抗性淀粉通过GLP-1途径保护肉鸭肠粘膜损伤的分子机制

研究发现，GLP-1具有保护肠道粘膜损伤的功能；抗性淀粉（RS）不但能促进肠道合成和分泌GLP-1,而且RS对肠道炎症也具有抑制作用。但RS能否通过GLP-1途径来保护肠道粘膜受损及其分子机制目前并不清楚。因此，本项目以肉鸭为研究对象，先确定适宜饲粮RS水平能够提高肉鸭肠道GLP-1合成与分泌及肠道粘膜屏障功能；再利用Ex(3-39)确定RS能够通过GLP-1途径保护肉鸭在LPS急慢性应激条件下的肠道粘膜损伤，并证实该保护作用与回肠TγδIELs数量增加有关；然后进一步通过体外试验，利用Ex(3-39)、利拉鲁肽、RS2体外发酵后SCFA来揭示RS保护机制在于GLP-1通过GLP-1R信号途径促进了TγδIELs增殖及免疫功能。本课题研究对于深入认识肉鸭营养调控原理及碳水化合物营养免疫功能具有重要理论和实践意义。

A number of studies showed that intestinal mucositis and other acute intestinal disorders might benefit from treatment with GLP-1 analogues. Resistant starch(RS) does not only involve the increased secretion of GLP-1 caused by RS fermented in the lower gut, but also RS can suppress gut inflammation. However, there are obscure whether RS protects intestinal mucosal damage via GLP-1 Pathway, and the mechanism underlying this protection remains unknown. Therefore, we hypothesised that RS can protect intestinal mucosal damage through the increased secretion of GLP-1, and this protective mechanism lies on modulating immune responses of the intestinal intraepithelial Tγδ lymphocyte (TγδIELs) through GLP-1R pathway. According to the scientific hypothesis, we firstly establish that dietary RS can increase the secretion of GLP-1 and improve the intestinal barrier function. Then we test RS can protect intestinal mucosal damage via GLP-1 pathway based on the acute intraperitoneal injection of LPS or the continuous intraperitoneal injection of LPS with GLP-1R antagonist. Finally, we revealed GLP-1 can promote the cell proliferation and immune responses of TγδIELs involved GLP-1R signaling based on GLP-1 analogue, GLP-1R antagonist and the mix SCFAs of fermented RS2 in vitro. The results of the project can provide theoretical and practical basis for nutritional regulation of meat duck and the nutritional immune function of carbohydrate.