七叶皂苷钠调控NOX家族蛋白介导的MAPK、PI3K/AKT信号通路保护神经细胞氧化应激损伤

项目名称： 七叶皂苷钠调控NOX家族蛋白介导的MAPK、PI3K/AKT信号通路保护神经细胞氧化应激损伤

项目编号： No.31301171

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 齐世美

作者单位： 皖南医学院

项目金额： 20万元

中文摘要： 七叶皂苷钠是娑罗子中提取的三萜皂苷钠盐，商品名Reparil，临床用于抗渗出、改善循环、促进脑功能恢复。研究证明其能提高SOD活性，但七叶皂苷钠能否改变神经细胞的氧化应激状态，治疗神经退行性疾病，其保护神经细胞的具体分子机制和生物标靶尚不清楚。申请者在PC12细胞H2O2损伤模型中发现，七叶皂苷钠能够降低H2O2引起的细胞凋亡，改善细胞核凋亡形态学变化，减少细胞内ROS的生成。本项目将深入分析七叶皂苷钠对PC12细胞和原代大脑皮层细胞的H2O2损伤保护及相关信号转导的影响，阐明具体的分子机制。主要包括：1)构建PC12和原代大脑皮层细胞氧化应激模型；2）降低H2O2引起的细胞损伤和细胞内ROS水平；3) 对MAPK和PI3K/AKT信号通路和转录因子AP-1转录活性的影响；4）细胞内ROS生成的亚细胞定位及生成酶；5）NOX家族蛋白是细胞保护作用的关键因子；6）对NOX家族蛋白的调控机制。

中文关键词： 活性氧簇；天然提取物；细胞信号转导；细胞凋亡；炎症

英文摘要： Sodium aescinate is the triterpenoid saponins sodium salt extracted from Aesculus Chinese Buckeye Seed, trade name Reparil. Clinically it can reduce exudative, improve circulation, and promote the recovery of brain function. Experiments prove that it can improve the activity of SOD. But whether sodium aescinate can change the oxidative stress status of the nerve cells, treat neurodegenerative diseases as well as the specific molecular mechanisms and biological targets is unclear. The applicant recently found that sodium aescinate can decrease the PC12 cells growth inhibition rate and apoptosis rate in H2O2 injury model. Furthermore, sodium aescinate can improve the apoptotic morphological changes of the nucleus and reduce the intracellular ROS level. In the present program, we will investigate the impact of sodium aescinate in H2O2-induced PC12 cell and primary cortical cells injury as well as the signal transduction and clarify the specific molecular mechanism. The project includes building PC12 cells and primary cortical cells oxidative stress models, the regulatory effect of sodium aescinate on H2O2-induced apoptosis and ROS level in nerve cells, the MAPK and PI3K/AKT cell survival pathway and AP-1 transcriptional activity. In addition, we probe ROS generation subcellular localization and interrelated enzyme，

英文关键词： ROS；natural extracts；cell signal transduction；cell apoptosis；inflammation