自噬在模拟失重诱导的心功能失调和心肌萎缩中的作用

Sustained exposure to micro-gravity in space may cause cardiac dysfunction and atrophy, but the exact mechanism governing the regulation of myocardial dysfunction and cardiac atrophy remains poorly understood. Autophagy, a pathway of protein degradation, has recently been shown to be involved in the regulation of cardiac dysfunction and atrophy. In our experiments, we found that weightlessness induced dysfunction, atrophy and up-regulating the activity of autophagy in rat cardiac tissue. Using the tail suspension model to simulate weightlessness, we found that cardiac function, especially contractility, and the area of the cardiac atrophy declined in the cardiac tissue. Additionally, cross-sectional area of myocardial cell shrunk, likewise the expression of autophagy-related proteins were elevated in the atrophic cardiac tissue. . In this project, we will further explore the regulation of autophagy on simulate weightlessness. Whether inhibition of autophagy with the inhibitor of autophagic could recovered the systolic function reduced by tail suspension treatment. To determine if increased cell apoptosis also plays a role in cardiac atrophy under simulate weightlessness, which might be regulated by autopagy. In fine, we will verify the effects of autopagy on cardiac dysfunction and atrophy under simulated weightlessness by simulated microgravity induced by clinostat on myocardial cells. This study will promote us to understand the mechanisms of cardiac dysfunction and atrophy under weightlessnessand, and disclose a new therapeutic target.

长期失重可诱导机体心功能失调和心肌萎缩，是限制载人航天发展的重要因素之一。自噬蛋白降解信号通路参与心肌萎缩和心功能失调进程，但该通路在失重对心血管影响中至今未见报道。我们前期实验结果表明，长期尾吊模拟失重大鼠心功能显著降低、心肌细胞发生萎缩，而且心肌细胞自噬活性显著增强，提示自噬活化可能参与了尾吊诱导的大鼠心功能失调和心肌萎缩进程。. 本课题拟在前期工作基础上，采用大鼠尾吊失重模型和大鼠原代心肌细胞回转失重模型，通过分析心肌细胞自噬活性的变化规律，检测选择性抑制自噬过度活化后尾吊大鼠心功能失调、心肌萎缩和心肌细胞凋亡的变化，揭示自噬在模拟失重所致心功能失调和心肌萎缩中的调控作用及其作用方式。该研究将加深对失重诱导的心功能失调和心肌萎缩发病机制的认识，为其预防和治疗提供新的靶点。

长期失重可诱导机体心功能失调和心肌萎缩，是限制载人航天发展的重要因素之一。自噬蛋白降解信号通路参与心肌萎缩和心功能失调进程，但该通路在失重对心血管影响中至今未见报道。. 本项目采用大鼠尾吊失重模型和大鼠原代心肌细胞回转失重模型，通过分析心肌细胞自噬活性的变化规律，检测选择性抑制自噬过度活化后尾吊大鼠心功能失调、心肌萎缩和心肌细胞凋亡的变化。实验结果表明，长期模拟失重后大鼠心肌细胞功能显著降低、细胞减小萎缩，自噬活性显著增强，选择性抑制模拟失重诱导的心肌细胞自噬过度活化能够显著改善心肌细胞功能。证实自噬活化参与了尾吊模拟失重和回转模拟失重诱导的大鼠心功能失调和心肌萎缩进程，自噬信号通路关键蛋白可能作为潜在的航天失重心血管功能失调的预防和治疗新靶点。