缺血预处理（IPC）可明显减轻随后发生的急性肾损伤，其分子机制并未完全明了。Renalase是新近发现的肾脏来源的一种黄素蛋白，可分解循环儿茶酚胺并具有细胞因子样功能。申请人首次报道了NFκB可介导renalase表达；renalase可以保护造影剂肾损伤；首次发现IPC上调renalase表达并参与了IPC的肾脏保护。申请人假设“缺氧通过激活HIF-1α与NFκB两条通路并存在crosstalk，上调renalase，参与了IPC的肾脏保护机制”。为验证该假设，申请人拟利用体外和体内实验分别或联合抑制NFκB与HIF-1α，研究IPC诱导的renalase表达变化；利用renalase敲除小鼠观察renalase缺失是否逆转了缺血预处理的肾脏保护效应。将为进一步阐明IPC的肾脏保护机制提供实验依据，为renalase的临床应用奠定基础。

It has been shown that ischemic preconditioning (IPC) can alleviate the subsequent acute kidney injury (AKI). However, its molecular mechanism is not well understood. Renalase is a novel flavin adenine dinucleotide-dependent oxidase that is secreted into circulation by the kidney to degrade catecholamines. We found that renalase expression was regulated by NFκB pathway and renalase could also protect against contrast-induced nephropathy. We first reported that IPC up-regulated renalase expression and renalase played a key role in renal protection of IPC. We hypothesize that hypoxia triggers the crosstalk between hypoxia-induced factor 1α (HIF-1α) and NFκB to up-regulate renalase following IPC. We aim to investigate the changes of renalase expression after blocking NFκB and HIF-1α pathways following IPC in vitro and in vivo. The aim of the project is to prove that hypoxia up-regulates renalase expression via NFκB/HIF-1α pathways, which participate in the renal protection mechanisms of IPC. The current project will elucidate a novel pathway in renal protection of IPC, and will provide important data for the clinical utilization of renalase as a new therapeutic target.