缺氧缺血诱导血管内皮前体细胞源性microvesicle促进血管生成的机制研究

It is important to study the effective mechanisms to repair hypoxic-ischemic brain injury. Preliminary research found that endothelial progenitor cell-derived microvesicles (EPC-MV) could promote the proliferation of endothelial cells, reduce the injury area damaged by hypoxic-ischemia, and improve the blood perfusion. We also found that the expression of PTEN was decreased, while the expression of miR-372 was increased. These results indicated that miR-372 in EPC-MV induced by hypoxic-ischemia probably modulate the angiogenesis through PTEN signaling pathway and the downstream signaling molecules. In this study, on the basis of our previous work, we will discuss the changes of the biologic characteristics of EPC-MV after hypoxic-ischemic induction, and identify the regulatory role in angiogenesis. We will further clarify the biologic characteristics of miR-372, and deeply explore the mechanisms of miR-372 modulating angiogenesis through PTEN signaling pathway by using the gene over-expression and silence-expression technology. This study will help us to find a new potential intervention for hypoxic-ischemic brain damage.

探索发育期脑缺血缺氧损伤的有效修复机制具有重要的意义。前期研究发现经过缺氧缺血诱导后，血管内皮前体细胞源性microvesicle（EPC-MV）可促进血管内皮细胞增殖，并可减轻脑损伤并且改善血流灌注，并发现血管内皮细胞中PTEN表达下调、miR-372表达上调，提示缺氧缺血诱导后EPC-MV中的miR-372可能通过PTEN及下游信号通路实现对血管生成的调控。本课题将在前期工作基础上，探讨缺氧缺血诱导后，EPC-MV生物学特征的变化，证实其对调控血管内皮细胞调控血管生成的作用，并探讨miR-372的生物学特征，通过过表达和沉默表达，观察miR-372对血管生成相关指标的影响，以及PTEN及下游相关信号通路的影响，探讨EPC-MV促进脑缺血缺氧损伤修复的机制，本研究具有源头创新性，将为缺氧缺血脑损伤的治疗提供新的线索。