microRNAs调控线粒体自噬减轻脊髓缺血/再灌注损伤的实验研究

项目名称： microRNAs调控线粒体自噬减轻脊髓缺血/再灌注损伤的实验研究

项目编号： No.81471267

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 师恩祎

作者单位： 中国医科大学

项目金额： 70万元

中文摘要： 缺血性脊髓损伤是胸腹主动脉瘤外科和介入治疗发生率较高的严重并发症。线粒体功能障碍在心、脑等组织缺血再灌注损伤中发挥重要作用。线粒体功能障碍可以导致细胞能量代谢障碍，损伤的线粒体可以产生过量的活性氧并启动凋亡和坏死信号途径，导致细胞死亡。线粒体自噬是一种选择性清除损伤或多余线粒体的自噬过程，对于维持细胞内线粒体的质量和数量至关重要。新近研究表明，线粒体自噬在心肌和脑组织缺血/再灌注损伤中发挥保护作用。miRNAs作为转录后调控的重要机制，也参与细胞自噬和线粒体自噬的调控。目前尚没有关于线粒体自噬在脊髓缺血/再灌注损伤中作用以及miRNAs对其调控机制的研究报告。本课题拟探讨线粒体自噬在脊髓缺血/再灌注损伤中作用及其miRNAs调控机制，并通过调控与介导线粒体自噬重要蛋白表达相关的一组miRNAs，靶向调控脊髓组织的线粒体自噬，减轻脊髓缺血/再灌注损伤，旨在探索一个全新的脊髓保护策略。

中文关键词： 主动脉外科；脊髓；缺血；微小RNA；线粒体自噬

英文摘要： Ischemic injury of spinal cords remains a devastating complication with a high incidence after surgery or endovascular repair of thoracoabdominal aneurysms. Mitochondria dysfunction plays a central role in the ischemia/reperfusion injury of myocardium and brain. Mitochondria dysfunction can disrupt energy metabolism, produce reactive oxygen species and activate proapoptotic and necrotic pathways, which induce cell death. Mitophagy is a special autophagy of selective clearance of excessive mitochondria or impaired mitochondria, which is important to maintain the quantity and quality of the mitochondria. It is indicated in the newly studies that mitophagy can induce protective effects against ischemia/reperfusion injury of heart and brain. As an important control mechanism after transcription, miRNAs contribute to the control of autophagy or mitophagy. However, it is still not known the function of mitophagy in the ischemia/reperfusion injury of spinal cords and whether miRNAs affect the activity of mitophagy in spinal cords. The current study is to investigate the protective effects of mitophagy in the ischemia/reperfusion injury of spinal cords. Further study is to attenuate the spinal cords injury by control of the activity of mitophagy with miRNAs targeted at the important proteins for inducing mitophagy. The final objective is to find a new protective strategy for ischemia/reperfusion injury of spinal cords.

英文关键词： aortic surgery;spinal cord;ischemia;miRNA;mitophagy