基于中药整合药理学计算平台的小柴胡汤抗脓毒症的分子机制研究
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摘要
目的:探讨小柴胡汤抗脓毒症的物质基础和作用机制,为该方的临床应用和研发提供参考。方法:借助中药整合药理学计算平台(TCMIP)进行小柴胡汤化学成分分析、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,对小柴胡汤抗脓毒症的作用机制进行探讨。结果:预测小柴胡汤的224个化学成分(包括柴胡皂苷、人参皂苷、甘草苷等)与脓毒症相关的118个核心靶标之间有相互作用,包括直接靶标血小板因子(PF)4、髓样分化因子(MYD)88、Toll样家族受体(TLR)4、CD14、一氧化氮合酶(NOS)3等,其抗脓毒症作用机制涉及神经系统、内分泌、免疫应答、能量代谢等。结论:小柴胡汤基于"神经-内分泌-免疫-代谢"等从多层面、多途径、多通路实现其抗脓毒症的作用。本研究初步揭示了小柴胡汤抗脓毒症潜在作用机制,为该方进一步的药效物质基础和作用机制研究以及临床应用提供了理论依据。
OBJECTIVE:To investigate the substance basis and mechanism of Xiaochaihu decoction in treatment of sepsis,and to provide reference for clinical application and R&D of the decoction. METHODS:Based on TCM integrative pharmacology platform(TCMIP),chemical component analysis of Xiaochaihu decoction,disease target prediction,gene function and pathway enrichment analysis were all performed. The multi-dimensional network relationship of"TCM-chemical components-core targets-key pathways"was established,and the mechanism of Xiaochaihu decoction in treatment of sepsis was investigated. RESULTS:A total of 224 predicted chemical ingredients of Xiaochaihu decoction(including saikoside,ginsenoside,glycyrrhizin,etc.) interacted with 118 key targets about sepsis,including PF4,MYD88,TLR4,CD14,NOS3,etc. Its anti-sepsis mechanism involved nervoussystem, endocrine system, immune response and energy metabolism, etc. CONCLUSIONS: Based on "neuronalendocrine-immune-metabolism",Xiaochaihu decoction achieved its role in regulating sepsis by multi-level,multi-channel and multi-channel. This research may reveal the potential mechanism of Xiaochaihu decoction for sepsis,and the prescription provide theoretical basis for further experimental research of pharmacodynamic substance basis and mechanism of action.
OBJECTIVE:To investigate the substance basis and mechanism of Xiaochaihu decoction in treatment of sepsis,and to provide reference for clinical application and R&D of the decoction. METHODS:Based on TCM integrative pharmacology platform(TCMIP),chemical component analysis of Xiaochaihu decoction,disease target prediction,gene function and pathway enrichment analysis were all performed. The multi-dimensional network relationship of"TCM-chemical components-core targets-key pathways"was established,and the mechanism of Xiaochaihu decoction in treatment of sepsis was investigated. RESULTS:A total of 224 predicted chemical ingredients of Xiaochaihu decoction(including saikoside,ginsenoside,glycyrrhizin,etc.) interacted with 118 key targets about sepsis,including PF4,MYD88,TLR4,CD14,NOS3,etc. Its anti-sepsis mechanism involved nervoussystem, endocrine system, immune response and energy metabolism, etc. CONCLUSIONS: Based on "neuronalendocrine-immune-metabolism",Xiaochaihu decoction achieved its role in regulating sepsis by multi-level,multi-channel and multi-channel. This research may reveal the potential mechanism of Xiaochaihu decoction for sepsis,and the prescription provide theoretical basis for further experimental research of pharmacodynamic substance basis and mechanism of action.
引文
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[16]王丽敏,张丽艳,谷松.解析小柴胡汤“和法”调节自身免疫性疾病机制[J].中华中医药学刊,2018,36(1):218-220.
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[22]袁晓雯,姜楠,陈冰.单味中药治疗脓毒症的研究进展[J].中国中医基础医学杂志,2017,23(5):736-739.
[23]吴晓民,赵丹,朱艳萍.人参多糖的药理作用与临床研究进展[J].人参研究,2016,28(5):40-46.
[24]吴宗耀,牛李义,梁喜爱.甘草化学成分及药理作用分析[J].河南中医,2010,30(12):1235-1236.
[25]丁岗强,康谊,刘俊平.甘草甜素对脓毒症小鼠急性肺损伤保护作用的实验研究[J].中华医院感染学杂志,2014,23(19):4742-4744.
[26]李发胜,赵珏,池晓峰.甘草多糖对小鼠免疫调节作用的影响[J].中国中医药信息杂志,2009,16(6):35-36.
[27]吴国泰,何小飞,牛亭惠.大枣的化学成分、药理及应用[J].中国果菜,2016,36(10):25-28.
[28]高群.生姜醇提物抗肿瘤作用的实验研究[J].科技信息,2010,7(16):784-788.
[29]靳晓琪,黄传奇,张耕.半夏原植物性状、功效、禁忌、毒性以及炮制工艺考证[J].中国药房,2018,29(23):3289-3292.
[30]师灵灵,韩艳秋,任慧娟.脓毒症的病理生理机制研究进展[J].中华医院感染学杂志,2016,26(8):1914-1916.
[31]赵战芝,何钒,唐雅玲.PF4通过NF-κB上调巨噬细胞MMP-9表达[J].中南医学科学杂志,2015,43(1):9-13.
[32]林幼萍,冯茹.脓毒症患者血小板参数检测的临床意义[J].内科急危重症杂志,2013,19(3):163-164.
[33]张建平,苏云,张立宏.脓毒症患者TLR-4、TIRAP/Mal基因多态性的探讨[J].临床医药文献电子杂志,2018,5(42):36-42.
[34]李炯,叶圳,顾宏刚.锦红汤对脓毒症大鼠小肠TLR4及其信号通路表达的影响[J].河南中医,2018,38(5):690-693.
[35]李淑芳,汪海慧,闫国良.抗炎合剂对脓毒症急性肺损伤TLR4/MyD88信号通路的干预研究[J].上海中医药杂志,2017,51(1):177-180.
[36]傅聪.缓激肽B2受体信号通路抑制氧化应激诱导的内皮祖细胞和心脏干细胞衰老的机制研究[D].南京:东南大学,2016.
[37]杨蕊,许华,王兵.PI3K/AKT信号通路在大鼠腹腔感染性脓毒症急性肾损伤中的作用[J].天津医药,2018,46(6):581-584.
[38]刘艺欣,贾宝辉,黄兆豪,等.脓毒症中的先天免疫、能量改变与自噬[J].南昌大学学报(医学版),2018,58(2):92-96.
[39]翟建华,么颖,刘晨燕.脓毒症患者内分泌代谢变化[J].继续医学教育,2018,3(1):98-100.
[40]王缨,朱建军,曾晓辉.小柴胡汤免疫-内分泌调节药理研究概述[J].辽宁中医杂志,2008,35(12):1949-1950.
[2]闫圣涛,李红伟,张国虹,等.脓毒症发病机制及标志物新进展[J].中日友好医院学报,2014,28(6):355-357.
[3]姚咏明,张卉,李春盛.脓毒症治疗新策略:免疫调理研究新认识[J].医学与哲学,2017,38(2):28-31.
[4]金方明,方泰惠,周玲玲.小柴胡汤的免疫药理学研究进展[J].陕西中医,2004,25(1):92-93.
[5]吴贵娥.小柴胡汤古代运用考探[D].北京:北京中医药大学,2005.
[6]曹秋梅,许周洁,聂源,等.浅析小柴胡汤近十年药理研究与临床应用[J].亚太传统医药,2017,13(2):76-77.
[7]许海玉,杨洪军.整合药理学:中药现代研究新模式[J].中国中药杂志,2014,39(3):357-362.
[8]薛潇春,胡晋红.网络药理学的研究方法与应用进展[J].药学实践杂志,2015,33(5):401-405.
[9]许海玉,刘振明,付岩.中药整合药理学计算平台的开发与应用[J].中国中药杂志,2017,42(18):3633-3638.
[10]ZHANG Y,MAO X,SU J.A network pharmacologybased strategy deciphers the underlying molecular mechanisms of Qixuehe capsule in the treatment of menstrual disorders[J].Chin Med,2017,12(1):23-39.
[11]YU G,ZHANG Y,REN W.Network pharmacology-based identification of key pharmacological pathways of YinHuang-Qing-Fei capsule acting on chronic bronchitis[J].Int J Chronic Obstr,2017,12(2):85-94.
[12]BHOLA PD,LETAI A.Mitochondria-judges and executioners of cell death sentences[J].Molecular Cell,2016,61(5):695-704.
[13]赵裕沛,王兴华.小柴胡汤临床应用近况[J].甘肃中医,2006,19(12):42-44.
[14]张玲玲,史欣德.小柴胡汤治疗发热的调查分析[J].辽宁中医学院学报,2003,5(4):311-313.
[15]钱妍,吴整军.小柴胡汤抗感染与解热作用的实验研究[J].中华医院感染学杂志,2008,18(4):576-578.
[16]王丽敏,张丽艳,谷松.解析小柴胡汤“和法”调节自身免疫性疾病机制[J].中华中医药学刊,2018,36(1):218-220.
[17]卢幼然,狄浩然,丁军颖.脓毒症免疫失衡机制及中医治疗[J].世界中医药,2018,13(9):2362-2366.
[18]颜美玲,杨柳,侯阿娇.柴胡化学成分及药理作用研究进展[J].中医药信息,2018,10(5):103-109.
[19]袁晓雯,姜楠,陈冰.单味中药治疗脓毒症的研究进展[J].中国中医基础医学杂志,2017,23(5):736-739.
[20]吉晓丽.黄芩的化学成分与药理作用研究进展[J].中医临床研究,2017,9(9):128-129.
[21]雷玲,胡竟一,余悦.黄芩的抗内毒素作用研究[J].中药药理与临床,2007,23(3):46-47.
[22]袁晓雯,姜楠,陈冰.单味中药治疗脓毒症的研究进展[J].中国中医基础医学杂志,2017,23(5):736-739.
[23]吴晓民,赵丹,朱艳萍.人参多糖的药理作用与临床研究进展[J].人参研究,2016,28(5):40-46.
[24]吴宗耀,牛李义,梁喜爱.甘草化学成分及药理作用分析[J].河南中医,2010,30(12):1235-1236.
[25]丁岗强,康谊,刘俊平.甘草甜素对脓毒症小鼠急性肺损伤保护作用的实验研究[J].中华医院感染学杂志,2014,23(19):4742-4744.
[26]李发胜,赵珏,池晓峰.甘草多糖对小鼠免疫调节作用的影响[J].中国中医药信息杂志,2009,16(6):35-36.
[27]吴国泰,何小飞,牛亭惠.大枣的化学成分、药理及应用[J].中国果菜,2016,36(10):25-28.
[28]高群.生姜醇提物抗肿瘤作用的实验研究[J].科技信息,2010,7(16):784-788.
[29]靳晓琪,黄传奇,张耕.半夏原植物性状、功效、禁忌、毒性以及炮制工艺考证[J].中国药房,2018,29(23):3289-3292.
[30]师灵灵,韩艳秋,任慧娟.脓毒症的病理生理机制研究进展[J].中华医院感染学杂志,2016,26(8):1914-1916.
[31]赵战芝,何钒,唐雅玲.PF4通过NF-κB上调巨噬细胞MMP-9表达[J].中南医学科学杂志,2015,43(1):9-13.
[32]林幼萍,冯茹.脓毒症患者血小板参数检测的临床意义[J].内科急危重症杂志,2013,19(3):163-164.
[33]张建平,苏云,张立宏.脓毒症患者TLR-4、TIRAP/Mal基因多态性的探讨[J].临床医药文献电子杂志,2018,5(42):36-42.
[34]李炯,叶圳,顾宏刚.锦红汤对脓毒症大鼠小肠TLR4及其信号通路表达的影响[J].河南中医,2018,38(5):690-693.
[35]李淑芳,汪海慧,闫国良.抗炎合剂对脓毒症急性肺损伤TLR4/MyD88信号通路的干预研究[J].上海中医药杂志,2017,51(1):177-180.
[36]傅聪.缓激肽B2受体信号通路抑制氧化应激诱导的内皮祖细胞和心脏干细胞衰老的机制研究[D].南京:东南大学,2016.
[37]杨蕊,许华,王兵.PI3K/AKT信号通路在大鼠腹腔感染性脓毒症急性肾损伤中的作用[J].天津医药,2018,46(6):581-584.
[38]刘艺欣,贾宝辉,黄兆豪,等.脓毒症中的先天免疫、能量改变与自噬[J].南昌大学学报(医学版),2018,58(2):92-96.
[39]翟建华,么颖,刘晨燕.脓毒症患者内分泌代谢变化[J].继续医学教育,2018,3(1):98-100.
[40]王缨,朱建军,曾晓辉.小柴胡汤免疫-内分泌调节药理研究概述[J].辽宁中医杂志,2008,35(12):1949-1950.