中文摘要
中风也叫脑卒中,由于其高发病率、高死亡率、多并发症的特点,已经和冠心病、恶性肿瘤并列为威胁人类健康的三大疾病之一。近来的研究结果表明不仅兴奋毒、氧化应激参与了脑缺血性细胞损伤和功能障碍的过程,表观遗传调控也在其中发挥着重要作用,其中就包括微小RNA(miRNA)。我们前期芯片的实验结果表明:miR-137可能就是这样一个重要的miRNA。但miR-137通过哪个或哪些靶基因,如何调节缺血性细胞损伤,与后期的认知功能障碍有什么联系,将是我们拟申请项目所要解决的关键问题。我们希望通过本项目的实施,1)阐述miRNA-137在缺血复灌不同时期的表达模式,分析其被调控的机制;2)明了脑缺血过程中miRNA-137可能作用的靶基因;3)构建miRNA-137的靶向递药载体,观察其疗效。从而找到一条以miRNA-137为分子桥梁的参与调控脑缺血性损伤的途径,为相关药物潜在靶点的寻找和设计提供科学支撑。
英文摘要
Due to its high incidence, high mortality rates and more complications, stroke, also called the cerebral apoplexy, together with coronary heart disease and cancer is listed as three big diseases threaten to human health. Recent research data show that not only the excitotoxicity and oxidative stress, but epigenetic regulation is also involved in the process of injury and dysfunction of cerebral ischemic cell, including microRNA (miRNA). Our preliminary results show that miR-137 may be such an important miRNA during ischemia. Thus, we intend to apply for the project to solve the mechanism by which miR-137 regulate ischemic cell damage and the late cognitive dysfunction. We will elucidate: (1) the expression pattern of miRNA-137 in different periods of ischemia reperfusion, and the regulated mechanism of miRNA-137 by ischemia; (2) the key molecular that mediates the role of miRNA-137 in ischemic damage and the signal pathway of miRNA-137 regulating ischemic damage; (3) through a natural vesicles named exosome which can across the blood brain barrier efficiently, we will constructed a targeted drug delivery carrier of miRNAs and/or their inhibitors to regulate the miRNA levels in the central nervous system and treat ischemia. Based on this project, we hope to find some separate branch of miRNA signaling, in which miRNA has a direct role in regulating ischemic damage, demonstrating their value as a potential therapeutic target for the treatment of ischemia, and providing new biology experimental evidence for drug design.
