基于网络药理学挖掘溃疡性结肠炎“扶正”治则的潜在机制
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摘要
目的:通过数据库检索与网络药理学方法探讨溃疡性结肠炎"扶正"治则的潜在机制。方法:从中医E百数据库检索溃疡性结肠炎相关方剂,检索方式为"主治肠澼/久痢/痢疾",筛选所检索到的处方并进行药物种类、用药频次统计分析,选择溃疡性结肠炎治疗的常用扶正药物。将选择后的扶正药物输入中药系统药理学分析平台检索所有化学成分和作用靶点,构建化合物-靶点相互作用网络图;通过Digsee数据库筛选溃疡性结肠炎相关靶点,构建疾病-靶点相互作用网络图;筛选两个网络图的核心靶点,利用DAVID工具对核心靶点进行富集分析。结果:数据库共检索到溃疡性结肠炎相关方剂731首,根据纳入、排除标准筛选后获得处方304首,中药220味,经用药频次统计后,以甘草、人参、白术为溃疡性结肠炎扶正治则的代表药物。基于药代动力学ADME参数对上述药物的化学成分进行筛选和靶标预测,共得到136个蛋白靶点;将化合物-靶点、疾病-靶点的蛋白质—蛋白质相互作用网络图合并,以"节点连接度""节点介度"和"节点紧密度"为评价标准,筛选共有靶点129个;对入选靶标进行京都基因与基因组百科全书(KEGG)富集分析,以P值筛选出前20条通路在溃疡性结肠炎方面具有作用。结论:扶正药物治疗溃疡性结肠炎作用的发挥是多靶点、多通路的整体效应,挖掘了溃疡性结肠炎扶正治则的潜在机制,为进一步实验研究提供了理论基础。
Objective: Through database search and network pharmacology to explore the potential mechanism of " Fu Zheng" rule of ulcerative colitis. Method: Search for ulcerative colitis related prescriptions from the Chinese medicine E database,Screening the retrieved prescriptions and conducting statistical analysis of the types and frequency of drugs,and selecting the objective drugs for the treatment of ulcerative colitis. Search for the chemical composition and target of drugs on the Digsee platform,then constructing a compound-target interaction network map. Screening for ulcerative colitis related targets through the Digsee database and construct a diseasetarget interaction network map. Filter the core targets of the two network maps and using the DAVID tool to perform enrichment analysis on the core targets. Result: About 731 prescriptions of ulcerative colitis were retrieved from the database,304 prescriptions and 220 Chinese medicines were received based on the inclusion and exclusion criteria.Representative drugs of " Fu Zheng" Rule of ulcerative colitis is Glycyrrhizae Radix et Rhizoma,Ginseng Radix et Rhizoma,Atractylodis Macrocephalae Rhizoma. Screening for chemical constituents of the drug based on ADME parameters,and then target prediction,we received a total of 137 protein targets. Merge the compound-target interaction network map and the disease-target interaction network map,with " Degree " " betweenness " and " closeness" as the evaluation criteria,we found 129 common targets. Perform KEGG enrichment analysis on the selected targets,find out the top 20 pathways with P values has an effect on ulcerative colitis. Conclusion: The role of FuZheng Chinese medicine in the treatment of ulcerative colitis is the overall effect of multiple targets and multiple pathways,excavating the potential mechanism of " Fu Zheng " rule of ulcerative colitis and provide a theoretical basis for further experimental research.
Objective: Through database search and network pharmacology to explore the potential mechanism of " Fu Zheng" rule of ulcerative colitis. Method: Search for ulcerative colitis related prescriptions from the Chinese medicine E database,Screening the retrieved prescriptions and conducting statistical analysis of the types and frequency of drugs,and selecting the objective drugs for the treatment of ulcerative colitis. Search for the chemical composition and target of drugs on the Digsee platform,then constructing a compound-target interaction network map. Screening for ulcerative colitis related targets through the Digsee database and construct a diseasetarget interaction network map. Filter the core targets of the two network maps and using the DAVID tool to perform enrichment analysis on the core targets. Result: About 731 prescriptions of ulcerative colitis were retrieved from the database,304 prescriptions and 220 Chinese medicines were received based on the inclusion and exclusion criteria.Representative drugs of " Fu Zheng" Rule of ulcerative colitis is Glycyrrhizae Radix et Rhizoma,Ginseng Radix et Rhizoma,Atractylodis Macrocephalae Rhizoma. Screening for chemical constituents of the drug based on ADME parameters,and then target prediction,we received a total of 137 protein targets. Merge the compound-target interaction network map and the disease-target interaction network map,with " Degree " " betweenness " and " closeness" as the evaluation criteria,we found 129 common targets. Perform KEGG enrichment analysis on the selected targets,find out the top 20 pathways with P values has an effect on ulcerative colitis. Conclusion: The role of FuZheng Chinese medicine in the treatment of ulcerative colitis is the overall effect of multiple targets and multiple pathways,excavating the potential mechanism of " Fu Zheng " rule of ulcerative colitis and provide a theoretical basis for further experimental research.
引文
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[3]吴东升,曹晖,张彧,等.芍药汤对溃疡性结肠炎大鼠肠黏膜免疫屏障的干预作用[J].中国实验方剂学杂志,2019,25(9):6-11.
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[14]刘三侠,吴俊伟,林永乐.甘草多糖药理作用研究进展[J].中国兽药杂志,2013,47(1):64-67.
[15]于雪妮,冯小刚,张建民,等.人参化学成分与药理作用研究新进展[J].人参研究,2019,1(1):47-51.
[16]黄艳辉,陈二林,王玉洁,等.人参皂苷Rd治疗大鼠溃疡性结肠炎给药途径的研究[J].甘肃医药,2015,34(7):481-484.
[17]景岚,石欣,张波,等.白术对“泻剂结肠”大鼠结肠cKit含量的影响[J].江苏医药,2016,42(14):1544-1546.
[18]尚秋辰.白术多糖对大肠杆菌腹泻模型小鼠肠道黏膜修复机理研究[D].扬州:扬州大学,2017.
[19] WANG C,DUAN H,HE L. Inhibitory effect of atractylenolideⅠon angiogenesis in chronic inflammation in vivo and in vitro[J]. Eur J Pharmcaol,2009,612(1/3):143.
[20]陈琴华,余飞,王红梅,等.白术内酯Ⅰ、Ⅱ、Ⅲ对炎性巨噬细胞细胞因子表达的影响[J].中国药师,2017,20(12):2112-2116.
[21] FANG P Z, HUANG H Y, ZHANG T, et al.Experimental study on PI3K/Akt-mTOR signal pathway mediated ulcerative colitis associated carcinogenesis[J]. Chin J Gastroenterol Hepatol,2015,24(7):802-826.
[2]王一帆,范恒.氧化苦参碱调控Rho A/ROCK信号通路介导溃疡性结肠炎E-cadherin及TGF-β的影响[J].中国实验方剂学杂志,2019,25(6):73-80.
[3]吴东升,曹晖,张彧,等.芍药汤对溃疡性结肠炎大鼠肠黏膜免疫屏障的干预作用[J].中国实验方剂学杂志,2019,25(9):6-11.
[4]黄晓燕,陈广文,陈然,等.中医药治疗溃疡性结肠炎的机制及进展[J].广西中医药,2018,41(5):73-76.
[5]张声生,李乾构,沈洪,等.溃疡性结肠炎中医诊疗共识(2009)[J].中国中西医结合杂志,2010,30(5):527-532.
[6]张声生,沈洪,郑凯,等.溃疡性结肠炎中医诊疗专家共识意见(2017)[J].中华中医药杂志,2017,32(8):3585-3589.
[7]黎琮毅,林才志,胡乃强,等.基于“五脏相关性”探讨溃疡性结肠炎的发病机制[J].辽宁中医杂志,2019,doi:http://kns. cnki. net/kcms/detail/21. 1128. R.20181121. 1005. 002. html.
[8]张良宇,陆为民.徐景藩治疗溃疡性结肠炎经验[J].中医杂志,2018,59(23):1993-1995.
[9]程龙艳,查安生.查安生运用益气解毒化瘀方治疗溃疡性结肠炎经验摭拾[J].国医论坛,2018,33(5):27-28.
[10] WEI M Y,MA Y H,LIU Y Y,et al. Urinary metabolomics study on the anti-inflammation effects of flavonoids obtained from Glycyrrhiza[J]. J Chromatogr B,2018,1086:1-10.
[11]姜雪,孙森凤,王悦,等.甘草药理作用研究进展[J].化工时刊,2017,31(7):25-28.
[12]崔永明.甘草黄酮的分离鉴定、药效及其指纹图谱研究[D].武汉:华中科技大学,2008.
[13] Kudo T,Okamura S,ZHANG Y J,et al. Topical application of glycyrrhizin preparation ameliorates experimentally inducedcolitis in rats[J]. World J Gastroenterol,2011,17(17):2223-2228.
[14]刘三侠,吴俊伟,林永乐.甘草多糖药理作用研究进展[J].中国兽药杂志,2013,47(1):64-67.
[15]于雪妮,冯小刚,张建民,等.人参化学成分与药理作用研究新进展[J].人参研究,2019,1(1):47-51.
[16]黄艳辉,陈二林,王玉洁,等.人参皂苷Rd治疗大鼠溃疡性结肠炎给药途径的研究[J].甘肃医药,2015,34(7):481-484.
[17]景岚,石欣,张波,等.白术对“泻剂结肠”大鼠结肠cKit含量的影响[J].江苏医药,2016,42(14):1544-1546.
[18]尚秋辰.白术多糖对大肠杆菌腹泻模型小鼠肠道黏膜修复机理研究[D].扬州:扬州大学,2017.
[19] WANG C,DUAN H,HE L. Inhibitory effect of atractylenolideⅠon angiogenesis in chronic inflammation in vivo and in vitro[J]. Eur J Pharmcaol,2009,612(1/3):143.
[20]陈琴华,余飞,王红梅,等.白术内酯Ⅰ、Ⅱ、Ⅲ对炎性巨噬细胞细胞因子表达的影响[J].中国药师,2017,20(12):2112-2116.
[21] FANG P Z, HUANG H Y, ZHANG T, et al.Experimental study on PI3K/Akt-mTOR signal pathway mediated ulcerative colitis associated carcinogenesis[J]. Chin J Gastroenterol Hepatol,2015,24(7):802-826.