模拟失重对内皮依赖性血管生成的影响及微囊/微囊蛋白-1（Caveolae/Caveolin-1）在其中的调控作用研究

内皮细胞（ECs）作为机体血管壁的衬里对重力变化极为敏感，研究显示失重/模拟失重可以影响ECs的多种功能，但有关它对内皮依赖性血管生成能力的影响始终未被系统探究。微囊（Caveolae）及其标志性蛋白微囊蛋白-1（Caveolin-1）在血管内皮分布广泛，Caveolae作为ECs质膜的微小结构域，一方面感知失重/模拟失重引起的血流动力学改变，另一方面将力学信号转换为生物化学信号来调节心血管系统的多种功能。因此，本项目将综合重力生理学研究手段、分子生物学方法、细胞培养、基因敲除动物、血管环体外培养、细胞转染技术等，从离体和在体多个水平探讨Caveolae/Caveolin-1 在模拟失重所致的内皮依赖性血管生成能力改变中的作用及调控机制。本项申请可深化对失重致血管内皮功能改变机制的理解，丰富空间医学领域与其相关的基础理论，为今后长期载人航天飞行中血管生成性疾病的研究提供有价值的参考和借鉴。

Endothelial cells (ECs) are extremely sensitive to gravity changes as the lining of the vessel wall of the body. Studies have shown that weightlessness/simulated weightlessness can affect various functions of ECs, but there is little exploration for its impact on endothelium-dependent angiogenesis capacity. Caveolae and its iconic protein caveolin-1 are widely distributed in vascular endothelium. As the tiny structural domain of ECs plasma membrane, on the one hand, caveolae could perceive the hemodynamic changes caused by weightlessness/simulate weightlessness. On the other hand, it plays various roles in converting the mechanical signal to biochemical signal for the regulation of cardiovascular system. Therefore, the project will integrate gravity physiology research tools, molecular biology method, cell culture, gene knockout animals, in vitro culture of vascular rings, and cell transfection technology, to explore the role caveolae/caveolin-1 playing in the changes of endothelium-dependent angiogenesis capacity caused by simulated weightlessness as well as its regulation mechanism from both in vitro and in vivo levels. This application can deepen the understanding of mechanism change by vascular endothelial function due to weightlessness, and enrich basic theories of associated space medical domain, thus to provide valuable reference for the research of angiogenic diseases in long-term manned space flight in the future.