普拉梭菌经PI3K-MAPK通路调控Syndecan-1在溃疡性结肠炎中的保护作用研究

溃疡性结肠炎（UC）因其治疗费用昂贵、复发率高而受到广泛关注和重视。UC患者常伴有普拉梭菌下降，但迄今为止，有关UC中普拉梭菌抗炎调控机制研究仍很缺乏。我们前期发现UC病情严重度与Syndecan-1（Sdc1）表达减少相关，而普拉梭菌有效缓解因Sdc1破坏而诱发的肠道炎症损伤。然而普拉梭菌是否参与Sdc1调控、如何调控等关键问题均未解决。本项目以临床UC患者为切入点，构建细胞炎症模型和DSS诱导小鼠UC模型，通过普拉梭菌干预，RNA干扰技术、信号通路阻滞、屏障功能检测等方法研究普拉梭菌抗炎调控机制：普拉梭菌和Sdc1与肠屏障功能的关系与规律性；普拉梭菌-PI3K/MAPK通路-Sdc1三者调控关系与规律性。探索“普拉梭菌经PI3K/MAPK通路调控Sdc1，进而改善/逆转肠道炎症损伤及肠屏障功能、阻止UC进程”的科学问题，为普拉梭菌抗炎调控机制提供新理论，为UC的防治奠定理论和实验基础。

Ulcerative colitis(UC) has received extensive attention due to high cost of treatment and recurrence rate. Reduced faecalibacterium praunitzii is common in UC. However, there is still a lack of studies concerning anti-inflammatory mechanism of faecalibacterium praunitzii in UC. In our preliminary study, a notable interconnection was observed between UC severity and Syndecan-1 (Sdc1) destruction and F.prausnitzii could alleviate the intestinal inflammation resulted by the Sdc1 destruction in mice. But unfortunately, the mechanisms for the anti-inflammatory effect of faecalibacterium praunitzii remain unknown. The core issues, including whether or how faecalibacterium praunitzii participate in Sdc1 regulation are still being explored. In this proposal, the project will be performed in UC patients, DSS-induced UC animal model and cell-inflammatory model to study the anti-inflammatory mechanism of faecalibacterium praunitzii via Sdc1 gene silencing by RNA interference, inhibition of PI3K-MAPK signaling pathways, establishment and monitoring intestinal barrier etc.,to expore the anti-inflammatory mechanism of faecalibacterium praunitzii. The association between faecalibacterium praunitzii, Sdc1 and gut barrier function will be comprehensively studied. The association between faecalibacterium praunitzii, PI3K/MAPK signaling pathways and Sdc1 will be also comprehensively expored. We will suppose that faecalibacterium praunitzii regulate Sdc1 via PI3K/Akt and MAPK/ERK (PI3K-MAPK) signaling pathways, and subsequently reduce inflammatory reaction, reverse the impaired intestinal barrier and prevent UC progress. This will provide new theories for anti-inflammatory effect of faecalibacterium praunitzii and lay the theoretical and experimental basis for UC treatment.