MicroRNAs与组蛋白去乙酰化酶HDACs共同调控脑卒中后缺血区脑组织血管新生的分子机制

脑卒中可诱发缺血区的血管新生，新生血管的密度与患者的预后密切相关。因此，有效促进新生血管的形成对于脑卒中等缺血性疾病的恢复至关重要。课题组前期研究发现miRNA210参与了缺氧/ HIF-VEGF-Notch信号通路调控脑缺血后血管新生过程，同时还发现脑缺血后，与血管生成密切相关的miRNA222、92a等表达水平均出现明显变化并伴随多种组蛋白乙酰化酶HDACs的表达变化。结合组蛋白修饰与miRNA存在相互调控关系的最新研究报道，我们推测极有可能是组蛋白乙酰化与miRNA共同参与了脑缺血后血管新生的调控。本课题通过Solexa高通量测序、质谱分析及基因芯片等技术筛选调控脑缺血后血管新生的关键miRNAs和HDACs，并对二者之间相互调控的关系及调控环节进行研究验证，以期阐明miRNAs与组蛋白修饰为主构成的表观遗传调控网络调控脑卒中后血管新生的新机制，为脑卒中的修复治疗提供新的科学依据。

Ischemic stroke can induce angiogenesis in the ischemic area, and the density of new blood vessels is closely related to the prognosis of patients. Promoting angiogenesis effectively is essential to the recovery of stroke and other ischemic diseases. Our preliminary studies indicate that miRNA210 participates in angiogenesis process through HIF-VEGF-Notch pathway. We also found that expressions of miRNA222 and miRNA92a, which were closely related to angiogenesis, changed significantly after stroke. Simultaneously, expressions of a variety of HDACs changed distinctly, too. Combine our data with recent studies about complex and mutual relationships between histone modification and miRNA, we proposed that histone acetylation could cooperate with miRNA in modulating angiogenesis after stroke. This project intends to find out the key miRNAs and HDACs in angiogenesis after stroke through Solexa high-throughput sequencing, MS analysis and genechip, and verify their mutual regulation relationships and important regulation steps. The purpose of this research is to preliminarily clarify the new mechanisms based on the modulation network mainly composed of miRNA and histone modification in angiogenesis after stroke, and provide new scientific evidence for new targets of brain stroke treatment.