肠道纤维化是克罗恩病（CD）常见的严重并发症，但目前没有能够特异性抑制肠道纤维化的药物。研究证实TGF-β及其下游Smads和MAPK信号通路可能通过介导上皮间质转化（EMT）参与并促进了肠道的纤维化形成。课题组前期研究证实黄蜀葵花的主要成分-黄蜀葵花总黄酮（TFA）通过干预MAPK/NF-κB信号通路，抑制促炎因子TNF-α、INF-γ的过度释放来减轻CD肠道炎症，降低模型动物结肠组织中TGF-β、α-SMA和MMP-2等纤维化标志，减轻CD模型小鼠肠道纤维组织增生。本研究拟通过在体模型、细胞水平研究调控TGF-β及其下游Smads和MAPK信号通路介导EMT进程的机制，阐明EMT在CD肠纤维化过程中的作用及调控机制；并通过分析EMT进程中关键信号通路与分子变化，明确TFA抑制/逆转肠纤维化的作用和可能机制，进一步深化研究黄蜀葵花效用机制，为开发治疗CD肠纤维化的新型中药提供依据。

Intestinal fibrosis is a common and serious complication of the Crohn’s disease. Currently, no specific medical therapy exists to treat fibrotic intestinal strictures. It has been proved that epithelial-mesenchymal transition (EMT) affair is one of the critical steps during the development of intestinal fibrosis. TGF-β, activated Smads transcription factors and MAP kinase signaling pathways may be involved in the process of EMT and improved the forming of intestinal fibrosis. The experiments performed by our group have confirmed that total flavone of Abelmoschus manihot (L.) Medicus (TFA) can inhibit intestinal fibrosis in the TNBS-induced model of CD. The mechanism of this is related to activated MAPK/NF-κB signaling pathway, relieving intestinal inflammation by inhibitation TNF-α、INF-γ, and improving intestinal fibrosis by decreasing TGF-β、α-SMA和MMP-2. The aim of this study is to elaborate the molecular mechanisms of EMT in forming intestinal fibrosis in vivo and in vitro, with special signaling pathways related to EMT, such as TGF-β、Smads and MAPK. On this basis, we will explore the effect and molecular mechanisms of TFA on EMA that inhibit or reverse intestinal fibrosis in Crohn’s disease. This study will be not only an endeavor to look for new target and drug for the treatment of intestinal fibrosis of crohn’s disease, but also a new exploration on the effective component of Chinese medicine.