转录因子ZNF580 在缺血-再灌注脑损伤中的作用及分子机制

项目名称： 转录因子ZNF580 在缺血-再灌注脑损伤中的作用及分子机制

项目编号： No.81200223

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 罗玉玉

作者单位： 中国人民武装警察部队后勤学院

项目金额： 23万元

中文摘要： 人ZNF580基因由本课题组首先克隆，其编码的蛋白为锌指核转录因子家族的新成员。研究证实：ZNF580可能参与TGF-β1信号转导通路，并与活性依赖的神经保护蛋白（ADNP）间可能存在相互作用。文献显示：TGF-β1和ADNP对缺血-再灌注脑损伤都具有重要的保护作用，且作用机制相似。重要的是二者都与ZNF580之间存在密切联系。本课题拟应用免疫共沉淀、免疫荧光标记、荧光素酶报告载体实验、RNA干扰技术、基因芯片筛选等方法初步阐明ZNF580在神经胶质细胞中发挥的作用及其参与的信号转导通路。并在脑缺血-再灌注大鼠模型中应用Real-time PCR、Western blot、免疫组化等实验方法进一步研究ZNF580可能的神经保护作用及其分子机制，为临床寻找治疗脑缺血-再灌注损伤的新靶点提供理论和实验依据。

中文关键词： ZNF580；ADNP；缺血-再灌注；脑损伤；转录因子

英文摘要： Human ZNF580 gene was cloned by our research group. It encodes a novel C2H2 zinc finger transcriptional factor. Our previous studies showed that ZNF580 might be involved in the TGF-β1 signal transduction pathway, by which it played the role of regulating the vascular endothelium homeostasis. ZNF580 might be interacted with activity-dependent neuroprotective protein (ADNP). Many studies confirm that both of ADNP and TGF-β1 have important protective effects on ischemia-reperfusion cerebral injury. Furthermore, both of them play their protective roles on the same mechanisms. But more importantly, both of them have close correlation with zinc finger transcriptional factor ZNF580. We propose that the activation of TGF-β1 signaling pathway might up-regulate the transcription of ZNF580 and further activate the transcription of ADNP in ischemia-reperfusion cerebral injury, which promotes ADNP secretion from neurogliocytes and protects the microvascular endothelium and neurocytes. In this study,we will try to reveal the role and the signal transduction pathway of ZNF580 involved in neurogliocytes by some of experiments, such as co-immunoprecipitation, immunofluorescence labeling, luciferase report essay, siRNA essay, microarray-based gene expression profiles. We will further investigate the possible neuroprotective role

英文关键词： ZNF580；ADNP；ischemia-reperfusion；cerebral injury；transcriptional factor