AMPK-PINK1/Parkin介导的线粒体自噬在氧化应激诱导的仔猪肠屏障损伤修复中的作用及其营养调控

Oxidative stress is an important cause of impaired barrier of weaned piglets. Our previous experiments showed that weaning stress or oxidative stress disrupted intestinal antioxidant status, impaired intestinal barrier and mitochondrial function, and triggered mitophagy in piglets. However, the mechanisms have not yet been elucidated. In this project, the dynamic changes of intestinal barrier, mitochondrial function, mitophagy and AMPK-PINK1/Parkin pathway are studied in vivo and in vitro oxidative stress models. The restoration of intestinal barrier induced by oxidative stress will be evaluated after inhibiting or promoting mitophagy, or inhibiting AMPK in vivo and in vitro. The crosstalk of AMPK and PINK1/Parkin will be investigated in vitro. Finally, the effects of sodium butyrate on intestinal barrier, mitochondrial function and mitophagy will be studied in weaned piglets. The project was the first to explore AMPK-PINK1/parkin mediated mitophagy on restoration of intestinal barrier induced by oxidative stress in piglets and its nutrition regulation. The research will not only put forward some innovative concepts, but also provide a new target to the nutrition regulation of intestinal barrier function.

氧化应激是导致断奶仔猪肠屏障受损的重要原因。线粒体作为细胞的“动力工厂”，不仅是ROS产生的主要场所，也是ROS攻击的重要靶点。申请者前期研究表明，断奶和氧化应激均损伤线粒体，引发线粒体自噬；但线粒体自噬的作用及其调控机制均不清楚。本项目采用体内外氧化应激模型，研究氧化应激对线粒体自噬、AMPK-PINK1/Parkin信号通路的动态影响；抑制和促进线粒体自噬以及抑制AMPK信号通路对氧化应激诱导的肠屏障损伤修复的影响；深入探讨AMPK与PINK1/Parkin在肠屏障损伤修复中的对话机制；研究丁酸钠对仔猪肠道线粒体功能和自噬的影响。本项目首次探索线粒体自噬在氧化应激诱导的仔猪肠屏障损伤修复中的作用和调控机制，解析关键调节靶点，可望获得原创性学术观点，而且可为仔猪肠道健康的营养调控研究提供崭新的思路和方向，具有重要的理论意义和应用价值。

氧化应激是导致断奶仔猪肠屏障受损的重要原因。线粒体作为细胞的“动力工厂”，不仅是ROS产生的主要场所，也是ROS攻击的重要靶点。本项目采用体内外氧化应激模型，研究了氧化应激对仔猪肠屏障、线粒体功能、线粒体自噬、AMPK-PINK1/Parkin信号通路的影响；抑制线粒体自噬或抑制AMPK信号通路对氧化应激肠上皮细胞损伤修复的影响；阐明了AMPK-PINK1/Parkin介导的线粒体自噬对氧化应激仔猪肠屏障损伤修复的调控作用；明确了AMPK介导的线粒体自噬途径参与了丁酸盐的肠屏障保护作用。本项目探索了线粒体自噬在氧化应激诱导的仔猪肠屏障损伤修复中的作用和调控机制，解析了关键调节靶点，为仔猪肠道健康的营养调控研究提供了新的思路和方向，具有重要的理论意义和应用价值。