石菖蒲及其活性成分改善运动疲劳大鼠学习记忆的作用机制研究

The incidence of fatigue caused by exercise is more and more with the improvement of the level of competitive sports, the rise of public fitness and life rhythm speeding up. Numerous studies have confirmed that the body’s learning and memory ability is decreased obviously when the body is in a state of fatigue. The methods of improving the body’s learning and memory with fatigue are less. Our studies shows that acorus tatarinowii Schott and its active constituents (alpha-asarone and 5-hydroxymethyl furfural) can significantly improve the learning and memory ability of rats with fatigue caused by exercise. So using the model of rats with fatigue caused by exercise, this project is to study the concentration-response relationship of acorus tatarinowii Schott and its active constituents improving learning and memory ability of rats with fatigue caused by exercise by using the methods of avoid dark experiment and water maze test, and the effects on hippocampus morphology of rats with fatigue caused by exercise by the methods of transmission electron microscopy (sem) and so on. This project is also to study acorus tatarinowii Schott and its active constituents’s the adjustment effect on RGS14 / MEK/ERK signaling pathway in hippocampus of rats with fatigue caused by exercise by the methods of using western blot (WB), real-time fluorescent quantitative PCR (RT-PCR) and immunohistochemistry techniques. Its aim is to clarify the mechanism of acorus tatarinowii Schott and its active constituents’s improving learning and memory ability of rats with fatigue caused by exercise. This is likely to find new targets of acorus tatarinowii Schott and its active constituents’s improving learning and memory ability. It also is likely to find the lead compounds of improving learning and memory of the bodies with fatigue caused by exercise. It will have broad prospect of application.

随着竞技运动水平的提高，大众健身热的兴起和生活节奏的加快，运动疲劳的发生率越来越高。大量研究证实，当机体处于疲劳状态时，其学习记忆能力明显降低。目前能提高疲劳机体学习记忆的方法较少。项目组研究表明石菖蒲及其活性成分（α-细辛醚和5-羟甲基糠醛）能明显提高运动疲劳大鼠的学习记忆能力。因此本项目拟采用运动疲劳大鼠模型，应用避暗实验与水迷宫实验和透射电镜等方法，研究石菖蒲及其活性成分改善运动疲劳大鼠学习记忆的量效关系和对海马的形态学影响；应用免疫印迹、实时定量PCR和荧光免疫组织化学等技术研究石菖蒲及其活性成分对运动疲劳大鼠海马RGS14/MEK/ERK信号转导通路的调节作用。旨在阐明石菖蒲及其活性成分改善运动疲劳机体学习记忆的作用机制。将有可能发现石菖蒲及其活性成分改善学习记忆的新的作用靶标，寻找到改善运动疲劳机体学习记忆的先导化合物，必将具有广阔的应用前景。

随着竞技运动水平的提高，大众健身热的兴起和生活节奏的加快，运动疲劳的发生率越来越高。目前大量研究证实，当机体处于疲劳状态时，其大脑的学习、记忆功能受到明显的影响。学习记忆能力又是从事日常工作生活以及竞技体育的重要基础。目前能有效提高疲劳机体学习记忆的方法较少。本研究首次表明石菖蒲提取物及其活性成分5-羟甲基糠醛和α-细辛醚具有一定的抵抗运动疲劳所致大鼠学习记忆的下降，能在一定程度上缓解运动疲劳对海马神经元细胞所产生的病理改变，抵抗运动疲劳所致海马树突的损伤。并呈一定的剂量依赖性。且α-细辛醚的作用效果强于5-羟甲基糠醛。其作用机制研究结果表明：石菖蒲及其活性成分-5-羟甲基糠醛能显著提高海马p-ERK1/2和p-CREB蛋白表达水平。石菖蒲及其活性成分ɑ-细辛醚能明显提高海马脑组织SOD和NOS活性及n-NOS蛋白表达水平，降低MDA含量。同时石菖蒲和其活性成分α-细辛醚可通过抑制海马CA2区RGS14表达水平，从而上调信号蛋白Raf-1，ρ-MEK，ρ-ERK1/2的表达水平，显著提高脑源性营养因子BDNF的表达水平。石菖蒲和其活性成分α-细辛醚对海马CA2区RGS14/MEK/ERK信号通路的调节可能是其改善疲劳运动大鼠学习记忆的重要机制。本研究首次揭示了疲劳运动致机体学习记忆下降的重要信号作用机制，同时也部分揭示了石菖蒲及其活性成分5-羟甲基糠醛(HMF)和α-细辛醚提高运动疲劳大鼠学习记忆的作用机理，为石菖蒲在运动医学中的应用提供了重要的实验依据。同时也首次表明石菖蒲中的活性成分5-羟甲基糠醛(HMF)也是石菖蒲中改善学习记忆的重要成分，为今后应用石菖蒲提高学习记忆下降相关疾病提供了新的活性成分。