基于网络药理学方法研究补肾活血方治疗肾纤维化药效物质基础及分子作用机制
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摘要
目的:探讨补肾活血方治疗肾纤维化的药效物质基础及分子作用机制。方法:基于网络药理学理论框架,结合ADME性质筛选、靶点预测、网络构建及KEGG通路富集分析等方法进行研究。结果:补肾活血方中5味药材共包含491个化合物,其中具有良好的ADME性质的188个潜在活性成分中,共有136个活性成分及其对应的59个靶标与补肾活血方治疗肾纤维化密切相关。通过构建"药材-活性成分-靶标"网络及对网络进行分析,共获得19个关键化合物和5个关键靶标。此外,在对靶标进行KEGG通路分析时,共获得19条与补肾活血方治疗肾纤维化相关的通路,其中,PI3K-Akt信号通路、MAPK信号通路、HIF-1信号通路为主要通路。结论:补肾活血方可通过多成分、多靶标及多通路的作用模式治疗肾纤维化。本研究为补肾活血方治疗肾纤维化的药效物质及潜在作用机制研究提供了一种新的研究思路,为该方剂的进一步升级改造及临床研究提供了必要的理论依据。
Objective:Investigate the pharmacodynamic material basis and molecular mechanism of Bushen Huoxue prescription in treatment of renal fibrosis.Methods:Based on the theoretical framework of network pharmacology,ADME screening,target prediction,network construction and KEGG pathway enrichment analysis were applied for this work.Results:There were 491 compounds in the 5 medicinal herbs of Bushen Huoxue prescription.In these compounds,188 compounds were as potential active components with good ADME properties,and 136 active compounds and corresponding 59 targets were closely related to Bushen Huoxue prescription in the treatment of renal fibrosis.By constructing and analyzing the active ingredients-targets network,19 key compounds and 5 key targets were obtained.In addition,the KEGG pathway analysis showed that 19 pathways related to the Bushen Huoxue prescription for kidney fibrosis,and PI3 K-Akt pathway,MAPK signaling pathway and HIF-1 signaling pathway were the major pathways.Conclusion:Bushen Huoxue prescription can treat renal fibrosis through multi-component,multi-target and multi-pathway.This study provides a new idea for the study of the pharmacodynamic substances and potential mechanism of Bushen Huoxue prescription in the treatment of renal fibrosis,and provides the necessary theoretical basis for the further upgrading and clinical research of the prescription.
Objective:Investigate the pharmacodynamic material basis and molecular mechanism of Bushen Huoxue prescription in treatment of renal fibrosis.Methods:Based on the theoretical framework of network pharmacology,ADME screening,target prediction,network construction and KEGG pathway enrichment analysis were applied for this work.Results:There were 491 compounds in the 5 medicinal herbs of Bushen Huoxue prescription.In these compounds,188 compounds were as potential active components with good ADME properties,and 136 active compounds and corresponding 59 targets were closely related to Bushen Huoxue prescription in the treatment of renal fibrosis.By constructing and analyzing the active ingredients-targets network,19 key compounds and 5 key targets were obtained.In addition,the KEGG pathway analysis showed that 19 pathways related to the Bushen Huoxue prescription for kidney fibrosis,and PI3 K-Akt pathway,MAPK signaling pathway and HIF-1 signaling pathway were the major pathways.Conclusion:Bushen Huoxue prescription can treat renal fibrosis through multi-component,multi-target and multi-pathway.This study provides a new idea for the study of the pharmacodynamic substances and potential mechanism of Bushen Huoxue prescription in the treatment of renal fibrosis,and provides the necessary theoretical basis for the further upgrading and clinical research of the prescription.
引文
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[20]杨梦思,周娜,王志钢,等.转录因子HIF-1α及其信号通路在疾病发生中的作用研究进展[J].生物技术通报,2016,32(8):8-13.
[21]袁明霞,唐荣,周巧玲,等.冬虫夏草对糖尿病肾病大鼠肾组织HIF-1α及VEGF表达的影响[J].中南大学学报:医学版,2013,38(5):448-457.
[22]Cai X,Huang Y,Zhang X,et al.Cloning,characterization,hypoxia and heat shock response of hypoxia inducible factor-1(HIF-1)from the small abalone Haliotis diversicolor[J].Gene,2014,534(2):256.
[2]韩聪祥,于立新,谢庆祥,等.血管紧张素II1型受体和转化生长因子-β1在慢性移植肾肾病中的关系及意义[J].中国现代医学杂志,2005,15(10):1465-1468.
[3]段晓虹,董竞成,何立群,等.补肾活血方对慢性肾炎肾虚血瘀证患者蛋白尿、尿IL-6、TGF-β1及MCP-1的影响[J].中国中西医结合杂志,2011,31(6):765-768.
[4]郭家安,王红燕.益气养阴补肾活血方治疗早期糖尿病肾病的临床研究[J].中医学报,2013,28(9):1348-1349.
[5]Ru J,Li P,Wang J,et al.TCMSP:a database of systems pharmacology for drug discovery from herbal medicines[J].Journal of Cheminformatics,2014,6(1):13.
[6]张文娟,王永华.系统药理学原理、方法及在中医药中的应用[J].世界中医药,2015,10(2):280-286.
[7]Zhang JX,Yan L,Chen XT,et al.Systems pharmacology dissection of multi-scale mechanisms of action for herbal medicines in stroke treatment and prevention[J].PLoS ONE,2014,9(8):e102506.
[8]Yu H,Chen J,Xu X,et al.A systematic prediction of multiple drug-target interactions from chemical,genomic,and pharmacological data[J].Plos ONE,2012,7(5):e37608.
[9]申兵冰.槲皮素对系膜细胞增殖、凋亡作用及其对细胞外基质、MCP-1分泌影响的实验研究[D].四川大学,2006.
[10]张兆洲,戴恩来.槲皮素在慢性肾脏病防治中的研究进展[J].中国民族民间医药,2015,24(11):17-18.
[11]陈妮,韩鹏定,陈文,等.山奈酚对高糖诱导大鼠肾系膜细胞增殖的影响[J].四川大学学报:医学版,2017,48(4):526-530.
[12]Frungieri M B,Weidinger S,Meineke V,et al.Proliferative action of mast-cell tryptase is mediated by PAR2,COX2,prostaglandins,and PPARgamma:Possible relevance to human fibrotic disorders[J].Proceedings of the National Academy of Sciences of the United States of America,2002,99(23):15072-15077.
[13]牛永红,谢正祥,殷跃辉.β肾上腺素能受体基因多态性与原发性高血压的关系[J].中国组织工程研究,2007,11(12):2243-2246.
[14]马全中,郭志勇.高血压肾病的研究现状[J].中国医药导报,2012,9(33):32-33.
[15]吴弘,肖君华,蔡刚明,等.高血压病患者β2-肾上腺素能受体基因5′-调控区单核苷酸多态性研究[J].中华医学杂志,2001,81(1):23-26.
[16]迟毓婧,李晶,管又飞,等.PI3K-Akt信号传导通路对糖代谢的调控作用[J].中国生物化学与分子生物学报,2010,26(10):879-885.
[17]赵青,万毅刚,王朝俊,等.慢性肾脏病肾组织炎症信号通路p38MAPK的调节机制及中药的干预作用[J].中国中药杂志,2012,37(12):1700-1704.
[18]Wang J,Huang H,Liu P,et al.Inhibition of phosphorylation of p38 MAPK involved in the protection of nephropathy by emodin in diabetic rats[J].European Journal of Pharmacology,2006,553(1):297-303.
[19]陈好利,万毅刚,赵青,等.糖尿病肾病肾组织炎症信号通路p38MAPK的调节机制及中药的干预作用[J].中国中药杂志,2013,38(14):2268-2272.
[20]杨梦思,周娜,王志钢,等.转录因子HIF-1α及其信号通路在疾病发生中的作用研究进展[J].生物技术通报,2016,32(8):8-13.
[21]袁明霞,唐荣,周巧玲,等.冬虫夏草对糖尿病肾病大鼠肾组织HIF-1α及VEGF表达的影响[J].中南大学学报:医学版,2013,38(5):448-457.
[22]Cai X,Huang Y,Zhang X,et al.Cloning,characterization,hypoxia and heat shock response of hypoxia inducible factor-1(HIF-1)from the small abalone Haliotis diversicolor[J].Gene,2014,534(2):256.