中文摘要
近年植物活性成分干预缺血性脑中风的研究备受关注。油莎草具有抗旱、耐盐碱等地域特色,前期大鼠脑缺血再灌注(MCAO)损伤的预试验结果表明油莎草醇提物显著干预缺血性脑中风,并且我们已经采用现代色谱分离和NMR波谱分析技术筛选出了以荭草苷(化合物4)为主的4种单体化合物。但油莎草对缺血性中风神经元的保护作用机制是否与抗氧化应激、炎症反应相关,目前仍不清楚。本课题拟采用生物化学、分子生物学、组织学等方法,在分子、细胞、整体水平揭示:(1)油莎草目标组分和单体化合物具有抗氧化活性;(2)油莎草目标组分和单体化合物具有抗炎症反应能力;(3)油莎草目标组分和单体化合物通过抑制JNK/c-Jun与Nrf2/ARE信号转导通路发挥其抗氧化及抗炎作用;(4)结合基因芯片高通量技术研究单体化合物干预缺血脑组织损伤的基因表达差异及作用靶点,揭示活性物质基础。最终阐明油莎草干预缺血性脑中风多靶点保护作用及分子机制。
英文摘要
There has been an increasing attention to the intervention of active ingredient from plant on ischemic stroke in recent years. Cyperus esculentus L.var.sativus Boeck. has many regional features,including drought resistance and alkali resistance. Our preliminary test results show that its alcohol extracts has significant intervention effect on ischemic/reperfusion injury of the middle cerebral artery occlusion (MCAO) model of rats. Furthermore, we have confirmed the structure identification of active monomer compounds by means of morden chromatographic separation techniques and NMR spectrum analysis technology and selected out of four kind of monomer compounds from target components with orientin as the main composition. However, it remains unclear that whether the protective effect of C. esculentus L. on neurons in ischemic stroke is associated with resistance to oxidative stress and inflammatory reaction, therefore, in our study, we plan to make use of the methods of biochemistry, molecular biology and histology and reveal at molecular, cellular and integral level (i) target component and monomer compounds of C. esculentus L. possess antioxidant activity; (ii) target component and monomer compounds of C. esculentus L. have the ability of resist inflammation; (iii) target component and monomer compounds of C. esculentus L. play the role of antioxidant and anti-inflammatory effects through the inhibition of JNK/c-Jun and Nrf2/ARE signal transduction pathways; (ⅴ) to reveal the active portion of C. esculentus L. through high-throughput microarray to investigate the differences in gene expression and its effect target of active monomer compounds on focal cerebral ischemia-reperfusion injury. The multiple targets for protection and the molecular mechanism of functional constituent from C. esculentus L. intervened ischemic stroke was finally demonstrated.
