基于益气解毒方对炎症网络的整体调节探讨其药效-药代不关联的科学本质

A new TCM Yiqijiedu decoction had been choosen as a study object which showed a strong preliminary foundation of significant anti-cerebral ischemia efficacy and good synergism in this project.The experiment had been designed from the perspective of the overall regulation of inflammation of the central and peripheral systems network in order to clarify the scientific nature of the pharmacokinetic and pharmacodynamic disconnection of this prescription in which the three main component was characterized as Weak lipophilicity，difficulty to penetrate the blood-brain barrier，poor drug absorption，and low oral bioavailability. This disconnection might be the advantages and characteristics of Chinese medicine differed from Western medicine treatment and provide a new basis for key scientific issues of the traditional Chinese medicine "different diseases". Moreover, through the implementation of this project, the platform associated with the overall evaluation of stroke in vivo would be established based on the dynamic association of central and peripheral inflammation related systems，which could be taken as a novel mode suitable for the research of the complex system of traditional Chinese medicine. And with the application of this new integration model and research mode, more adequate experimental evidences for the new treatment of "tonifying Qi combined with detoxifying toxic" would be provided to reveals its characteristics of Prescription and Compatibility Law.

本课题将前有基础，抗脑缺血药效显著，协同作用好的新的益气解毒中药复方作为研究对象，针对该方中出现的三个主要组成成分脂溶性差，不易透过血脑屏障，药物吸收差，口服生物利用度低的这种明显的药代动力学与药效不关联的中药用药普遍现象，拟从中枢和外周系统炎症网络整体调节的角度，阐释其科学本质，并提出这种不关联可能是中药不同于西药药效作用的优势体现的假说,并通过本课题的实验验证，为中药"异病同治"关键科学问题提供新依据，同时，通过本课题的实施，拟建立一个体现"中枢-外周炎症系统动态关联"的脑中风整体研究和评价平台，结合数据挖掘，多目标优化和系统建模技术，探索一种适合中药复杂体系研究的新模式，并拟采用新的整合模型和研究模式，为益气、解毒治法提供更充分的实验依据，揭示其组方特点和配伍规律。

中医重视整体观和辨证论治，中风病中医临床治疗仍以复方制剂为主，然而，中药复方中如何在机体内发挥整合药效，一直是中药复方研究亟待解决的关键瓶颈问题。缺血性脑中风可被认为是一种复杂的炎性疾病，脑缺血会引起中枢脑组织和外周免疫器官如脾脏以及外周血白细胞构成的炎症网络的整体失衡。本课题将前有基础，抗脑缺血药效显著的益气解毒方作为研究对象，针对该方中出现的“药代动力学与药效不关联”的中药用药普遍现象，从中枢和外周系统炎症网络整体调节的角度，阐释了其科学本质。本研究应用基因芯片和生物信息学分析构建中枢-外周炎性关联网络，发现了调控脑缺血病理过程的关键节点基因，探讨了益气解毒方对脑、脾、外周血白细胞中的炎性基因相关的通路和生物功能的整合调控作用，进而对炎症网络关键基因和益气解毒方干预的炎性细胞因子进行PCR和ELISA验证。本研究的科学意义在于1、首次从基因水平成功构建了脑中风的中枢-外周炎症网络，并基于该网络初步探讨了益气解毒方通过炎症网络调控的整合分子作用机制。2.基因芯片检测结果显示，在大鼠脑、脾、白细胞构成的中枢和外周相互作用炎症网络中，益气解毒方可多靶点平衡调控炎性基因，干预炎症反应过程，进而达到抗脑缺血损伤的作用，为其缺血性脑中风治疗作用提供了新的证据，同时也证明中药确实可通过作用于外周干预中枢从而发挥治疗作用。3.对选择的关键炎症基因和经典细胞因子进行验证，细胞因子结果进一步表明益气解毒方可通过中枢-外周炎症网络，直接干预脑缺血后炎症反应的发生。4.通过该项目的实施，建立了一个体现“中枢-外周炎症系统动态关联”的脑中风整体研究和评价平台，结合数据挖掘，探索了一种适合中药复杂体系研究的新模式，为益气、解毒治法提供更充分的实验依据，揭示其组方特点和配伍规律。