通过COX-2/PGE2途径解析槲皮素缓解肉鸡肠道氧化应激导致黏膜屏障损伤的分子机制

家禽肠道问题是导致生长性能下降甚至死亡的重要原因。健全良好的肠道屏障功能是预防细菌、病毒、潜在性的有害物质等入侵机体的重要保证，决定养殖经济效益及畜禽产品质量。槲皮素是一种含量丰富的天然活性物质，具有抗氧化、调控肠炎等重要作用。预实验发现槲皮素能降低氧化应激、改善肉鸡肠道黏膜屏障功能。本项目拟采用动物试验和organoid细胞模型，研究槲皮素对肉鸡肠道氧化应激和黏膜屏障功能、COX-2和mPGEs-1的表达以及PGE2分泌的影响机制；运用微生物16s测序和二代测序等技术，结合肠道屏障功能指标，揭示槲皮素对肉鸡肠道黏膜屏障的调控机制。然后，过表达或干扰/敲除COX-2和mPGEs-1等关键基因以及抑制剂阻断相关调控通路，研究槲皮素如何通过COX-2/mPGEs-1/PGE2途径降低氧化应激、调控肠黏膜屏障功能的分子机制。该研究对于调控肉鸡肠道黏膜屏障功能具有重要理论和实践指导意义。

Intestinal problems in poultry are the main causes of decline in growth performance and death. Intestinal barrier function is important in preventing bacteria, viruses and potential harmful substances from invading the body. It guarantees the economic benefit of farming and the products quality of poultry. Quercetin is a natural flavonoid found abundantly in edible vegetables and fruits, exerting both antioxidative and anti-inflammatory functions in intestine. Our preliminary experiments showed that quercetin could reduce oxidative stress and improve intestinal mucosal barrier function in broiler chickens. In this project, animal experiments and organoid culture will be used to study the effects of quercetin on intestinal oxidative stress and intestinal mucosal barrier function. The expression of COX-2 and mPGEs-1, and the secretion of PGE2 in intestine of broiler chickens will be analyzed. To understand the mechanism of quercetin on intestinal mucosal barrier, 16S sequencing and Next-generation sequencing will be performed. Lastly, we will study the molecular mechanism of quercetin in alleviating intestinal mucosal barrier dysfunction under oxidative stress in broiler chickens whether through some key genes such as COX-2 and mPGEs-1 by gene overexpression or interference/knockout. Specific inhibitors targeting signaling pathways of interested will also be used. This study will provide important theoretical and practical guidance for modulating intestinal mucosal barrier function in broiler chickens.