肠上皮细胞来源的外泌体介导炎症信息的传递在重症急性胰腺炎肠屏障损伤中的作用及机制研究

研究表明外泌体与肠上皮细胞（IEC）炎症反应密切相关，但IEC来源的外泌体在重症急性胰腺炎（SAP）肠屏障损伤中的作用未见报道。我们前期在SAP小鼠的粪便中发现了IEC来源的外泌体；且其可引起肠巨噬细胞（IM）炎症反应；我们用高通量测序技术对其进行分析，发现其内含有多种炎症相关miRNAs。故我们假设SAP诱导的IEC来源的外泌体，通过向IM传递miRNAs，介导了IEC与IM间炎症信息的传递，导致肠内炎症介质失控性释放，是SAP肠屏障损伤的重要环节。本项目拟观察SAP时IEC来源外泌体的分泌情况；体内外实验抑制SAP诱导的IEC外泌体的分泌，观察其对减轻IM炎症反应的效果及对SAP肠屏障损伤的保护作用；并采用基因芯片结合前期miRNAs测序结果，筛选出外泌体中导致IM炎症反应的关键miRNAs及其靶基因，揭示外泌体介导IEC与IM间炎症信息的传递方式，探讨其促进SAP肠屏障损伤的机制。

Previous studies have shown that exosomes are closely related to intestinal inflammatory response in intestinal epithelial cells (IEC), but the role of IEC-derived exosomes in intestinal barrier damage in severe acute pancreatitis (SAP) has not been reported. In our initial study We have found IEC-derived exosomes in the feces of SAP mice which can cause inflammatory response in intestinal macrophage (IM). Then IEC-derived exosomes were analyzed with high-throughput miRNA sequencing technology, which contains multiple inflammatory-related miRNAs. Therefore, we hypothesized that SAP induced IEC-derived exosomes, through the delivery of miRNAs to IM, mediate the transmission of inflammatory information between IEC and IM, leading to the uncontrolled release of intestinal inflammatory mediators, which is an important link in the intestinal barrier damage of SAP. Our study is to observe the secretion of IEC-derived exosomes from SAP; the in vitro and in vivo experiments inhibit the secretion of IEC exosomes induced by SAP, observe its effect on reducing IM inflammatory response and protect the intestinal barrier of SAP; The results of gene chip combined with the sequencing of miRNAs screened out key miRNAs and their target genes in exosomes leading to IM inflammatory response,Revealing the transmission of inflammatory information between IEC and IM mediated by exosomes, and explore the mechanism of promoting intestinal barrier damage in SAP.