平滑肌细胞Ryanodine受体介导的内质网应激与线粒体氧化应激在模拟失重大鼠脑动脉炎性反应中的作用及其机制研究

航天失重环境所引起的脑动脉功能与结构重建是航天员“心血管功能失调”的重要因素，其发生机理目前仍不甚清楚，也缺乏有效的对抗措施。前期已证实模拟失重可引起脑动脉发生炎性反应，但重力信号是如何转化为炎症刺激信号，国内外还未见报道。我们最新工作发现：模拟失重可增强Ryanodine受体（RyR）活性，且RyR可通过激活内质网与线粒体氧化应激信号促进炎性反应，我们还筛选出4个力学敏感性LncRNA可能作为其潜在的上游调控分子。结果提示：平滑肌细胞RyR通道可感受重力信号，通过内质网与线粒体氧化应激参与模拟失重大鼠脑动脉炎性反应与脑动脉重建。本项目拟采用电生理学、分子生物学、血管体外培养、细胞转染等技术从整体、器官、细胞与基因等多个水平探讨RyR通道介导的内质网应激与线粒体氧化应激在模拟失重大鼠脑动脉炎性反应中的作用。本项目可对航天失重脑动脉的重建机制提出新的思路，并希望找到新的药物靶点作为对抗措施。

Cerebrovascular remodeling has been regarded as one of important factors which may induce postspaceflight cardiovascular dysfunction. However, the mechanism remains unknown and there are still no effective countermeasures. Our previous work has demonstrated that simulated microgravity induced the inflammatory response in rat cerebral arteries through NF-kapaB pathway. Recently, we found that simulated microgravity increased the activities of Ryanodine receptor (RyR) in cerebral vascular smooth muscle cells (VSMCs), which induced the endoplasmic reticulum stress and oxidative stress in the cerebrovascular inflammatory response of simulated microgravity rats. In addition, we have screened 4 long non-coding RNA (LncRNA), which maybe the upstream signal pathway of RyR. Our results suggested that RyR might sense the microgravity signal and then induced the endoplasmic reticulum stress and oxidative stress in the inflammatory response of rat cerebral arteries. In the present study, we want to investigate the role of RyR and its related signal pathway in the cerebrovascular inflammatory response of simulated microgravity rats with molecular biology, culture cells, and cell transformation techniques in vivo and in vitro. Our study may provide a novel mechanism for cerebrovascular remodeling during real/simulated microgravity. We also want to find a new drug target for countermeasure to ensure the health and efficiency of astronauts.