Sulfiredoxin-1对脑缺血再灌注损伤的神经保护作用及机制研究

Sulfiredoxin-1（Srxn1）maight be one of the important endogeous antioxidant proteins ,but the main founctions and mechanisms underlying are poorly understood.In the presnt study,we will verify the hypothesis that Srxn1 inhibits oxidative stress after cerebral ischemia reperfusion injury, and this neuroprotective effect is likely regulated by activation of Nrf2/ARE signaliong pathway and the Peroxiredoxins(Prdxs) .We will further study the protective effects of Srxn1 against ishcheia reperfusion injury in vitro,following oxygen-glucose deprivation (OGD), and in vivo, after middle cerebral artery occlusion (MCAO) in rats.By using lentivirus miRNA and recombination techniques. real-time PCR.westen immnoblot analysis.immunofluorescende staining. and dual-luciferase reporter gene assay,the effects of Srxn1 on Prdxs.mitochondrion apoptotic pathway and the regulated Nrf2/ARE Signalling pathway will be measured.Then, we will establish a model in combination with in vitro assays can be used for the identification of selective and potent drugs. The aim of this study is to dicuss the mechanisms of the protective effect of Srxn1 on cerebral ischemia reperfusion, which will provide a academic basis for a more complete understanding of the Srxn1 in the brain,and which may also provide a promising drug target and opportunities to prevent stoke.

Sulfiredoxin-1（Srxn1）是中枢神经系统重要的内源性抗氧化小分子蛋白之一，但其具体神经保护功能及相关调控机制不清楚。基于前期NSFC研究结果，我们提出："在Nrf2/ARE信号通路的调控下，Srxn1可能作为关键蛋白，调控内源性蛋白Prdxs家族，阻断缺血级联反应，发挥神经保护功能，Srxn1将有可能成为药物干预研究的新靶点"。本课题拟在离体和在体脑缺血再灌注模型上，采用慢病毒RNA干扰和过表达技术、定量PCR、蛋白印迹、双荧光素酶报告基因检测等方法观察Srxn1对Prdxs家族、Nrf2/ARE通路、凋亡及炎症反应的作用及调控，并验证其相关机制。本课题实施将有助于充分阐明Srxn1的内源性神经保护机制，为高效筛选、设计及合成更有效的神经保护药物提供新靶点，为缺血性脑损伤的防治提供新策略。

Sulfiredoxin-1（Srxn1）是中枢神经系统重要的内源性抗氧化小分子蛋白之一，但其具体神经保护功能及相关调控机制不清楚。本课题在离体和在体脑缺血再灌注模型上，采用慢病毒RNA干扰和过表达技术、定量PCR、蛋白印迹、等方法观察Srxn1对Prdxs家族、Nrf2/ARE通路、凋亡及炎症反应的作用及调控，并验证其相关机制。我们发现：在Nrf2/ARE信号通路的调控下，Srxn1可能作为关键蛋白，调控内源性蛋白Prdxs家族，阻断缺血级联反应，发挥神经保护功能，Srxn1将有可能成为药物干预研究的新靶点。本课题实施将有助于充分阐明Srxn1的内源性神经保护机制，为高效筛选、设计及合成更有效的神经保护药物提供新靶点，为缺血性脑损伤的防治提供新策略。