失重引起的机体心血管功能失调是制约长期载人航天飞行的重要因素，血管内皮细胞功能异常在失重后心血管失调中扮演重要角色，但其机理尚未明确。膜-骨架连接蛋白moesin已证实在调控细胞骨架分布和细胞功能中发挥重要作用。我课题组前期研究发现，模拟失重可致moesin上游调控分子RhoA/ROCK活性增强，证实失重所致的动脉收缩功能异常与RhoA活性增强有关。据此我们推测，RhoA/ROCK介导moesin活性增高可能是调控失重后内皮细胞功能异常的重要通路。本课题拟在前期研究基础上，以大血管和微血管内皮细胞为研究对象，应用细胞及动物模拟失重模型，探讨模拟失重致内皮细胞功能异常的变化规律，揭示meosin在失重后内皮细胞骨架分布异常及功能改变中的作用，阐明模拟失重致内皮细胞meosin异常表达的分子机制。该结果有助于完善失重致血管内皮细胞功能变化的可能机制，为防护失重致机体心血管功能失调提供新的依据。

The cardiovascular dysfunction induced by microgravity is thought to represent one of the dangers of long term spaceflight. It has been shown that changes of endothelial cells function appear to be play important role in cardiovascular deconditioning. Yet, the cellular and molecular mechanism underlying it remains to be fully elucidated. Moesin is emerging as the potential candidate that likely to mediate this process. Serving as cross-linkers between actin filaments and plasma membrane, moesin is engaged in cytoskeleton redistribution and cell functions. Our previous study shows that altered expression and activity of RhoA/ROCK may play important roles in the increased vasoconstriction of thoracic aorta induced by simulated microgravity in rats. Differences of the thoracic aortic vasoconstriction between simulatedm icrogravity and normal rats could be eliminated by inhibition of ROCK. Therefore, we presume the RhoA-ROCK-dependent moesin phosphoryaltion is involved in endothelium dysfunctions induced by simulated microgravity. In this study, we will use the clinostat and tail-suspended rats to simulate microgravity. The aim of this study is to explore the changes of endothelial cells function induced by simulated microgravity, and further to elucidate the role of moesin in regulating cytoskeleton distribution and cell functions after microgravity exposure and the mechanisms underlying it. Our finding might help to know the possible mechanism of the endothelium dysfunctions induced by microgravity and provide some theoretical basis to the protection of postflight cardiovasucular dysfunctions.

失重环境引起的航天员心血管功能失调涉及多种机制，研究发现，模拟失重后血管系统的改变在其中扮演重要角色，内皮细胞对重力高度敏感，失重环境可引起内皮细胞出现功能及结构改变，然而其调控机制尚不清楚。Moesin是一种膜-骨架连接蛋白，在内皮细胞的多种功能调控中发挥重要作用。本研究首先以内皮细胞为研究对象，利用细胞回转器模拟失重效应，观察了模拟失重对内皮细胞功能和细胞骨架的影响，明确了细胞骨架在细胞功能改变中的调节作用，研究了模拟失重对内皮细胞RhoA、ROCK2、Moesin表达的影响，进一步研究发现，模拟失重引起的内皮细胞功能改变与RhoA、ROCK2和Moesin活性异常有关。继而，以大鼠为研究对象，观察了RhoA在模拟失重大鼠不同部位动脉中的表达及在血管功能改变中的作用。结果发现：1. 模拟失重可引起体外培养的血管内皮细胞发生结构及功能的改变。表现为模拟失重可引起内皮细胞细胞面积减小、增殖受抑、细胞周期受阻以及迁移、体外血管生成能力的增加。2. 模拟失重可引起血管内皮细胞出现细胞骨架的改变，表现为模拟失重可使内皮细胞微管的放射状结构被破坏，呈现弥散性改变，应力纤维总量减少，G-actin/F-actin比例显著升高；利用细胞骨架稳定剂可消除模拟失重引起的细胞迁移和血管生成能力的异常。3. 模拟失重24h可引起内皮细胞RhoA、ROCK2、Moesin活性降低，改变三者的活性可逆转模拟失重引起的内皮细胞迁移和血管生成能力的异常。4. 大鼠模拟失重28d可引起不同部位血管RhoA和Rock2表达发生差异改变，表现为在颈总动脉中RhoA和ROCK2表达下降而肠系膜动脉中两种蛋白的表达升高，改变ROCK2的活性可以部分逆转模拟失重引起的血管收缩能力的改变。该结果将有助于完善失重致血管内皮细胞功能变化的可能机制，为失重致机体心血管功能失调的防护提供新的理论依据。