碘造影剂急性肾损伤（CIAKI）主要发病机制与氧化应激、肾缺血及直接肾毒性有关。前期研究发现过度的活性氧簇（ROS）的产生在碘造影剂致肾小管上皮细胞凋亡中起重要作用。预实验初步表明碘造影剂碘海醇诱导肾小管上皮细胞线粒体ROS生成增多、线粒体损伤及线粒体自噬，但线粒体自噬在急性肾损伤中的作用机制尚不清楚。本课题拟采用既往建立的碘造影剂急性肾损伤动物模型和细胞模型，验证不同渗透压碘造影剂致肾小管上皮细胞线粒体损伤和自噬的程度，以明确不同渗透压的碘造影剂与线粒体自噬程度关系；然后探讨碘造影剂造成的线粒体损伤是否是线粒体自噬激活的诱因；采用基因过表达或抑制方法, 探讨PINK1-Parkin，BNIP3和Nix是否参与了对CIAKI肾小管上皮细胞中的线粒体自噬的调控；线粒体自噬是否对CIAKI具有保护作用。该项目旨在阐明线粒体自噬在CIAKI发生中的分子机制，为CIAKI防治提供新的靶点。

The pathogenic mechanism of iodinated contrast-induced acute kidney injury (CIAKI) is mainly associated with oxidative stress, renal ischemia and direct nephrotoxicity. Previous studies found that excessive ROS generation play a pathogenic role in apoptosis induced by contrast media. We also found that iodine contrast media iohexol induce mitochodrial ROS generation, mitochodrial damages, and mitophagy in proximal tubule epithelial cell HK-2 cell, but the role and mechasnism of mitophagy in CIAKI remain unknow. In the project, we use the previously-established CIAKI animal model and cell model and focus on determining 1) whether different osmolar iodine contrast media induce mitochondria damages and mitophagy, confirm the relationship between different osmolar iodine contrast media and the degree of mitophagy; whether iodine contrast media active mitophagy through inducing mitochondria damages; 2) whether mitophagy in CIAKI is mediated by PINK1-Parkin or by receptor proteins BNIP3 and Nix, as detection methods by over-expression or suppression a gene; 3) whether mitophgy palys a cytoprotective role in CIAKI. The overall goal of this study is to delineate the molecular mechanisms of mitophagy in CIAKI and explore therapeutic strategy for CIAKI.