跑步训练对老年大脑白质毛细血管的作用及机制研究

Using the three-dimensional stereological methods, we have for the first time in the world obtained the following findings. 1. The age-related atrophy of white matter was mainly due to the changes of the myelinated fibers in the aged white matter. 2. There was significant decline in the capillaries of aged white matter. 3. There were significant protective effects of running exercise on the aged white matter and the myelinated fibers of aged white matter. The blood supply of aged white matter was significantly decreased and the myelin-formed cells, oligodendrocytes, were very sensitive to the deficiency in blood supply and oxygen. Whether did running exercise protects the aged white matter through the improvement of the blood supply in aged white matter? Until now, there have been no studies in the world regarding the effects of running exercise on the capillaries of aged white matter and the mechanisms of these effects, the relationship between the effects of running exercise on the capillaries in aged white matter and the effects of running exercise on the aged white matter and the myelinated fibers in aged white matter. To answer these questions has very important value for understanding the mechanisms of the protective effects of running exercise on aged white matter. Therefore, in the current project, we plan to use behavioral methods, immunohistochemical methods, transmission electron microscope techniques, stereological methods and molecular biological methods to study the effects of running exercise on the capillaries in aged white matter and the mechanisms of these effects. The results obtained in the present project will be very helpful for further understanding the structural and molecular bases of the effects of running exercise on aged brain, which will provide very important scientific bases for exploring the drugs and behavioral means to delay the aging process of brain.

我们在国际上首次运用三维定量的体视学方法发现：①老年大脑白质萎缩主要是由于有髓神经纤维改变所致；②白质内毛细血管存在显著性老年改变；③跑步训练对老年大脑白质及白质内有髓神经纤维具有积极的保护作用。老年大脑白质的血供显著性下降，而髓鞘形成细胞（少突胶质细胞）对缺血缺氧很敏感。跑步训练是否是通过改善老年大脑白质的血供而实现对老年大脑白质的保护作用呢？跑步训练对老年大脑白质毛细血管的作用及机制，以及这些作用与跑步训练对老年大脑白质及白质内有髓神经纤维作用的关系，国内、外尚未见研究报道。而回答这些问题对认识跑步训练保护老年大脑白质的机制具有重要的科学意义。因此，我们拟运用行为学、免疫组织化学、电镜技术、体视学和分子生物学等方法研究跑步训练对老年大脑白质毛细血管的作用及机制，以期进一步认识跑步训练对老年大脑功能作用的结构和分子生物学基础，从而为寻找缓解大脑衰老进程的各种药物和行为学手段提供科学依据。

老年大脑白质的血供显著性下降，跑步训练是否是通过改善老年大脑白质的血供而实现对老年大脑白质的保护作用呢？跑步训练对老年大脑白质毛细血管的作用及机制，以及这些作用与跑步训练对老年大脑白质及白质内有髓神经纤维作用的关系，国内、外尚未见研究报道。因此，本项目运用行为学、免疫组织化学、电镜技术、体视学和分子生物学等方法，研究跑步训练对老年大脑白质毛细血管的作用及机制，以期进一步认识跑步训练对老年大脑功能作用的结构和分子生物学基础。我们主要的研究发现是：跑步训练对中老年和老年雌、雄性大鼠的空间学习记忆能力均具有不同程度的改善作用；短期跑步训练可以不同程度增加中老年及老年大鼠大脑白质体积、白质内有髓神经纤维总长度；短期跑步训练干预可以显著增加中老年雌、雄性大鼠白质内毛细血管的总长度；长期跑步训练干预可以显著增加老年雌、雄性大鼠大脑白质体积、白质内有髓神经纤维总长度和总体积；长期跑步训练干预可以显著增加老年雌、雄性大鼠大脑白质内毛细血管总长度、总体积和总表面积；长期跑步训练促进了外周血中BDNF的显著性升高，但使大脑白质中神经、血管生长相关因子的蛋白含量显著性降低；长期跑步训练能够显著性延缓老年雄性与雌性大鼠大脑皮质毛细血管退行性变化的进程；跑步训练可以增加大鼠大脑皮质和海马毛细血管生成，且内源性NO在跑步训练对大鼠大脑皮质和海马内毛细血管的生成中起到重要调节作用。这些研究结果为跑步训练延缓老年大脑功能下降提供了重要的形态学基础，也为将来寻找延缓大脑衰老进程的手段提供了重要的“靶结构”和“靶分子”。