急性肾损伤（AKI）是临床常见危重症，缺血/缺氧是AKI的主要致病因素，免疫炎症反应失控则是推动缺血性AKI发生发展的重要机制。低氧反应调节的核心低氧诱导因子（HIF）及其可能调控的重要低氧相关miRNA miR-21均被证实参与免疫炎症反应过程。我们前期工作发现短时间缺血预处理可以减轻长时间肾脏缺血所致的肾损伤与免疫炎症反应，并活化HIF-miR21信号系统，推测该信号系统可能参与调控缺血性肾损伤的免疫炎症反应。本项目拟在阐明肾脏缺血/缺氧时HIF与miR-21相互调控机制的基础上，分别从分子、细胞、动物模型三个层面，采用基因修饰等方法，以HIF-miR21-靶基因为主线，研究缺血性AKI过程中免疫炎症的信号机制及肾小管上皮细胞与树突状细胞的交互作用，并进一步以miR-21为靶点寻找干预AKI的新技术，从而为AKI临床早期诊断和防治提供新思路和新策略。

Acute kidney injury (AKI) is a common clinical critical disease, the main cause of which is renal ischemia/hypoxia. Uncontrolled immune-inflammatory response is an important mechanism in the progression of ischemic AKI. The core regulatory factor of hypoxic response is hypoxia inducible factor (HIF) and important hypoxia-related miRNA miR-21 is possibly regulated by HIF. Both of them were confirmed to participate in immune-inflammatory response. On the basis of our previous studies of the mechanism of ischemic kidney injury, we found that short period of ischemic preconditioning ameliorated kidney injury and immune-inflammatory responses after the subsequent prolonged renal ishcemia, which accompanied with activation of HIF-miR21 system. Therefore, it is speculated that this signaling system may be involved in the regulation of immune-inflammatory response during ischemic AKI. Building upon the mutual regulatory mechanism between HIF and miR-21, we want to further clear the role of HIF-miR21-target gene signaling pathway in the modulation of the immune-inflammatory responses and the interaction between tubular epithelial cells and dendritic cells in the process of ischemic AKI through gene modification methods, as well as the estiblishment of molecular, cellular and animal models. Finally, we try to search new technologies to intervene AKI targeted as miR-21 in order to provide new ideas and new strategies for the early diagnosis and prevention of AKI clinically.