AMPK和mTORC1介导氨基酸调控仔猪小肠黏膜能量利用与损伤修复

断奶应激常常会导致能量摄入量不能满足其需要量，改善黏膜细胞能量供应和利用，是缓解仔猪断奶应激、充分发挥生长潜力的有效手段。本项目拟采用细胞线粒体呼吸代谢检测技术，研究猪小肠上皮细胞对氨基酸作为能量底物的差异利用，筛选最佳氨基酸供应模式；通过分别激动或抑制AMPK和mTORC1，研究AMPK和mTORC1交互调控小肠上皮细胞线粒体呼吸代谢、线粒体功能、能量代谢及其相关信号通路的作用；利用LPS或H2O2诱导小肠上皮细胞损伤，研究氨基酸供应模式对应激损伤小肠上皮细胞线粒体功能以及能量感应通路的影响；利用断奶应激模型，研究不同能量底物供应模式对仔猪小肠黏膜形态结构、能量代谢及其感应信号通路的调控作用。以期阐明AMPK和mTORC1交互调控仔猪小肠黏膜能量利用机制，优化小肠黏膜能量底物供应模式，促进断奶仔猪肠道黏膜更新，为缓解能量供应不足、促进肠黏膜损伤修复、发挥生长潜力提供营养调控手段。

Weaning stress leads to the shortage of energy intake and improvement of mucosal energy supply and utilization is the effective method to alleviate weaning stress and fully develop the growth potential of the piglets. The project is conduct to study the differences in utilizations of amino acids as energy substrates in porcine small intestinal epithelial cells and obtain the optimal amino acids model for cell by detecting the mitochondrial respiratory metabolism; investigate the interactive regulation of AMPK and mTORC1 on mitochondrial respiratory and function, energy metabolism, as well as related signaling pathway via stimulating or inhibiting the AMPK or mTOR; study the effects of amino acids model as energy substrates on mitochondrial function, AMPK and mTORC1 signaling pathway using the damage enterocyte model induced by LPS or H2O2; investigate the effects of different energy substrates supply on intestinal morphology, energy metabolism and the signaling pathway of energy sensing in weaning piglets. The results is to clarify the mechanism of interactive effects of AMPK and mTORC1 on energy utilization, optimize the energy substrates supply model and improve the mucosal renewal in small intestine of piglets. The aim is to provide nutritional regulated manners of improving nutritional status, mucosal damage repair and growth potential in early weaned piglets.