溃疡性结肠炎差异表达基因及中药预测的生物信息学分析

胡宗仁1 郑文江2 严倩2 胡卫维3 孙晓生1

(1.广州中医药大学基础医学院, 广东广州 510006)
(2.广州中医药大学第一临床医学院, 广东广州 510405)
(3.广州中医药大学热带医学研究所, 广东广州 510405)

【摘要】通过生物信息学技术分析比较溃疡性结肠炎(UC)患者与健康人的基因芯片数据,初步筛选UC的差异表达基因,进而预测治疗UC的潜在中药药物。从基因表达数据库(GEO)下载GSE36807基因芯片,使用R语言分析得到上调和下调的差异表达基因,通过String数据库、Cytoscape软件及其插件分析得到差异表达基因的核心基因,对核心基因进行基因本体及京都基因与基因组百科全书分析,通过核心基因与医学本体信息检索平台(Coremine Medical)相互映射,筛选治疗UC的中药。筛选出648个差异表达基因,包括251个下调基因和397个上调基因。上调差异表达基因共得出15个核心基因,包括CXCL8,IL1B,MMP9,CXCL1,CXCL10,CXCL9,CXCL2,CXCL5,TIMP1,CXCL11,STAT1,LCN2,IL1RN,MMP1,IDO1;其生物过程与通路主要富集在白细胞介素、趋化因子配体和细胞因子、趋化因子介导的信号通路,与炎症反应、防御反应、细胞趋化性、分泌颗粒、IL17信号通路、Toll样受体信号通路、NOD样受体信号通路、TNF信号通路等密切相关。治疗UC的潜在中药药物有姜黄、黄连、黄芩、石斛、地榆、黄柏、白及、苍术等。差异表达基因和核心基因的分析促进了对UC发病机制的理解,该研究为UC中药干预的新药开发提供了潜在基因靶标与研发思路。

【关键词】 溃疡性结肠炎; 差异表达基因; 核心基因; 基因本体(GO); 京都基因与基因组百科全书(KEGG); 蛋白质-蛋白质相互作用; 中药预测;

【DOI】

【基金资助】 国家自然科学基金项目(8197151189)

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    References

    [1] 中国中西医结合学会消化系统疾病专业委员会.溃疡性结肠炎中西医结合诊疗共识意见(2017年)[J].中国中西医结合消化杂志,2018,26(2):105.

    [2] ORDAS I,ECKMANN L,TALAMINI M,et al.Ulcerative colitis[J].Lancet,2012,380(9853):1606.

    [3] RUBIN D T,ANANTHAKRISHNAN A N,SIEGEL C A,et al.ACG clinical guideline:ulcerative colitis in adults[J].Am J Gastroenterol,2019,114(3):384.

    [4] 张玉洁,梁洁,吴开春.炎症性肠病诊断与治疗的共识意见(2018年,北京)溃疡性结肠炎部分解读[J].中华消化杂志,2018,38(5):312.

    [5] LAHARIE D.Towards therapeutic choices in ulcerative colitis[J].Lancet,2017,390(10090):98.

    [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.

    [7] MONTERO-MELENDEZ T,LLOR X,GARCIA-PLANELLA E,et al.Identification of novel predictor classifiers for inflammatory bowel disease by gene expression profiling[J].PLoS ONE,2013,8(10):e76235.

    [8] SZKLARCZYK D,MORRIS J H,COOK H,et al.The STRING database in 2017:quality-controlled protein-protein association networks,made broadly accessible[J].Nucleic Acids Res,2017,45(D1):D362.

    [9] CHIN C H,CHEN S H,WU H H,et al.cytoHubba:identifying hub objects and sub-networks from complex interactome[J].BMC Syst Biol,2014,8(Suppl 4):S11.

    [10] BADER G D,HOGUE C W.An automated method for finding molecular complexes in large protein interaction networks[J].BMC Bioinformatics,2003,4:2.

    [11] YU G,WANG L G,HAN Y,et al.clusterProfiler:an R package for comparing biological themes among gene clusters[J].OMICS,2012,16(5):284.

    [12] ITO K,MURPHY D.Application of ggplot2 to pharmacometric graphics[J].CPT Pharmacometrics Syst Pharmacol,2013,2:e79.

    [13] SAITO Y A.The role of genetics in IBS[J].Gastroenterol Clin North Am,2011,40(1):45.

    [14] SARTOR R B.Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases[J].Am J Gastroenterol,1997,92(12 Suppl):5S.

    [15] RUBIN D T,HUO D,KINNUCAN J A,et al.Inflammation is an independent risk factor for colonic neoplasia in patients with ulcerative colitis:a case-control study[J].Clin Gastroenterol Hepatol,2013,11(12):1601.

    [16] FISHER R C,BELLAMKONDA K,ALEX M L,et al.Disrupting inflammation-associated cxcl8-cxcr1 signaling inhibits tumorigenicity initiated by sporadic- and colitis-colon cancer stem cells[J].Neoplasia,2019,21(3):269.

    [17] DINARELLO C A.Interleukin-1 in the pathogenesis and treatment of inflammatory diseases[J].Blood,2011,117(14):3720.

    [18] MANICONE A M,MCGUIRE J K.Matrix metalloproteinases as modulators of inflammation[J].Semin Cell Dev Biol,2008,19(1):34.

    [19] LAKATOS G,HRITZ I,VARGA M Z,et al.The impact of matrix metalloproteinases and their tissue inhibitors in inflammatory bowel diseases[J].Dig Dis,2012,30(3):289.

    [20] JAKUBOWSKA K,PRYCZYNICZ A,JANUSZEWSKA J,et al.Expressions of matrix metalloproteinases 2,7,and 9 in carcinogenesis of pancreatic ductal adenocarcinoma[J].Dis Markers,2016,doi:10.1155/2016/9895721.

    [21] MAO J W,HE X M,TANG H Y,et al.Protective role of metalloproteinase inhibitor (AE-941) on ulcerative colitis in rats[J].World J Gastroenterol,2012,18(47):7063.

    [22] 王晓娣,董恩钰.白介素-17在溃疡性结肠炎表达的研究[J].中华消化杂志,2001,21(11):29.

    [23] BAUMGART D C,CARDING S R.Inflammatory bowel disease:cause and immunobiology[J].Lancet,2007,369(9573):1627.

    [24] SANCHEZ-MUNOZ F,FONSECA-CAMARILLO G,VILLEDA-RAMIREZ M A,et al.Transcript levels of Toll-like receptors 5,8 and 9 correlate with inflammatory activity in ulcerative colitis[J].BMC Gastroenterol,2011,11:138.

    [25] WANG Y,TANG Q,DUAN P,et al.Curcumin as a therapeutic agent for blocking NF-kappaB activation in ulcerative colitis[J].Immunopharmacol Immunotoxicol,2018,40(6):476.

    [26] 朱立伟,朱达坚.姜黄素治疗溃疡性结肠炎的研究进展[J].医学理论与实践,2019,32(5):657.

    [27] ZHU L,GU P,SHEN H.Protective effects of berberine hydrochloride on DSS-induced ulcerative colitis in rats[J].Int Immunopharmacol,2019,68:242.

    [28] XIE S Z,SHANG Z Z,LI Q M,et al.Dendrobium huoshanense polysaccharide regulates intestinal lamina propria immune response by stimulation of intestinal epithelial cells via Toll-like receptor 4[J].Carbohydr Polym,2019,222:115028.

    [29] 耿玲,杨国堂,张旭强,等.紫地榆提取物对慢性溃疡性结肠炎大鼠的治疗作用[J].中药新药与临床药理,2019,30(6):653.

    [30] 郑子春,沈洪,朱萱萱,等.黄柏、地榆、白及对溃疡性结肠炎大鼠组织中NF-κB和细胞因子表达的影响[J].中国中医急症,2010,19(3):469.

    [31] 宁海容,陈建文,刘慰华,等.苍术合剂抗大鼠溃疡性结肠炎的作用及抗氧化机制研究[J].中山大学学报:医学科学版,2008,29(S1):169.

    [32] 马旭冉,王彦礼,邹迪新,等.黄芩汤调控Nrf2通路对溃疡性结肠炎大鼠氧化应激作用的影响[J].药学学报,2019,54(4):653.

    [33] 钟宇,郑学宝,叶华,等.芍药汤对溃疡性结肠炎大鼠TLR4/NF-κB通路的影响[J].中国中药杂志,2019,44(7):1450.

    [34] 王凤仪,赵党生,蒲晓薇,等.芍药汤对湿热内蕴型溃疡性结肠炎大鼠模型结肠组织中AP-1,TNF-α表达的影响[J].中国实验方剂学杂志,2019,25(16):7.

    [35] 王晓妹,田歌,段强军,等.白头翁汤正丁醇提取物对白念珠菌定植下溃疡性结肠炎小鼠的作用机制研究[J].中国中药杂志,2018,43(14):2979.

    [36] 钟宇,郑学宝,叶华,等.白头翁汤对溃疡性结肠炎大鼠的疗效及免疫机制的影响[J].中国实验方剂学杂志,2019,25(12):15.

    [37] 徐洋洋,蔡皓,段煜,等.白术芍药散治疗溃疡性结肠炎研究进展[J].中国中药杂志,2017,42(5):856.

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ISSN:1001-5302

CN: 11-2272/R

Vol 45, No. 07, Pages 1684-1690

April 2020

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摘要

  • 1 资料与方法
  • 2 结果
  • 3 讨论
  • 参考文献