miR-146a靶向ALDH2调控氧化应激的机制及其在肾脏缺血再灌注损伤中的作用

项目名称： miR-146a靶向ALDH2调控氧化应激的机制及其在肾脏缺血再灌注损伤中的作用

项目编号： No.81200547

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 袁清

作者单位： 中国人民解放军第三〇九医院

项目金额： 23万元

中文摘要： 氧化应激在肾脏缺血再灌注(IR)损伤中发挥关键作用，近期研究发现miRNA可能参与调控氧化应激，但机制仍不明确。我们采用miRNA芯片发现肾小管上皮细胞在H2O2刺激后miR-146a等表达上调，并经qRT-PCR法证实。结合我们所发现的乙醛脱氢酶2（ALDH2）在调控肾脏IR后氧化应激中的关键作用，经信息学预测和双荧光报告基因系统筛选发现miR-146a可能靶向ALDH2，并经预实验证实。由此提出假说：miR-146a可能靶向ALDH2参与调控肾脏IR后氧化应激。本项目拟研究IR对肾脏miR-146a表达的调控及其机制；联用小鼠同系肾移植冷/热缺血损伤模型，结合miR-sponge技术，探讨miR-146a靶向ALDH2的机制及在肾脏IR损伤中的作用，采用TLR通路相关缺陷小鼠，分析miR-146a调控ALDH2与其调控TLR通路的相互作用。本研究可为肾脏IR的临床治疗提供新的理论依据。

中文关键词： 肾脏；缺血再灌注损伤；氧化应激；乙醛脱氢酶2；miR-146a

英文摘要： Renal ischemia-reperfusion (IR) injury significantly increased mortality in renal transplant recipients. To date, no effective clinical treatment is available. Oxidative stress due to excessive production of reactive oxygen species (ROS) and subsequent lipid peroxidation plays a critical role in renal IR injury. Recent study found that miRNA may be involved in the regulation of oxidative stress, but the mechanism remains unclear. We found that several miRNA, including miR-146a, significantly upregulated within 24h after H2O2 treatment in mouse tubular epithelial cell by high throughput miRNA array, and further validated the expression by qRT-PCR. As our previous studies showed that the aldehyde dehydrogenase 2 (ALDH2) is a key molecule involved in the regulation of oxidative stress after kidney IR, we focused on miRNAs that have potential in targeting ALDH2. We found that miR-146a might target ALDH2 via computational miRNA target-gene prediction and Firefly Luciferase Reporter Gene Assay, and verified by cell transfection test. On this basis, this project intends to study the mechanism of miR-146a targeting ALDH2 in the modulation of oxidative stress during kidney IR. Syngeneic kidney transplantation cold ischemia model and bilateral kidney warm ischemia model will be used to better mimic the clinical condition

英文关键词： kidney；ischemia reperfusion injury；oxidative stress；ALDH2；miR-146a