长链非编码RNA SPRY4-IT1抑制血清素表达抗肠上皮损伤的分子机制研究及在肠屏障损伤模型的应用

Our previous study indicated that probiotics and its active component may contribute to the maintenance of the normal structure and function of intestinal epithelial tight junction, which involved in the molecular mechanism of miRNA-21 and zonulin. It is newly found that long noncoding RNA SPRY4-IT1 could regulate the expression of tight junction, and serotonin might also play a role in the injury of intestinal epithelium. On the basis of our previous study, we now put forward the hypothesis that SPRY4-IT1 may protect the intestinal epithelial from injury by inhibiting the expression of serotonin, the molecular mechanism of which will be verified from three levels, such as cell, mouse, and human samples. The transgene mouse which our previous constructed and the sample of human obstruction will be used as well. Furthermore, we aim to construct a model for the molecular diagnosis of intestinal barrier injury, which will also be verified by different mouse models and human sample. Fecal transplantation is a new and hot technique recent years, which also be used in the verification. If our study got the expected results, the first molecular diagnostic model of intestinal barrier injury will be constructed, which will promote the diagnostic study of intestinal barrier dysfunction, and further investigate the molecular mechanism of intestinal barrier dysfunction through the aspect of long noncoding RNA, with great clinical significance.

本课题组前期研究发现益生菌及其活性成分可以维持肠上皮紧密连接的正常结构和功能，其分子机制与miRNA-21，zonulin等有关。最新研究表明长链非编码RNA SPRY4-IT1对紧密连接蛋白具有调控功能，另有研究示血清素在肠上皮损伤过程中起着重要作用。本课题在此基础上提出假说——SPRY4-IT1可能抑制血清素的表达发挥其抗肠上皮损伤作用，并通过细胞-动物-临床标本等不同水平进一步探讨其作用的分子机制，通过前期建立的转基因小鼠以及临床肠梗阻标本进行验证。在此基础上结合课题组前期发现的相关标志物进一步建立肠屏障损伤的分子诊断模型，最后通过动物实验及临床标本进行验证。此外，我们将粪菌移植应用于临床标本的研究中，具有创新性。本课题如能取得预期成果，将首次提出并建立肠屏障损伤分子诊断模型，推动肠屏障功能障碍诊断的研究进展，并进一步从长链非编码RNA角度探讨肠屏障损伤的分子机制，具有重要临床意义。

本课题在前期研究发现益生菌及其活性成分可以维持肠上皮紧密连接的正常结构和功能的基础上，结合其分子机制与miRNA-21，zonulin，以及国外最新研究长链非编码RNA SPRY4-IT1对紧密连接蛋白的调控功能，提出提出假说——SPRY4-IT1可能抑制血清素的表达发挥其抗肠上皮损伤作用，并通过细胞-动物-临床标本等不同水平进一步探讨其作用的分子机制，通过前期建立的转基因小鼠以及临床肠梗阻标本进行验证。并针对粪菌移植展开相关研究。首次提出并建立肠屏障损伤分子诊断模型，推动肠屏障功能障碍诊断的研究进展，并进一步从长链非编码RNA角度探讨肠屏障损伤的分子机制，具有重要临床意义。研究工作进展顺利，基本按照原工作计划完成。本研究团队共发表论文13篇，其中SCI论文11篇。申请专利3项，其中发明专利2项，实用新型1项。