基于TGR5/GLP-2信号通路研究原花青素调控断奶仔猪肠道屏障功能及炎症的分子机制

维护肠道健康是缓解仔猪断奶应激的关键，而针对仔猪肠道健康的靶向调控手段极其缺乏。TGR5是重要的胆汁酸膜受体，它介导的信号通路参与调控细胞炎症反应及屏障功能。近期研究表明，天然植物多酚原花青素(PAC)可提高动物肠道GLP-1基因表达,而GLP-1是TGR5激活的标志之一。我们已发表文章报道：TGR5激活剂可刺激仔猪GLP-2分泌。而GLP-2有改善肠道屏障功能及炎症的作用。由此推测，PAC或许能通过TGR5/GLP-2信号通路调控仔猪肠道健康。本项目通过实施静脉插管手术并构建免疫应激模型揭示PAC调控断奶仔猪肠道炎症及屏障功能的作用依赖于TGR5/GLP-2。再进一步使用肠道内分泌细胞进行研究，明确PAC激活TGR5，促进GLP-2分泌的作用机制。本项目旨在阐明PAC调控断奶仔猪肠道炎症及屏障功能的分子机制，探究仔猪肠道健康调控的新靶标,为断奶仔猪肠道健康的营养调控提供新视角。

Maintaining the gut health of weaned piglets is critical in alleviating weaning stress of piglets. However, strategies targeted at modulating gut health of piglets are extremely scarce. TGR5, an important membrane receptor of bile acids, has been reported to play pivotal roles in regulation of cellular inflammtion and barrier function through mediating its downstream signaling molecules. In recent study, proanthocyanidin (PAC), natural plant polyphenol, has been proven to be capable of enhancing the intestinal gene expression of GLP-1, which is one of the key makers indicating activation of TGR5. It has been reported in our previous research paper that TGR5 activation could stimulate the secretion of GLP-2, which has been proven to be pivotal in improving intestinal barrier function and inflammation. It is therefore inferred that PAC probably could mediate gut health of piglets through TGR5/GLP-2 signaling pathway. In this project, vein catheterization will be manipulated and immunological stress model will be established to reveal that the modulatory effects of PAC on intestinal inflammation and barrier function of weaned piglets are dependent on TGR5/GLP-2. Enteroendocrine cell will be further used to demonstrate the mechanism through which PAC activates TGR5 and stimulates GLP-2 secretion. This project is aimed at elucidating the molecular mechanisms through which PAC modulates intestinal inflammation and barrier function, exploring novel target towards gut health regulation of piglets, and providing new insights into the nutritional modulation of gut health in weaned piglets.