色氨酸分解代谢对断奶仔猪肠细胞损伤的保护作用和分子机制

Intestinal mucosal injury is one of the main causes of growth retardation and high incidence in weaned piglets. Animo acids can protect the intestinal mucosa injury by reducing intestinal oxidative stress and inflammatory response, which has caused more and more attention of researchers in the fields of animal nutrition and clinical nutrition in recent years. Tryptophan is a kind of the essential amino acids to promote cell proliferation for animals. Tryptophan is known to influence protein synthesis in liver, gene regulation, growth-promoting and nerval function as a precursor of serotonin. However, the mechanism of tryptophan and its metabolites via kynurenine pathway on intestinal epithelium oxidative damage and mucosal immunity remains unclear. We investigate the catabolism of tryptophan via kynurenine pathway and the protective effect of tryptophan and its metabolites on intestinal oxidation with morphological techniques, flow cytometry, western blot, molecular biology and metabolomics technology in weaned piglets and IPEC-1 cells. It may expound the molecular mechanisms of tryptophan on intestinal epithelium oxidative damage. This study will provide new theoretical basis for tryptophan protecting intestinal oxidation and immune homeostasis in piglets, even intestinal injury in young animals.

肠道黏膜损伤是仔猪断奶后生长阻滞与高发病率的最主要原因之一。通过降低肠道黏膜氧化应激和伴随的免疫炎症来保护肠黏膜损伤，已经引起一些发达国家动物营养与临床营养等领域研究者的高度重视。色氨酸是哺乳动物体内细胞维持活化和增殖所必需的氨基酸。色氨酸在促进肝脏蛋白质合成、调节基因、代谢为血清素（神经递质）调节肠道生理与促生长，调节神经功能等方面作用规律较清楚。但是，色氨酸及犬尿氨酸分解途经代谢物（如犬尿氨酸和喹啉酸）调控肠上皮细胞氧化和黏膜免疫的机理仍然不清楚。本项目通过猪上皮细胞IPEC-1 氧化损伤模型和仔猪动物实验，采用形态学技术、流式细胞术、免疫印迹、分子生物学和代谢组学技术，系统研究色氨酸/犬尿氨酸途经代谢物在仔猪肠道中的代谢规律，探讨色氨酸及其代谢物对肠黏膜细胞线粒体氧化损伤的保护机制。为保护仔猪肠道代谢氧化与免疫稳态，以及氨基酸干预/保护幼年动物肠道损伤提供新的理论依据。

肠道黏膜损伤是仔猪断奶后生长阻滞与高发病率的最主要原因之一。 通过降低肠道黏膜氧化应激和伴随的免疫炎症来保护肠黏膜损伤已经引起一些发达国家动物营养与临床营养等领域研究者的高度重视。 色氨酸是哺乳动物体内细胞维持活化和增殖所必需的氨基酸。色氨酸在促进肝脏蛋白质合成、调节基因、代谢为血清素（神经递质）调节肠道生理与促生长，调节神经能等方面作用规律较清楚。但是，色氨酸及犬尿氨酸分解途经代谢物（如犬尿氨酸和喹啉酸） 调控肠上皮细胞氧化、肠道屏障和黏膜免疫的机理仍然不清楚。 本项目通过仔猪动物实验采用形态学技术、代谢组学、免疫印迹和分子生物学技术，发现色氨酸/犬尿氨酸途经代谢物（Kyn与3-HAA）在血清中含量增加，揭示了色氨酸降低猪肠道屏障（增加通透性），对线粒体氧化损伤的保护机制。 为保护仔猪肠道代谢氧化与免疫稳态，以及氨基酸干预/保护幼年动物肠道损伤提供新的理论依据。