基于网络药理学探究苓桂术甘汤治疗慢性心力衰竭的作用机制
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摘要
目的:探讨苓桂术甘汤功效物质基础及对慢性心力衰竭的作用机制。方法:根据药物ADME特性,借助TCMSP平台遴选苓桂术甘汤中的活性成分和作用靶点,构建成分-靶点网络;基于TTD、Genecards数据库遴选慢性心力衰竭相关的靶点,结合String数据库构建成分靶点-疾病靶点蛋白互作全局网络,并通过生物信息学手段对重叠靶点进行GO注释及通路分析。结果:本研究共获得50个活性成分,对应76个靶点,包括与慢性心力衰竭相关的20个重叠靶点;共富集出38个GO注释条目,经Bonferroni校正P值均<0.01,经Kappa算法分为类固醇激素受体激活、调节心率、调控血压、负调节血压4大类别;获得13条信号通路,经Bonferroni校正P值均<0.05,经Kappa算法分为单胺类G蛋白偶联受体、一氧化氮的调节作用、核受体、叶酸代谢4大类别。结论:本研究结果初步预测了苓桂术甘汤对慢性心力衰竭的基本药理基础及功效机制,与现代临床用药规律契合,为下一步深入验证奠定了良好理论基础。
Objective:To investigate the efficacy and compatibility mechanism of Ling-Gui-Zhu-Gan decoction treatment in Chronic Heart Failure(CHF).Method:We selected active ingredients accoding to drugs' ADME parameters and found the related targets by searching in TCMSP.Meanwhile we built the component-target network and selected chronic heart failure related genes from TTD and Genecards Databases.We constructe component target-disease target protein-protein interaction network searched in String Database and used bioinformatics method to annotate the 20 overlap targets and analyze their enrichment results of GO and pathway.Result:The 50 active ingredients,76 corresponding target,including 20 CHF related targets were screened out.A total of 38GO-terms were enriched,all P value<0.01(Bonferroni-adjusted).According to kappa algorithm,a total of 4groups enriched:steroid hormone receptor activity,regulation of heart rate,regulation of blood pressure,negative regulation of blood pressure.A total of 13pathway-terms were enriched,all P value<0.05(Bonferroni-adjusted).According to kappa algorithm,a total of 4groups enriched:Monoamine GPCRs,Effects of Nitric Oxide,Nuclear Receptors,Folate Metabolism.Conclusion:The result of the study preliminarily verifies the basic pharmacological effects of Ling-Gui-Zhu-Gan decoction and its chronic heart failure related mechanisms.
Objective:To investigate the efficacy and compatibility mechanism of Ling-Gui-Zhu-Gan decoction treatment in Chronic Heart Failure(CHF).Method:We selected active ingredients accoding to drugs' ADME parameters and found the related targets by searching in TCMSP.Meanwhile we built the component-target network and selected chronic heart failure related genes from TTD and Genecards Databases.We constructe component target-disease target protein-protein interaction network searched in String Database and used bioinformatics method to annotate the 20 overlap targets and analyze their enrichment results of GO and pathway.Result:The 50 active ingredients,76 corresponding target,including 20 CHF related targets were screened out.A total of 38GO-terms were enriched,all P value<0.01(Bonferroni-adjusted).According to kappa algorithm,a total of 4groups enriched:steroid hormone receptor activity,regulation of heart rate,regulation of blood pressure,negative regulation of blood pressure.A total of 13pathway-terms were enriched,all P value<0.05(Bonferroni-adjusted).According to kappa algorithm,a total of 4groups enriched:Monoamine GPCRs,Effects of Nitric Oxide,Nuclear Receptors,Folate Metabolism.Conclusion:The result of the study preliminarily verifies the basic pharmacological effects of Ling-Gui-Zhu-Gan decoction and its chronic heart failure related mechanisms.
引文
[1]万宇,李南夷,郝蔷薇.经方治疗慢性心衰概况[J].实用中医内科杂志,2016,30(2):114-117.
[2]施慧,许闪,王靓,等.苓桂术甘汤调节心室重构模型大鼠心肌组织NF-κB信号通路的分子机制研究[J].中药材,2017,40(3):680-683.
[3]康天济,韩宇博,田苗,等.苓桂术甘汤对心肌缺血再灌注损伤SOD,MDA含量的影响[J].中医药信息,2014(3):53-55.
[4]刘志华,孙晓波.网络药理学:中医药现代化的新机遇[J].药学学报,2012,10(6):696-703.
[5] Harel A,Inger A,Stelzer G,et al.GIFtS:annotation landscape analysis with GeneCards[J].BMC bioinformatics,2009,10(1):348-348.
[6] Stelzer G,Rosen N,Plaschkes I,et al.The genecards suite:from gene data mining to disease genome sequence analyses[J].Curr Protoc Bioinformatics,2016,54:130-133.
[7] Safari-Alighiarloo N,Taghizadeh M,Rezaei-Tavirani M,et al.Protein-protein interaction networks(PPI)and complex diseases[J].Gastroenterol Hepatol Bed Bench,2014,7(1):17-19.
[8] Saeidnia S,Manayi A,Gohari AR,et al.The Story of Beta-sitosterol-A[J].Review,2014,32(2):230-233.
[9] Olaiya CO,Omolekan TO,Esan AM,et al.Renal,Cardiac and Osteo-protective effects of beta-sitosterol glycoside in hypertensive rats[J].Adv Life Sci Technol,2015,39(1):13-18.
[10]Clifton-Bligh P B,Nery ML,Clifton-Bligh RJ,et al.Red clover isoflavones enriched with formononetin lower serum LDL cholesterol-a randomized,doubleblind,placebo-controlled study[J].Euro J Clin Nutri,2015,69(1):134-142.
[11]Cheng Y,Xia Z,Han Y,et al.Plant natural product formononetin protects rat cardiomyocyte H9c2cells against oxygen glucose deprivation and reoxygenation via inhibiting ROS formation and promoting GSK-3βphosphorylation[J].Oxid Med Cell Longev,2016,2016:2060874.
[12]Dong Z,Shi Y,Zhao H,et al.Sulphonated formononetin induces angiogenesis through vascular endothelial growth factor/cAMP response element-binding protein/early growth response 3/vascular cell adhesion molecule 1and wnt/β-catenin signaling pathway[J].Pharmacology,2018,101(1-2):76-85.
[13]Xing Y,Hu D,Zhang T,et al.Traditional Chinese medicine and vascular disease[J].Evid Based Complement Alternat Med,2015,2015:430818.
[14]朱科,张军平,李萌.神经型一氧化氮合酶在冠心病中的研究进展[J].临床心血管病杂志,2017,33(3):207-210.
[15]吴纪珍,齐咏,郭亚丽,等.内皮型一氧化氮合酶基因多态性与静脉血栓栓塞症相关性的荟萃分析[J].临床心血管病杂志,2018,34(5):83-86.
[16]Tang L,Wang H,Ziolo MT.Targeting NOS as a therapeutic approach for heart failure[J].Pharmacology&Therapeutics,2014,142(3):306-315.
[17]Fukami K,Yamagishi S,Okuda S.Role of AGEsRAGE system in cardiovascular disease[J].Curr Pharmac Des,2014,20(14):2395-2402.
[18]Yancy CW,Jessup M,Bozkurt B,et al.2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure[J].J Cardiac Fail,2016,22(9):659-669.
[19]Ju C,Ye M,Li F.Plasma brain natriuretic peptide,endothelin-1,and matrix metalloproteinase 9expression and significance in type 2diabetes mellitus patients with ischemic heart disease[J].Med Sci Monit,2015,21(10):2094-2096.
[20]De Zeeuw D,Coll B,Andress D,et al.The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2diabetic nephropathy[J].J Am Soc Nephrol,2014,25(5):1083-1093.
[21]陈海荣,潘碧云,李名兰,等.高血压患者血浆肾素-血管紧张素-醛固酮系统活性水平与降压效果的关系[J].临床心血管病杂志,2017,33(9):875-879.
[2]施慧,许闪,王靓,等.苓桂术甘汤调节心室重构模型大鼠心肌组织NF-κB信号通路的分子机制研究[J].中药材,2017,40(3):680-683.
[3]康天济,韩宇博,田苗,等.苓桂术甘汤对心肌缺血再灌注损伤SOD,MDA含量的影响[J].中医药信息,2014(3):53-55.
[4]刘志华,孙晓波.网络药理学:中医药现代化的新机遇[J].药学学报,2012,10(6):696-703.
[5] Harel A,Inger A,Stelzer G,et al.GIFtS:annotation landscape analysis with GeneCards[J].BMC bioinformatics,2009,10(1):348-348.
[6] Stelzer G,Rosen N,Plaschkes I,et al.The genecards suite:from gene data mining to disease genome sequence analyses[J].Curr Protoc Bioinformatics,2016,54:130-133.
[7] Safari-Alighiarloo N,Taghizadeh M,Rezaei-Tavirani M,et al.Protein-protein interaction networks(PPI)and complex diseases[J].Gastroenterol Hepatol Bed Bench,2014,7(1):17-19.
[8] Saeidnia S,Manayi A,Gohari AR,et al.The Story of Beta-sitosterol-A[J].Review,2014,32(2):230-233.
[9] Olaiya CO,Omolekan TO,Esan AM,et al.Renal,Cardiac and Osteo-protective effects of beta-sitosterol glycoside in hypertensive rats[J].Adv Life Sci Technol,2015,39(1):13-18.
[10]Clifton-Bligh P B,Nery ML,Clifton-Bligh RJ,et al.Red clover isoflavones enriched with formononetin lower serum LDL cholesterol-a randomized,doubleblind,placebo-controlled study[J].Euro J Clin Nutri,2015,69(1):134-142.
[11]Cheng Y,Xia Z,Han Y,et al.Plant natural product formononetin protects rat cardiomyocyte H9c2cells against oxygen glucose deprivation and reoxygenation via inhibiting ROS formation and promoting GSK-3βphosphorylation[J].Oxid Med Cell Longev,2016,2016:2060874.
[12]Dong Z,Shi Y,Zhao H,et al.Sulphonated formononetin induces angiogenesis through vascular endothelial growth factor/cAMP response element-binding protein/early growth response 3/vascular cell adhesion molecule 1and wnt/β-catenin signaling pathway[J].Pharmacology,2018,101(1-2):76-85.
[13]Xing Y,Hu D,Zhang T,et al.Traditional Chinese medicine and vascular disease[J].Evid Based Complement Alternat Med,2015,2015:430818.
[14]朱科,张军平,李萌.神经型一氧化氮合酶在冠心病中的研究进展[J].临床心血管病杂志,2017,33(3):207-210.
[15]吴纪珍,齐咏,郭亚丽,等.内皮型一氧化氮合酶基因多态性与静脉血栓栓塞症相关性的荟萃分析[J].临床心血管病杂志,2018,34(5):83-86.
[16]Tang L,Wang H,Ziolo MT.Targeting NOS as a therapeutic approach for heart failure[J].Pharmacology&Therapeutics,2014,142(3):306-315.
[17]Fukami K,Yamagishi S,Okuda S.Role of AGEsRAGE system in cardiovascular disease[J].Curr Pharmac Des,2014,20(14):2395-2402.
[18]Yancy CW,Jessup M,Bozkurt B,et al.2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure[J].J Cardiac Fail,2016,22(9):659-669.
[19]Ju C,Ye M,Li F.Plasma brain natriuretic peptide,endothelin-1,and matrix metalloproteinase 9expression and significance in type 2diabetes mellitus patients with ischemic heart disease[J].Med Sci Monit,2015,21(10):2094-2096.
[20]De Zeeuw D,Coll B,Andress D,et al.The endothelin antagonist atrasentan lowers residual albuminuria in patients with type 2diabetic nephropathy[J].J Am Soc Nephrol,2014,25(5):1083-1093.
[21]陈海荣,潘碧云,李名兰,等.高血压患者血浆肾素-血管紧张素-醛固酮系统活性水平与降压效果的关系[J].临床心血管病杂志,2017,33(9):875-879.