miR-181b通过P50/P65并行调控Esel、VCAM-1和ICAM-1诱导动脉粥样硬化斑块进展及不稳定性

早期识别动脉粥样硬化斑块不稳定性并干预其进展对防治脑缺血极为关键。我们研究发现，miR-181b调控斑块不稳定，且可能与内皮细胞粘附分子Esel/VCAM-1/ICAM-1及NF-κB家族成员P50/P65有关。本项目拟在in Vivo和in Vitro情况下，采用免疫荧光、基因沉默、双荧光素酶报告系统、18F-FDG PET/CT显像等多种技术结合的实验方法，阐明在斑块进展和不稳定性中，miR-181b与其下游靶基因P50/P65的调控关系，确定miR-181b通过P50/P65调控Esel/VCAM-1/ICAM-1表达、导致单核细胞聚集及诱导斑块的进展和不稳定性，讨论miR-181b-P50/P65调控粘附分子表达，诱导单核细胞聚集，最终导致斑块不稳定性的具体分子机制，通过对其中关键分子如miR-181b、P50/P65等的调控，以监测并干预不稳定斑块的进展，为防治脑卒中提供新靶点。

Early identification of unstable atherosclerotic plaque and prevent its progress is critical for cerebral ischemia. Our previous studies found that miR-181b affect the plaque instability, and speculate that it may be through regulating the adhesion molecules Esel/VCAM-1/ICAM-1 via P50/P65 heterodimer of NF-κB family. We will prove the hypothesis both in Vivo and in Vitro, with the methods such as immunofluorescence, gene silencing, the dual luciferase reporting system, 18F-FDG PET/CT imaging technology. Firstly, we will explore the effects and characters of miR-181b in the plaque progression and instability, and then detect that if P50/P65 heterodimer are the downstream target genes of miR-181b in the process. Secondly, we will study that miR-181b-P50/P65 signals enhanced monocyte aggregation and accelerate plaque instability via regulating Esel/VCAM-1/ICAM-1 signaling pathway. Thirdly, by regulating the key factors such as miR-181b, P50/P65, we will determine the best therapeutic targets to prevent the progress and instability of plaque, and thus provide clue for developing new treatment strategy for stroke.