早期运动干预促进脑缺血再灌注损伤神经功能恢复的线粒体机制

Numerous reports and studies have suggested exercises contribute to improved post-ischemic recovery of brain function. However, the exact mechanism underlying the effect of early exercise on improving injury recovery is still unclear. Previous studies showed early exercises resulted in a temporal increase in mtDNA, expression of mitochondrial-specific transcription factors and the mitochondrial proteins, which is followed with improved behavioral performance and reduced lesion volume. The results indicated that mitochondria maybe very immportant for the process. The project will study the role of mitochondria in early exercises induced repairing mechanisms of the brain. Firstly, we will analyze exercise induced changes in mitochondrial biogenesis and function after brain injury. Secondly, we will observe brain function recovery through detecting axonal regeneration and neurotransmitter release after injury. Lastly, antisence oligonucleotides technology will be used to confirm that early exercise protects the brain from ischemia induced injury via regulation of mitochondrial biogenesis and function. The progress of this study is expected to provide new ideas for ischemic stroke treatment and provide a theoretical basis for early exercise intervention clinical application.

大量基础与临床研究表明运动干预可有效改善卒中患者神经功能恢复。但关于早期运动干预（缺血24小时后介入）对于脑缺血损伤修复的作用及其机制尚存异议。课题组前期研究结果发现早期运动可明显促进脑缺血损伤大鼠神经行为学功能改善、减少损伤面积，同时伴有线粒体转录相关因子及标志蛋白表达改变，表明早期运动干预可促进脑损伤后神经损伤修复和行为功能恢复，且线粒体在此过程可能发挥重要作用。故本项目试从线粒体角度阐明早期运动干预促进缺血再灌注损伤修复机制。观察早期运动干预对线粒体生物合成及功能的改善，并通过细胞外液神经递质释放与轴突再生反映神经功能恢复情况；反义寡核苷酸技术分析线粒体改变与神经递质释放、轴突再生间的关系来验证线粒体在早期运动促进缺血损伤神经功能恢复机制中的重要作用，为进一步完善早期运动干预促进脑缺血再灌损伤脑保护机制提供基础，为早期运动作临床治疗手段提供理论依据，为缺血性脑卒中临床治疗提供新思路。

大量基础与临床研究表明运动干预可有效改善卒中患者神经功能恢复。课题组前期研究结果发现早期运动可明显促进脑缺血损伤大鼠神经行为学功能改善、减少损伤面积，同时伴有线粒体转录相关因子及标志蛋白表达改变，表明早期运动干预可促进脑损伤后神经损伤修复和行为功能恢复，且线粒体在此过程可能发挥重要作用。故本项目试从线粒体角度阐明早期运动干预促进缺血再灌注损伤修复机制。本研究结果进一步证实了运功训练干预可以调节缺血模型中脑组织中线粒体动态平衡及功能，促进内皮素表达及脑血流增加，减少神经细胞凋亡促进血管再生，以及促进葡萄糖代谢相关因子表达，进而完成对缺血损伤的脑保护作用。本项目成果为进一步完善早期运动干预促进脑缺血再灌损伤脑保护机制提供基础，为早期运动作临床治疗手段提供理论依据，为缺血性脑卒中临床治疗提供新思路。