循环微囊泡miR-20a跨细胞通讯参与缺血后脑血管内皮损伤的机制研究

急性脑缺血期免疫防御细胞释放大量包裹microRNAs的微囊泡至循环系统中，微囊泡microRNAs可跨细胞通讯参与脑血管内皮损伤过程，但其具体调控机制尚不清楚。本课题前期提示，微囊泡miR-20a可引起缺血后脑血管内皮紧密连接结构改变和炎性损伤，抑制微囊泡miR-20a分泌，可改善脑血管内皮损伤继而对缺血性脑损伤起到保护。我们在拟脑缺血体内外模型中，观察微囊泡miR-20a对缺血后脑血管内皮紧密连接结构的损伤，研究其对靶蛋白β-catenin及下游MMP9、NF-κB信号分子的诱导作用，并考察关键蛋白NMMHC ⅡA参与微囊泡miR-20a分泌的机制，及羟基红花黄色素A影响NMMHC ⅡA抑制微囊泡miR-20a分泌的机理，期在揭示循环微囊泡miR-20a跨细胞通讯介导脑血管内皮损伤的机制，为探索介导跨细胞通讯提供中枢保护作用的药物机理提供研究思路，也为缺血性脑损伤疾病的诊治提供科学理论

During the period of acute cerebral ischemia, immune cells release a large package of circulating microvesicle containing microRNAs into the circulatory system, which participate in brain microvascular endothelial cells injury based on cell-cell communication, however, the specific regulation mechanism is still unclear. Preliminary study indicated that microvesicle miR-20a gave rise to the structural changes and inflammatory injury of brain microvascular endothelial tight junction damage induced by cerebral ischemia, while inhibiting the secretion of microvesicle miR-20a could attenuate brain microvascular endothelial cells injury then lead to the neuroprotection for cerebral ischemia damage. Based on the cerebral ischemia in vivo and in vitro model, we would expect to observe microvesicle miR-20a functions connected to the tight junction structural damage of brain microvascular endothelial cells, monitor its functions on target protein β-catenin and the inductions on downstream MMP9, NF-κB signaling molecules, meanwhile investigate the key protein NMMHC ⅡA effects on the secretion of microvesicle miR-20a and how hydroxysafflor yellow A regulate microvesicle miR-20a secretion by influencing NMMHC ⅡA. Our studies hoped to reveal biological cell-cell communication of circulating microvesicle miR-20a in mediating brain microvascular endothelial cells injury after cerebral ischemia, providing research ideas for exploring drug mechanism in exerting neuroprotective effects based on cell-cell communication, also providing scientific theory for diagnosis and treatment of cerebral ischemia injury diseases.