LncRNA-snhg17通过与CYP2J2结合影响EETs生成调控线粒体自噬通路保护缺血性脑损伤的机制

缺血性脑损伤致残率及死亡率高，寻找有效治疗靶点是全球重大热点问题。细胞色素P450表氧化酶2J2(CYP2J2) 在脑组织高表达，可代谢生成环氧化二十碳三烯酸(EETs)，具扩血管等功能。前期已证实上调CYP2J2促EETs生成对急性脑梗死有保护作用，通过高通量测序发现对缺氧脑损伤有潜在保护作用的lncRNA-snhg17，预实验发现其可与CYP2J2结合，生物信息学预测转录因子FOXP1可上调lncRNA-snhg17，且下游可干预线粒体膜蛋白TSPO介导线粒体自噬通路。本项目采用分子生物学、临床数据收集等方法：①揭示转录因子FOXP1-lncRNA-snhg17-CYP2J2-EETs通过调控线粒体自噬通路，发挥对缺血缺氧脑损伤的保护作用的机制；②发现关键靶分子lncRNA-snhg17、CYP2J2，为脑缺血的药物研发提供理论支持，有助于预防脑梗死发生，建立脑梗死早期预警体系。

The disability rate and mortality of ischemic brain injury are high. Cytochrome P450 expression oxidase 2J2(CYP2J2) is highly expressed in brain tissue, which can metabolize to produce epoxide dicarboxylic acid (EETs), and has the function of expanding blood vessels。 We have preliminary confirmed that raised CYP2J2 promote EETs to generate a protective effect on acute cerebral infarction, through high-throughput sequencing we found lncRNA-snhg17, which may have a potential protective effect on hypoxic brain damage of, it was found that it can combine with CYP2J2. We also found bioinformatics prediction of transcription factor FOXP1 can raise lncRNA-snhg17, and downstream can intervene in the mitochondrial membrane protein TSPO mediated mitochondrial autophagy pathways. In this project, molecular biology and clinical data collection methods were used to reveal the following key points: (1) the mechanism by which the transcription factor FOXP1-lncRNA-snhg17-CYP2J2-EETs exerts its protective effect on ischemic hypoxic brain injury by regulating the mitochondrial autophagy pathway.(2) to find key target molecules lncRNA-snhg17 and CYP2J2, to provide theoretical support for the drug research and development of cerebral ischemia, to help prevent the occurrence of cerebral infarction, and to establish an early warning system of cerebral infarction.