基于Toll样受体通路的益气活血方“脑心同治”分子机理研究

Studying and revealing pathological features and biological basis of brain damage to heart, heart damage to brain is one of the key scientific problems of 'Treatment both brain and heart' for the brain and heart pathology involvement and prognosis in cardiovascular and cerebrovascular diseases. So, how to identify and confirm the brain and heart common imbalances in specific molecular mechanisms is interpretation the role of the characteristics and scientific expression of traditional Chinese medicine compound 'Treatment both brain and heart' ? Based on the above considerations, the project is core to study the brain and heart common imbalances in specific molecular mechanisms in different pathology status (cerebral /myocardial ischemia) under the same body condition. Guided by 'Treatment both brain and heart' concept, the replenishing qi and promoting blood circulation recipe (representative recipe Naoxintong) is selected to be as 'probe', using a variety of pathological models (cerebral ischemia, myocardial ischemia models and nerve cell and cardiac cell models by hydrogen peroxide injury from organs , molecules and cells three levels, to study the relationship between the role of under the same body condition brain damage to heart, heart damage to brain and Toll-like receptor-related pathways.The project is aim to definite the replenishing qi and promoting blood circulation recipe’s brain, heart common treatment utility characteristics and mechanism of action, and to interpret Toll-like receptor mediated signal transduction pathways related change is one of the key scientific problems of 'Treatment both brain and heart' , and to provided novel ideas and novel strategies to 'Treatment both brain and heart' theoretical study.

心脑血管疾病脑、心之间存在着病理累及及相互转归，研究并揭示脑损及心、心损及脑的病理作用特点和生物学基础，是“脑心同治”的关键科学问题之一。那么如何辨识、确认脑、心共同的失衡特定分子机制，阐释中药复方“脑心同治”的作用特点和科学表达呢？基于以上考虑，本项目拟以不同病理状态（脑/心肌缺血）同一机体条件下脑、心共同的失衡特定分子机制为研究核心，以“脑心同治”为指导理念，选取益气活血方（代表方药脑心通方）为“探针”，采用多种病理模型（脑缺血模型、心肌缺血模型以及过氧化氢损伤的神经细胞、心肌细胞模型）结合组学技术和方法，从器官、细胞、分子三个水平，考察药物对同一机体脑损及心、心损及脑的作用与Toll样受体相关通路的关系，以期明确益气活血方脑、心同治效用特点及作用机制，阐释Toll样受体介导的细胞信号转导相关通路变化是“脑心同治”的分子生物学基础之一，为“脑心同治”理论的研究提供新思路和新策略。

心脑血管疾病脑、心之间存在着病理累及及相互转归，研究并揭示脑损及心、心损及脑的病理作用特点和生物学基础，是“脑心同治”的关键科学问题之一。本项目依托不同病理状态（脑/心肌缺血），选取益气活血方（代表方药脑心通方）为“探针”，应用组学技术和方法，从器官、细胞、分子三个水平，考察药物对同一机体脑损及心、心损及脑作用与Toll样受体相关通路、蛋白的关系，以期明确益气活血方脑、心同治效用特点及作用机制。. 基于此，本项目首先观察脑缺血后不同时间点（6h、12h、24h、36h、72h）和心肌缺血后不同时间点（6h、24h、72h、7d、14d）脑、心器官功能的变化情况，筛选出脑缺血（脑损及心）的时间点在24h及以后，心肌缺血（心损及脑）的时间点则在72h及以后。其次，选取益气活血方（代表方药脑心通方）为“探针”，应用组学技术和方法，考察药物对同一机体脑损及心、心损及脑作用与Toll样受体相关通路、蛋白的关系，发现脑缺血状态下，MAPK、PI3K-Akt、Toll样受体通路是脑心通方涉及的脑心同治信号通路；心肌缺血状态下，NOD样受体信号通路、RIG-I样受体信号通路、Toll样受体信号通路是脑心通方涉及脑心同治信号通路，脑缺血、心肌缺血共有脑心通方涉及的脑心同治信号通路是Toll样受体信号通路；Toll样受体通路相关蛋白IRF-3、TLR2、TLR7、TNF-α这四个蛋白是脑缺血和心肌缺血状态下脑心通方涉及到的“脑心同治”相关蛋白；最后明确了脑心通方干预脑缺血（脑损及心）与TLR2、MyD88、NF-κB、MAPK、AKT、mTOR、PIK3、TBK1、BCl等9个蛋白相关；脑心通方干预心肌缺血（心损及脑）与TIMM10、MYH6、GAK、NDUFB9、ATP5O、SYNPO2I、MAVS、GPSM1、TLR7、MyD88等10个蛋白相关。