从调控ERK/MAPK信号通路探讨补肾法对阿尔茨海默病及骨质疏松症"异病同治"生物学机制研究

项目名称： 从调控ERK/MAPK信号通路探讨补肾法对阿尔茨海默病及骨质疏松症"异病同治"生物学机制研究

项目编号： No.81202652

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 刘爽

作者单位： 天津中医药大学

项目金额： 23万元

中文摘要： 阿尔茨海默病（AD）和骨质疏松症（OP）属老年退行性疾病，且均存在雌激素（E2）减少。研究表明，E2减少后所致ERK/MAPK信号通路中关键因子活化降低与两病密切相关。本课题组前期发现，补肾法中药能明显改善AD和OP临床症状，且能提高E2的含量。基于此，本研究提出ERK/MAPK信号通路可能是两病的共同病理环节，而补肾法可能是通过作用于该环节而实现"异病同治"的假说。拟通过建立AD与OP模型，以补肾法中药干预，通过不同检测方法，主要观察ERK/MAPK信号通路中关键靶点的活化表达，同时观察该通路下游与AD、OP及凋亡密切相关效应因子的变化，结合观察AD模型认知功能、OP模型骨力学改变及二者微观形态学与凋亡变化，以期探讨AD与OP的共同病理环节- - "ERK/MAPK信号通路"的作用机制，并从整体到微观逐步探索补肾法对该通路的作用途径与靶点，进一步丰富中医"异病同治"科学内涵，提升其临床应用。

中文关键词： 补肾法；ERK/MAPK信号通路；阿尔茨海默病；骨质疏松；异病同治

英文摘要： Alzheimer's disease (AD) and osteoporosis (OP) are both degenerative diseases, accompanied by estrogen (E2) decrease. It has been confirmed that lower activation of key factor in ERK/MAPK signal pathway caused by E2 decrease was closely related to the two diseases. We found that kidney-nourishing herbs in traditional Chinese medicine could obviously improve the clinical symptoms of AD and OP, and could increase E2 in the serum. On the basis of previous researches, we recognized that ERK/MAPK signal pathway was the common pathological changes in the two diseases, and hypothesized kidney-nourishing therapy might the same treatment for the two different diseases by regulating ERK/MAPK signal pathway. We give kidney-nourishing herbs to AD and OP model rats, in order to discuss the mechanism of ERK/MAPK signal pathway and find the action pathway and the targets of kidney-nourishing therapy in the two diseases through observing many key indicators. This research will explore scientific connotation of "the same treatment for different diseases" and promote its clinical application.

英文关键词： kidney-nourishing therapy；ERK/MAPK signal pathway；Alzheimer's Disease(AD)；Osteoporosis(OP)；the same treatment for different diseases