中文摘要
血府逐瘀汤从瘀论治创伤性颅脑损伤(TBI)获得了多项临床证据支持,但其多靶点作用机制有待阐明。我们前期已证实:血府逐瘀汤抑制TBI大鼠脑区PI3K/Akt/mTOR信号通路,下调花生四烯酸(AA)及其介导的TNF-α和IL-1β水平。以此为线索,我们最近基于代谢组学结合生物信息学研究,捕获到血府逐瘀汤治疗TBI涉及AA代谢-炎症的靶标证据。据此提出假说:血府逐瘀汤通过调控AA代谢-炎症网络治疗TBI。为验证该假说,本项目拟以中医整体观和系统生物学为指导,应用定量蛋白质组学-代谢组学方法明确血府逐瘀汤调控AA代谢-炎症反应治疗TBI大鼠的分子靶标群;利用生物信息学手段构建上述多靶点、多信号通路参与的网络图谱;结合体内外实验,采用分子生物学方法最终证实这一网络;以揭示血府逐瘀汤靶向AA代谢-炎症反应治疗TBI的网络调控机制。本项目将为解析血府逐瘀汤从瘀论治TBI的网络效应及科学内涵提供新视角。
英文摘要
Based on the idea from Chinese theory “Cong Yu Lun Zhi”, TBI treatment with Xuefu Zhuyu decoction (XFZY) was supported by much clinical evidence, but the corresponding mechanisms of its multi-target action remains to be elucidated. Our previous animal experiments confirmed that XFZY down-regulated the levels of arachidonic acid (AA), TNF-α and IL-1β via inhibiting PI3K/Akt/mTOR signal pathway in the brain regions following TBI. Based on this clue, our recent experiments of metabolomics combined with bioinformatics analysis showed that TBI treatment with XFZY referred to the regulation of AA metabolism-inflammatory cascade reaction. Hence, we proposed a hypothesis that XFZY performed TBI treatment through target regulation of AA metabolism-inflammatory reaction. To confirm this scientific hypothesis, under the guidance of TCM holism and systemic biology, this project aims to use quantitative proteomics-metabolomics techniques to capture the key molecular clusters referred to AA metabolism-inflammatory reaction after XFZY treatment following TBI in a rat model; to apply bioinformatics analysis methods to build the network map of regulating AA metabolism-inflammation, and finally to utilize molecular biological methods to verify the above network map according to in vivo and in vitro studies. This plan will provide the new perspective for the effects of network regulation and modern scientific understanding after XFZY treatment following TBI based on the Chinese theory “Cong Yu Lun Zhi”.
