肌内皮缝隙连接介导的内皮-平滑肌间直接通讯在模拟失重后血管区域性分化中的作用及机制

失重环境可致航天员血管系统出现区域性分化改变，表现为机体上半身和下半身血管分别发生上调性及下调性改变，目前机制未明。肌内皮缝隙连接作为内皮和平滑肌细胞间特有的直接通讯方式，容许两种细胞间进行直接的电和化学信号交流，进而维持血管内环境稳态。业已证实，肌内皮缝隙连接对重力高度敏感，然而，目前关于失重/模拟失重环境下肌内皮缝隙连接的结构、分布改变及其在失重血管区域性分化改变中的作用尚未见报道。本项目在既往研究基础上，拟采用大鼠模拟失重和内皮细胞-平滑肌细胞共培养模型，在整体和细胞两个层面探讨模拟失重下肌内皮缝隙连接在机体前/后身血管的变化规律，揭示肌内皮缝隙连接在调控模拟失重后血管区域性分化改变中的作用，进而阐明内皮细胞通过肌内皮缝隙连接调控平滑肌功能的信使分子及胞内分子机制。本项目有望为揭示失重致血管区域性分化改变的机制提供新的认识，为失重后心血管功能失调的防护策略提供新的思路。

Astronauts may suffer region-specific vascular remodeling during long duration spaceflight, manifested as up-regulation and down-regulation of upper body and lower body blood vessels, respectively. However the mechanism underlying it remains unknown. As a unique direct communication mode between endothelial cells and smooth muscle cells, myo-endothelial gap junction allows direct electrical and chemical signal exchange between the two kinds of cells, thus maintaining the homeostasis of vascular environment. It has been confirmed that myo-endothelial gap junction is highly sensitive to gravity. However, there is no report about the changes of structure and distribution in myo-endothelial gap junction and its role of in alteration in vascular system induced by microgravity. Based on the previous study, we will use the tail-suspended and clinorotation to simulate microgravity to explore the changes of myo-endothelial gap junction in vascular vessels and coculture model of endothelial cell-smooth muscle cells. And further to reveal the role of MEGJ in regional alteration in vascular system induced by simulated microgravity and to elucidate the messengers and molecular mechanisms in regulating the function of smooth muscle cells. Our finding might help to know the mechanism of alteration in vascular system induced by microgravity, and provide a new idea for protective strategies of cardiovascular dysfunction after microgravity.