清热解毒是中医治疗热毒证清法的核心，药对是方剂组成的基本单元，也是揭示中药配伍七情合和理论的重要切入点。本课题以中医理论为指导，提出黄芩/栀子分别调控膜信号呈递和PI3K/AKT等通路上下游相互配合；金银花/连翘基于MAPK、JAK-STAT和PPAR通路网络调控，“相须为用，不可离分”的学术假说。围绕该假说建立以多种免疫调控因子为基础的UPLC-Q/TOF谱效筛选模型筛选药效分子；开展其治疗细菌性肺炎的系统生物学研究分析关键通路；引入化学生物学手段制备药效分子探针，开展靶点捕获以及细胞定位研究。建立一套“方剂组学-系统生物学-网络药理学-化学生物学”还原论的研究模式。通过整合药理学方法构建关键药效成分的免疫调控网络，在整体、细胞和分子水平诠释其免疫调节的生物学表达形式，从多维的角度验证黄芩/栀子、金银花/连翘的配伍机制，为清热解毒的机制研究提供创新性的技术方法。

Heat-clearing and detoxifying therapy is the core of heat toxin syndrome treatment induced by traditional Chinese medicine (TCM). The pair combination of Chinese herb medicines is the basic unit for TCM prescription, and reveals an important entry for TCM compatibility research. In TCM theory, integrating chemomics and network pharmacology information, we propose a hypothesis which covered the numerous immune regulation processes involved in signal presenting of cell membrane, PI3K/AKT, MAPK, JAK-STAT, and PPAR pathways induced by two synergistic combination, Scutellaria baicalensis/Gardenia jasminoides and Lonicera japonica/ Forsythia suspense, respectively. The project will focus on the establishment of UPLC-Q/TOF based, Cox, NO, NF-κB, IL, TNF-α and other immune regulatory factors’ bioactive-guided screening system to find critical ingredients, carry out the systems biology study to evaluate the mechanism of bacterial pneumonia treatment, introduce chemical biological technique to synthesis molecular probes of active ingredients, and carry out cellular localization and target capture chemical proteinomics research. Therefore, we advocated the contribution of a linkage system including "Fangjiomics-Systems Biology-Network pharmacology-Chemical Biology" to support the reductionism research model for TCM. Through the platform created by the integration of immune regulation network of the key ingredients, we try to reveal the biological function of synergistic action at overall, cell and molecular different levels. Furthermore, we hope the research approach which presented in this project will accelerate the understanding of the core mechanisms about heat-clearing and detoxifying of TCM prescriptions.