LncRNA RGD1562465介导运动训练促进脑梗死后星形胶质细胞向神经元传递线粒体的作用机制

脑缺血引起线粒体损伤导致神经元能量耗竭后死亡，近来发现星形胶质细胞可向缺血神经元传递线粒体，恢复其供能，从而减少死亡，但机制未明。我们前期研究证实运动训练可抑制自噬减少神经元死亡。预实验结果显示：①运动训练促进高血压大鼠脑梗死后星形胶质细胞向神经元传递线粒体，增加神经元存活；②运动训练减少梗死后星形胶质细胞线粒体过度自噬后丢失，上调线粒体传递关键分子CD38表达；③高通量测序发现运动训练显著下调星形胶质细胞中lncRNA RGD1562465表达，释放miR-326-5p，抑制线粒体自噬，上调CD38表达。据此，我们提出科学假说：运动训练下调高血压大鼠星形胶质细胞中RGD1562465表达，促进梗死后星形胶质细胞向神经元传递线粒体，增加神经元存活。本项目将深入阐释RGD1562465介导运动训练保护高血压脑梗死后神经功能的作用机制，研究结果将为运动训练改善高血压脑梗死后神经功能提供新依据。

Ischemia-induced mitochondrial damage leads to neuronal energy depletion, which is the key to neuronal death. Recently, it has been found that astrocytes can reduce neuron death by delivering mitochondria to neurons, but the mechanism is unclear. Our previous articles demonstrated that exercise training inhibits autophagy and reduces neuronal death. In our recent results, exercise promoted transfer of mitochondria from astrocytes to neurons after cerebral infarction in hypertensive rats and increases neuron survival. Exercise reduced the loss of astrocyte mitochondria after attenuating autophagy and up-regulated CD38 expression. High-throughput sequencing revealed that exercise training significantly reduced the expression of lncRNA RGD1562465 in astrocytes, released miR-326-5p, down-regulated mitophagy related proteins, and up-regulated CD38 expression. In summary, we propose a scientific hypothesis that exercise down-regulates the RGD1562465 expression in astrocytes of hypertensive rats, promotes the delivery of mitochondria to neurons and increases neuron survival after ischemic infarct. This project will explore the mechanism of RGD1562465-mediated exercise training to protect neurological function after cerebral infarction in hypertensive rats. The research results will provide a new basis for exercise training as an intervention for cerebral infarction in hypertensive rats.