糖尿病肾脏缺血再灌注损伤中氧化应激起着至关重要的作用。Nrf2是迄今阐明的调控细胞对抗氧化应激损伤最重要的转录因子。我们的前期研究发现促进Nrf2表达能有效减轻肾脏氧化应激损伤。新近研究显示DJ-1作为新的抗氧化应激基因，能结合抑制蛋白keap1以稳定Nrf2的表达。本研究组预实验显示，高糖条件下缺氧复氧期间肾小管上皮细胞DJ-1表达显著减少，且与其损伤高度相关。但在糖尿病肾脏缺血再灌注损伤病理机制中，DJ-1调控keap1/Nrf2信号通路的分子机制及作用亟待阐明。本研究拟通过在体动物和离体细胞实验，应用Nrf2激动/拮抗剂、DJ-1基因剔除以及DJ-1基因过表达和沉默等技术，探讨在糖尿病肾脏缺血再灌注损伤病理过程中DJ-1的改变以及对keap1/Nrf2信号通路的调控作用及分子机制，以期为有效防治糖尿病肾脏缺血再灌注损伤提供实验依据和新的思路。

Oxidative stress plays an important role on diabetic renal ischemia reperfusion injury (IRI). Nrf2 is the most significant transcription factor against oxidative stress injury. Our study found that the activation of Nrf2 could attenuate renal oxidative stress injury effectively. And DJ-1, that is the new anti-oxidative gene, can inhibit keap1 to stabilize the expression of Nrf2. Our preliminary experiments showed that the expression of DJ-1 in renal tubular epithelial cells induced by high glucose was decreased significantly during hypoxia/reoxygenation treatment, which was highly correlated with renal injury. Therefore, how DJ-1 regulated keap1/Nrf2 signal pathway in diabetic renal IRI is needed to be elucidated. This research investigate the mechanism of keap1/Nrf2 signal pathway regulated by DJ-1 on diabetic renal IRI using Nrf2 activator/antagonist, DJ-1-knockout in vivo and siRNA-mediated DJ-1 knockdown ex vivo. The aim is to provide experiment basis and new thought for prevention and treatment of diabetic renal IRI.