整合素介导的血流应力相关炎症反应对于促进颅内动脉瘤生长和破裂的作用及相关机制研究

颅内动脉瘤严重危害人群健康，但其生长和破裂的机制尚未阐明。我们既往研究阐述血流应力和颅内动脉瘤破裂密切相关（2014），并发现整合素（Integrin）在破裂和未破裂动脉瘤间可能存在差异。本课题拟探索整合素在动脉瘤进展中的作用和机制。整合素是一种跨膜蛋白，能介导细胞内外力学信号传递，参与炎症应答等过程。本课题拟收集颅内动脉瘤样本及影像资料，分析血流动力学特点，并检测整合素及相关分子的表达情况。将小鼠脑血管内皮细胞于不同血流应力环境中培养，运用敲低和过表达的方法构建细胞模型，以NFκB通路为切入点，阐明整合素介导的血流应力相关炎症反应在促进动脉瘤进展中的可能机制。对血流动力学颅内动脉瘤大鼠模型进行药物干预，明确整合素表达异常对于促进动脉瘤进展的作用。本课题将证实“整合素介导的血流应力相关炎症会导致血管内皮抗血流应力能力降低，从而促进颅内动脉瘤生长和破裂”的假说，为颅内动脉瘤的防治提新思路。

Intracranial aneurysm (IA) is a harmful disease, however the mechanism of growth and rupture of IA is still unknown. Our previous study demonstrated the relationship between biological stress and IA rupture (2014), and found the potential expressing difference of integrin between ruptured and unruptured IAs. The aim of this study is to explore the role of integrin in development of IAs and relevant mechanisms. The integrin is a transmembrane protein, which can mediate mechanical signal transfer inside and outside the cells and trigger the process of inflammatory response and so on. This study will collect the sample of IAs and radiological data to investigate the hemodynamic characteristics and detect the expression of integrin and relevant molecules. Mouse brain microvascular endothelial cells will be cultured under different flow stress. Knockdown and overexpression methods will be used to construct cell models. Taking NFκB pathway as a breakthrough point, this study will elucidate the role of stress-related inflammation mediated by integrin-NFκB pathway in development of IAs. The hemodynamic IA rat model will be treated with relevant medicine in order to verify that the abnormal expression of integrin can promote the development of IAs. This study will confirm the hypothesis that "stress-related inflammatory mediated by integrin will reduce the ability of vascular endothelia to resist biological stress, thus promoting the growth and rupture of intracranial aneurysms", which will provide new targets for the prevention and treatment of IAs.