脓毒症患者急性肾损伤（AKI）的发生率高、预后差。炎症反应和细胞凋亡是脓毒症性AKI的重要病理生理机制。已证实miR-21参与细胞凋亡和免疫炎症的调控，在AKI的发生和修复中起重要作用。我们发现，肾脏缺血预处理可上调miR-21表达，抑制程序性细胞死亡因子4（PDCD4），抑制细胞凋亡，减轻肾脏缺血性损伤。预实验亦初步证实小鼠后肢缺血预处理可上调局部组织和肾脏miR-21的表达，且能减轻内毒素血症诱发的肾损伤，但具体机制尚不清楚。我们推测肢体缺血预适应上调局部组织miR-21表达，miR-21再通过内分泌机制，到达远隔器官，发挥抗凋亡和抗炎作用。本项目在前期研究基础上，拟通过miR-21基因敲除小鼠和野生型鼠的脓毒症AKI模型，深入探讨肢体缺血预适应对脓毒症性肾损伤的防治作用及其机制，阐明肢体缺血调控局部和远隔器官miR-21/PDCD4通路的分子机制，从而为AKI的防治提供新策略和靶点。

Acute kidney injury (AKI) is a common and life-threatening complication in patients with sepsis. Inflammation and cell apoptosis are important pathophysiological mechanisms of septic AKI. It has been demonstrated that miR-21 is an important gene in regulating apoptosis and inflammation, involving in the development and repair of AKI. Our previous studies showed that renal ischemic preconditioning upregulated miR-21 expression in kidneys in time-dependent manner, inhibited programmed cell death 4 (PDCD4) expression, and protected against renal ischemia-reperfusion injury via inhibiting apoptosis. Our preliminary experiment exhibited that limb ischemic preconditioning (LIPC) upregulated miR-21 in gastrocnemius muscle, as well as in kidneys, and reduced endotoximia-induced renal injury in mice, but its mechanisms are not clear. We hypothesize that limb ischemic preconditioning increased expression of miR-21 in local tissue, and the miR-21 is released into circulation, transferred to remote organs as a potent endocrine factor, exerts anti-apoptotic and anti-inflammatory effects. In this study, with the septic AKI model in miR-21 knock out mice and wild mice, we further explore the protective effects of LIPC on apoptosis and inflammation, and its underlying mechanisms, and elucidate the potential mechanisms that limb ischemia regulates miR-21/PDCD4 pathway in local tissue and remote organ (kidney). This study will provides a new strategy and target for the prevention of septic AKI.