仔猪小肠上皮隐窝绒毛轴更新与蛋白质代谢的分子机制

The small intestine is the major site for digestion and absorption of nutrients. Stem cell self-renewal in intestinal crypt is the basis of the digestion and absorption of nutrients and maintain intestinal barrier, protein metabolism is very important for proliferation, migration and differentiation of stem cells. However, little is known about the renewal along crypt-villus axes and protein metabolism. In order to solve the two scientific issues raised by the project, that processes about proliferation and differentiation of intestinal epithelial cells, protein metabolism and amino acid as regulators of proliferation and differentiation of intestinal stem cells. Cell biology, molecular biology, and omics-based approaches are employed as research tools, and the key genes and proteins involved in proliferation and differentiation of intestinal epithelial cells, the identification of intestinal stem cells markers in small intestinal crypts and amino acids as regulators of proliferation and differentiation of intestinal epithelial cell will be studied in sucking piglets, weaned piglets and intestine epithelial cell . The study could provide a theoretical basis for improving intestines health, nutrient use efficiency and reducing emissions through the dung burial, and the theory of amino acid nutrition of piglets.

动物小肠是营养物质消化吸收的主要部位。小肠上皮隐窝干细胞的不断增殖和分化是营养物质消化吸收和肠道屏障维持的基础，蛋白质代谢是小肠上皮细胞增殖、迁移和分化的前提，但目前对小肠上皮隐窝-绒毛轴更新与蛋白质代谢之间的内在联系还知之甚少。为了解决本项目提出的两个科学问题，即小肠隐窝-绒毛轴上皮细胞更新及蛋白质代谢机制和氨基酸/小肽对小肠发育的调控机制，本项目综合采用细胞生物学、分子生物学和现代组学等技术，以新生仔猪、哺乳仔猪和断奶仔猪为动物模型，以肠上皮细胞为研究对象，系统研究了隐窝-绒毛轴上皮细胞更新过程基因、蛋白质和代谢物质的变化规律、肠道干细胞的分离和鉴定、氨基酸转运载体的时空表达以及氨基酸/小肽对小肠上皮细胞分化过程的调控，为改善仔猪肠道及机体健康水平、提高营养物质利用效率、减少粪污排放对环境造成的污染提供理论依据和技术支撑，同时可完善猪的氨基酸营养理论。

动物肠道隐窝内干细胞沿隐窝-绒毛轴的增殖、分化和迁移是肠道结构维持和功能行使的基础，但该过程在猪上的研究还有待深入。本项目揭示了仔猪哺乳和断奶期小肠隐窝-绒毛轴发育及更新过程基因、蛋白质和代谢物的变化规律；成功完成了肠道干细胞的分离鉴定并建立了肠道隐窝三维培养模型；阐明了EAAT3、CDX2、乙醇胺和腐胺等对肠道更新的影响及机制。已有数据发表SCI论文32篇，申请专利5项。该项目结果为提高仔猪营养物质利用效率，减少粪污排放对环境造成的污染提供了理论基础。