基于气化精、精生髓理论的补益脾胃元气方药调控记忆关键通路及海马神经再生的益智机制

益智中草药为老年性痴呆(AD)防治带来了新希望。然而中药的益智机制并不明确，不同理论指导下的方药益智药效尚有争议。研究者在前一项基金中提出“脑髓空虚，痰浊蒙窍”是AD的关键病机，发现补气化痰之洗心汤方能显著改善动物学习记忆能力，其作用与神经保护有关。那么，该方中不同类别药物的益智作用有何区别，其深层机制如何？仍待深究。为此，在“气化精、精生髓”理论启示下，本项目拟拆方研究并设想：补益脾胃元气类方药可能通过调控学习记忆关键通路、细胞存活及海马神经再生而在益智药效中发挥更重要的作用。为验证假说，项目拟在前期基础上，采用分子生物学等方法，从关键脑区形态功能的变化，探讨补益脾胃元气方药的益智效应；从cAMP/PKA/CREB 通路上下游调节因子变化、细胞存活及海马神经元再生角度，探讨其益智作用机制。研究将对中医“气化精，精生髓”理论的科学内涵作出新的阐释，为AD防治提供新的思路。

Nootropic Chinese herbs bring new hope for treating Alzheimer's disease(AD). However, the nootropic mechanism of herbs is not clear and nootropic effect of herbs on the basis of different theories is still controversial. The researcher proposed that brain emptiness and turbid phlegm clouding orifices are the major pathogenesis of AD in his last National Nature Science Fund Project. He discovered that Xixin Decoction can obviously improve the ability of learning and memory in experimental animals and its mechanism is related to nerve protection. Thus, what are the different nootropic effects of different herbs in Xixin Decoction and its deep mechanism? Therefore, with the guidance of qi promoting essence and essence producing marrow theory this project assumes and arises: the nootropic function of tonifying spleen-stomach and qi prescription and herbs has influences on the key signaling pathways of learning and memory, cell survival and neurogenesis of hippocampus. Molecular biological methods and other methods were adopted to verify the hypothesis. This project will discuss the nootropic effects of tonifying spleen-stomach and qi herbs on the respects of the morphologic and functional changes of brain and explore its nootropic effects from the aspects of changes in regulatory factors of the upstream and downstream cAMP/PKA/CREB pathways, cell survival and neurogenesis of hippocampus. This study will give the new explanation of scientific connotation of qi promoting essence and essence producing marrow theory and provide new insights into the prevention and treatment of AD.