基于血清代谢组分析的失重性骨丢失与糖代谢交互调控研究

Bone loss and subclinical Diabetes-like are developed during long-term spaceflight. Recently, Accumulating evidence was viewed as an indication that skeletal as a microgravity sensitive organ exist mutual regulation with other tissue/organs under microgravity. In this study, we will investigate the reciprocal regulation of bone remodeling and energy metabolism by Metabonomics, microCT, molecular biological and Biochemical analysis technologies. UPLC-Q-TOF-MS method will be used to analyze the changes of serum metabolome of Tail suspension rat and reveal the possible sources and regulatory pathways of serum metabolic markers (mainly associated with energy metabolism) for simulated weightlessness effect. The serum metabolic markers will be validated in human serum of human bed rest or space flight. The expected results will provide the theoretical and experimental basis for the body biomechanical response under space weightlessness. In practice, new targets and therapeutic strategies of metabolic diseases such as diabetes, osteoporosis, obesity and others and drug development will be revealed.

空间飞行导致骨丢失和亚临床性糖尿病等已成为人类长期深空探索的重要障碍。最新研究进展认为骨骼作为机体承重和力敏感器官，能将感知的重力变化信息传递给其他组织，从而使机体适应新重力环境。本项目拟采用代谢组学、microCT检测、分子生物学和理化分析等技术研究模拟失重环境下骨重建和能量代谢的变化规律及其相互关系。通过UPLC-Q-TOF-MS技术分析尾吊模拟失重效应大鼠血清代谢组变化，筛选模拟失重效应的血清代谢标志物(能量代谢类为主)，分析其组织来源及可能的调控通路，并利用头低位卧床或空间飞行血清样本进行验证。这将为阐释空间失重环境机体生物力学响应、适应的发生发展机制提供理论基础和科学依据，也为深入了解如糖尿病、骨质疏松等代谢性疾病机制与药物研发提供新的靶标位点和治疗策略。

空间飞行导致空间适应综合症已成为人类长期深空探索的重要障碍。本项目采用代谢组学、microRNA组学、microCT检测、基因敲除和生化分析等技术研究模拟失重环境下大鼠血清的能量代谢的变化规律、循环miRNA表达差异及组织间相互作用关系。通过UPLC-Q-TOF-MS技术分析尾吊模拟失重效应大鼠血清代谢组变化，筛选出了模拟失重效应的8个血清候选代谢标志物，进一步分析出能量代谢变化可能的组织来源脂肪和肝脏组织，并分析了可能的调控通路，利用猕猴头低位卧床血清样本进行代谢组研究；代谢组与尾吊大鼠血清中miRNA组结合分析，发现涉及到的信号通路主要与神经系统相关，而且发现了miRNA-383-5p及其靶基因AQP4在尾吊大鼠中发生明显变化，利用RVG修饰的外泌体运输miRNA-383-5p到C6细胞和大鼠海马组织中可以显著抑制AQP4的表达。推测miR-383-5p和AQP4 在模拟失重导致海马功能损伤中具有重要的作用。这为阐释空间失重环境机体适应性发生发展机制提供理论基础和科学依据。