SNAT2介导的猪小肠氨基酸感应机制研究

氨基酸是小肠优先利用的重要营养物质，对肠道黏膜更新和屏障功能起着重要作用。小肠如何感应氨基酸营养信息已成为营养研究领域的热点问题。某些氨基酸转运载体能通过转运过程调节细胞内氨基酸浓度，调控细胞内氨基酸受体下游信号，发挥着转运载体和受体的双重功能。我们前期的研究发现，很多氨基酸能调控SNAT2和细胞内氨基酸感应相关基因表达。因此，本项目拟采用Ussing Chamber技术和同位素示踪法，研究猪肠上皮细胞SNAT2介导的氨基酸转运机制；采用PCR Array等技术解析小肠SNAT2介导的氨基酸化学感应途径，研究SNAT2介导的GCN2和mTORC1信号通路；研究体内抑制仔猪SNAT2对肠道氨基酸营养感应信号的影响，验证SNAT2介导的氨基酸营养感应途径。项目旨在阐明SNAT2介导的小肠氨基酸营养感应机制，为仔猪肠道氨基酸营养调控提供理论依据，对提高氨基酸利用率、控制相关疾病具有重要意义。

Amino acids are preferential nutrients for the small intestine and play important roles in intestinal mucosal renewal and barrier function. How to sense the nutritional information of amino acids by small intestine has become a hot topic studied in the field of nutrition. Some amino acid transporters may act as receptors and regulate cellular amino acids contents and therefore modulate cellular downstream signaling of amino acid receptor. We previously showed that some amino acids can regulate the expression levels of SNAT2 and other genes related to amino acids sensing. Therefore, the project is conduct to reveal the mechanisms of amino acids transport mediated by SNAT2 in intestinal mucosa and epithelial cells by Ussing chamber and radioisotopiac trace and analysis the pathway of amino acids chemosensing and study cellular GCN2 and mTOR signaling pathway mediated by SNAT2 in small intestine using PCR Array; and then validate the pathway of amino acids sensing mediated by SNAT2 by study the effects of inhibiting SNAT2 on amino acids nutrient sensing signaling in vivo of pigs. The aim is to elucidate the chemosensory mechanism of amino acids mediated by SNAT2, providing the theory basis for nutritional regulation of intestinal amino acid in pigs, which is significant for improving amino acids utilization and controlling intestinal diseases.