基于AMPK-ULK线粒体自噬途径探索猕猴桃多酚对肠黏膜上皮屏障功能的保护作用

肠黏膜上皮屏障在维持机体健康中起着关键性作用，其功能损伤与肥胖、糖尿病等多种疾病发生和发展密切相关。研究显示，膳食多酚类化合物能改善肠黏膜上皮屏障功能，但其作用机制不清楚。课题组前期研究显示猕猴桃多酚能缓解高脂膳食造成的肠道通透性增加，提高肠黏膜紧密连接蛋白mRNA的表达和线粒体呼吸链复合酶的活性，其对肠黏膜上皮屏障功能损伤是否与线粒体功能的恢复有关并不清楚。鉴于线粒体自噬在维持线粒体功能中的关键作用，本项目假设猕猴桃多酚能通过促进线粒体自噬改善肠黏膜屏障功能。项目拟通过动物实验结合细胞培养，运用形态学、免疫荧光组织化学、流式细胞术、蛋白质印记等技术，研究猕猴桃多酚对肠黏膜上皮紧密连接蛋白分布、线粒体功能的影响，并从AMPK-ULK自噬途径探索猕猴桃多酚对肠黏膜上皮屏障功能保护作用的机理。该项目的完成为膳食多酚预防与肠黏膜损伤有关疾病的发生，促进机体健康，提供理论支撑。

Intestinal epithelial barrier plays a key role in maintaining body health, and its impairment is related to the occurrence and development of many diseases, including obesity and diabetes. Recent studies have shown that dietary polyphenols may improve the function of intestinal barrier, but the mechanism is still unclear. The previous research results of the our group showed that kiwifruit polyphenols can alleviate the increase of intestinal permeability caused by high-fat diet, and improve the expression of mRNA in tight junction protein and the enzymatic activity of mitochondrial respiratory chain complex, but we don’t know whether the mitigative effect of kiwifruit polyphenols on intestinal barrier function is related to the recovery of mitochondrial function. Given the critical role of mitophagy in maintaining mitochondrial function, this project hypothesized that kiwifruit polyphenols could improve intestinal barrier function by promoting mitophagy. The project intends to study the effects of kiwifruit polyphenols on the distribution of tight junction proteins and mitochondrial function in intestinal epithelium cell, and explore the protective effect and mechanism of kiwifruit polyphenols on intestinal barrier function based on AMPK-ULK signal pathway of mitophagy，through animal experiments combined with cell culture, using morphology, immunofluorescence histochemistry, flow cytometry, protein imprinting and other techniques. So, the completion of this project can provide theoretical support for the prevention of diseases related to intestinal mucosal injury by dietary polyphenols and the promotion of health.