中国中药杂志

2019, v.44(13) 2691-2700

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基于整合药理学平台的桂枝-白芍药对抗脓毒症的分子机制研究
Molecular mechanism of Cinnamomi Ramulus-Paeoniae Radix Alba drug pair against sepsis based on integrative pharmacology platform of traditional Chinese medicine

杨清鑫;吕红君;王小博;姜蕾;曾南;
YANG Qing-xin;LYU Hong-jun;WANG Xiao-bo;JIANG Lei;ZENG Nan;the Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine,Key Laboratory of Systematic Research,Development and Utilization of Chinese Medicine Resources in Sichuan Province-Key Laboratory Breeding Base of Co-founded by Sichuan Province and MOST,Pharmacy College,Chengdu University of Traditional Chinese Medicine;Department of Neurology,Kaifeng Central Hospital;

摘要(Abstract):

桂枝汤属于解表剂,为中医经典复方,临床上治疗脓毒症的疗效确切。但由于经方的复杂性,其抗脓毒症的机制难以明确,"桂枝-白芍"药对为调和营卫经典配伍,是桂枝汤的核心,该研究以桂枝-白芍为研究对象,借助整合药理学平台(TCMIP,http://www.tcmip.cn/),进行桂枝-白芍化学成分分析、疾病靶标预测、基因功能和通路富集分析,并建立"中药-化学成分-核心靶标-关键通路"的多维网络关系,对桂枝-白芍治疗脓毒症的作用机制进行探讨。"桂枝-白芍"药对预测结果表明桂枝-白芍药对抗脓毒症主要与45个化学成分相关,其活性成分可针对多个靶点、多条通路发挥抗脓毒症的作用,其作用涉及PF4,MyD88,TLR4,BDKRB2,CD14,NOS3等炎症靶标,主要通过Toll样受体信号通路、叉头转录因子Fox O信号通路、趋化因子信号通路等炎症通路、甲状腺素、胰岛素信号通路等代谢通路、催产素信号通路、雌激素信号通路等与内分泌系统相关通路来调节脓毒症。该研究为进一步开发桂枝-白芍药对及桂枝汤抗脓毒症的作用机制提供了科学依据。
Guizhi Decoction is a resolving agent,which is a classic prescription for traditional Chinese medicine. It is effective in the treatment of sepsis in clinical practice. However,due to the complexity of the prescription,its anti-sepsis mechanism is difficult to be clarified. The " Cinnamomi Ramulus-Paeoniae Radix Alba" drug pair,as the classic compatibility for medicinal and medicinal herbs,is the core of Guizhi Decoction. In this study,Cinnamomi Ramulus-Paeoniae Radix Alba drug pair was used as the research object and the molecular mechanism of its treatment of sepsis was investigated by analyzing the chemical compositions with integrative pharmacology platform( TCMIP,http://www.tcmip.cn/),predicting disease target,analyzing gene function and pathway of " Cinnamomi Ramulus-Paeoniae Radix Alba" in treatment of sepsis,and establishing a multi-dimensional network relationship of " Chinese medicine-chemical components-core targets-key pathways". The prediction results of " Cinnamomi Ramulus-Paeoniae Radix Alba" drug pair showed that its anti-sepsis effect was associated with 45 active components,and the active components played an anti-sepsis role through multiple targets and pathways,involving inflammatory targets such as PF4,MyD88,TLR4,BDKRB2,CD14,and NOS3. The sepsis was relieved mainly by regulating Toll like signaling pathway,Fox O signaling pathway,chemokines signaling pathway,thyroid and insulin endocrine signaling pathways and biological processes. This study provides a scientific basis for further development of Cinnamomi Ramulus-Paeoniae Radix Alba drug pair and Guizhi Decoction against sepsis.

关键词(KeyWords): 桂枝-白芍;药对;整合药理学;脓毒症;作用机制;靶点;通路分析;相互作用网络
Cinnamomi Ramulus-Paeoniae Radix Alba;drug pair;integrative pharmacology;sepsis;mechanism of action;target;pathway analysis;interaction network

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81473399);; 成都市科技局科技惠民项目(2015-HM01-00187-SF)

作者(Authors): 杨清鑫;吕红君;王小博;姜蕾;曾南;
YANG Qing-xin;LYU Hong-jun;WANG Xiao-bo;JIANG Lei;ZENG Nan;the Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine,Key Laboratory of Systematic Research,Development and Utilization of Chinese Medicine Resources in Sichuan Province-Key Laboratory Breeding Base of Co-founded by Sichuan Province and MOST,Pharmacy College,Chengdu University of Traditional Chinese Medicine;Department of Neurology,Kaifeng Central Hospital;

DOI: 10.19540/j.cnki.cjcmm.20190416.404

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