腐胺调控仔猪肠粘膜上皮细胞增殖和损伤修复的分子机制

The intestine is an organ not only to digest and absorb nutrients but also to provide the first line barrier preventing bacterial invasion. The atrophy and dysfunction in the intestine induced by weaning usually causes piglet’s diarrhea and decreased growth performance. Understanding repairing mechanism of intestinal damage caused by weaning is the key scientific question to answer. Putrescine is one of polyamines which have functions to enhance enterocytes proliferation and intestinal epithelial restitution, however, the underling mechanism is not clear yet. Our scientific hypotheses are: (1) putrescine enhances the proliferation of enterocytes by regulating AMPK/ERK signaling pathway; (2) putrescine increases the migration of enterocytes by regulating Focal adhesion signaling pathway; (3) putrescine supports intestinal epithelial restitution through regulating the migration and proliferation of the enterocytes. We will explore the signaling pathways of putrescine regulating cell proliferation and epithelial restitution through both in vivo and in vitro studies. Using the advanced technologies such as Microarray, RT-PCR, Western blotting, as well as immunofluorescence, the key genes involved in AMPK/ERK and Focal adhesion signaling pathway regulated by putrescine will be studied to understand the mechanism of intestinal epithelial restitution promoted by putrescine supplementation in the diet of weaning piglets, which will provide the basis for developing new ways to enhance intestinal maturation and health in piglets.

肠道是猪营养物质消化吸收和抵御外界病菌侵害的重要器官。由于仔猪断奶等应激引起的肠粘膜损伤会造成仔猪腹泻和生长性能下降。探索肠粘膜损伤修复的生物学机制对提高养猪生产效益具有重大科学意义。腐胺作为一种多胺类小分子具有类生长因子功能，能促进肠细胞增殖分化和损伤修复，但其作用机制尚不清楚。本申请拟从以下三个方面开展研究：（1）腐胺通过调控AMPK/ERK信号通路促进仔猪肠粘膜上皮细胞增殖分化；（2）腐胺通过调控Focal adhesion信号通路促进仔猪肠粘膜上皮细胞迁移；（3）腐胺通过调控细胞增殖和细胞迁移修复由断奶应激引起的肠粘膜损伤。本研究拟采用日粮添加腐胺和猪肠粘膜细胞培养来研究腐胺对肠粘膜上皮细胞增殖和损伤修复的作用。通过筛选腐胺调控细胞增殖和细胞迁移信号通路中的节点基因及对其基因表达的分析，揭示腐胺调控仔猪肠粘膜损伤修复的机理。本研究为开发新型仔猪肠道健康促进剂提供新的理论基础。