNAs在溃疡性结肠炎发生发展过程中发挥重要作用。课题组前期研究已证实柠檬苦素可显著改善溃疡性结肠炎（UC）动物模型的肠道炎症，但其作用机制不明确。本课题组进一步研究发现柠檬苦素能够显著下调miR-214和STAT3磷酸化表达水平，反向上调靶基因PTEN和PDLIM2表达水平进而抑制NF-kB等促炎因子的释放。本项目提出柠檬苦素可能通过介导IL-6/STAT3信号通路调控miRNA-214及其靶基因PTEN和PDLIM2抑制下游AKT、NF-κB信号通路以及炎症因子过度表达，修复肠道粘膜并改善肠道炎症。为此，本项目拟采用免疫共沉淀、基因编辑技术、基因敲除以及免疫组化等方法，在细胞和动物水平并结合临床样本进行研究柠檬苦素对miRNA-214及靶基因PTEN和PDLIM2的调控网络的作用，深入阐明柠檬苦素抑制UC的作用机制，为中医药治疗UC以及中药新药评价提供新的思路和依据。

MicroRNAs play an important role on the occurrence and development of disease Ulcerative colitis (UC). Previous studies have demonstrated that limonin plays a critical role in the treatment of UC. But its exact mechanism has not been clarified. Limonin is highly distributed in different parts of the intestinal tissue, although only a small amount of drug was absorbed into the blood. The anti-inflammatory action of limonin is by inhibiting IL-17 and NF-κB cytokine, downstream effectors of miR-214 and STAT3 phosphorylation, up-regulation of PTEN and PDLIM2 in the treatment of UC. This project is to establish the UC animal model and explore the regulatory mechanism of limonin in the treatment of Ulcerative colitis based on IL-6/STAT3 signaling pathways by regulating miRNA-214 and the target gene PTEN and PDLIM2. Co-Immunoprecipitation, gene knockout and genome editing technique were employed to study the effect of limonin on miRNA-214 and target gene PTEN and PDLIM2 in order to discuss the mechanisms of limonin treating UC base on the cellular and animal levels and combined with clinical samples. The result will provide new ideas and evidences for looking for new drugs in TCM and the rational drug use in UC clinic treatments.