尿毒症毒素硫酸吲哚酚(IS)是慢性肾病(CKD)的重要致伤因素，也是CKD肠道损伤的重要原因，但机制不清。近期研究表明IS能抑制线粒体功能，我们前期研究发现CKD小鼠肠黏膜受损；且IS能抑制肠上皮细胞的线粒体自噬及其调控基因DRP1表达。鉴于线粒体自噬对肠上皮细胞的重要作用，我们推测：IS可能通过DRP1抑制线粒体自噬，进而导致肠道功能紊乱。本项目拟在此基础上，首先在动物模型和临床样本中检测CKD导致的肠道损伤和线粒体自噬变化；然后在细胞实验中分析IS抑制线粒体自噬的效应与机制，阐明STAT3-DRP1信号通路在其中的作用；最后在体外和小鼠模型中解析肠道吸附剂AST-120对IS引起的肠道损伤和线粒体自噬效应的干预效果，并在临床样本中验证肠道损伤程度与IS、STAT3、DRP1的相关性。本项目对探索CKD并发肠功能紊乱的发病机制及其防治策略具有重要的临床指导意义。

Uremic toxin indoxyl sulfate (IS) is a significant injury factor of chronic kidney disease (CKD) and also an important cause of intestinal dysfunction of CKD patients, but the mechanism remains elusive. Recent research has shown IS could lead to mitochondrial dysfunction. Intestinal mucosal injury of CKD mice, inhibition of mitophagy and its regulatory gene DRP1 regulated by IS were observed in our preliminary work. Considering the important role of mitophagy in intestinal epithelial cells, we speculate that IS might inhibit DRP1-mediated mitophagy, which contributes to intestinal dysfunction. Therefore, based on these results, we would detect intestinal injury and mitophagy caused by CKD and analyze the effect of IS on mitophagy and STAT3-DRP1 signaling pathway to illuminate the mechanism. Finally, we elaborate the intervention effect of intestinal adsorbent AST-120 on IS-mediated intestinal dysfunction and mitophagy in intestinal cells and the mouse model, and validate the relevance among IS, STAT3 and DRP1 expression in clinical samples. This research explores the pathogenesis of CKD complicated with intestinal disorders and its prevention strategy, which has clinical significance.