急性胰腺炎基因表达谱芯片的生物信息学分析及药物筛选

董小鹏; 王丽娟; 赵春霖; 张建平; 潘海邦; 易剑锋; 石育弘

doi:10.3969/j.issn.1001-5256.2020.03.033

急性胰腺炎基因表达谱芯片的生物信息学分析及药物筛选

DOI: 10.3969/j.issn.1001-5256.2020.03.033

1. 甘肃中医药大学临床医学院
2. 甘肃中医药大学药学院
3. 甘肃省中药药理与毒理重点实验室
4. 甘肃中医药大学附属医院普外科
5. 甘肃中医药大学

基金项目:

甘肃省高校基本科研业务费项目(2018A-051)；甘肃省第八批自然科学基金计划(1508RJZA019)；甘肃中医药大学中青年科研基金项目(ZQN2016-4)；

详细信息

中图分类号: R576
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出版历程
- 收稿日期: 2019-08-22
- 出版日期: 2020-03-20

A bioinformatics analysis of acute pancreatitis based on gene expression microarray and drug screening

School of Clinical Medicine,Gansu University of Chinese Medicine

Research funding:

摘要

摘要: 目的应用生物信息学方法筛选急性胰腺炎（AP）差异表达基因（DEGs）及相应的候选治疗药物。方法从基因表达数据库（GEO）中下载小鼠AP相关的高通量芯片数据集（GSE109227和GSE65146）,使用GEO2R筛选DEGs。利用DAVID数据库对DEGs进行基因本体功能富集和通路富集分析。在String数据库中建立蛋白-蛋白相互作用关系（PPI）并利用Cytoscape软件进行可视化,筛选出子网络模块和关键基因。预测关键基因相关的miRNAs并通过比较毒物遗传学数据库（CTD）针对关键基因进行治疗药物的筛选。结果从高通量芯片数据集GSE109227和GSE65146中共筛选到130个上调基因和16个下调基因。DEGs主要参与炎症反应、中性粒细胞趋化、TNF介导的细胞反应、正调控基因表达等生物学过程,且参与细胞外基质受体相互作用、肌动蛋白细胞骨架的调控、白细胞内皮迁移、Focal adhesion等信号通路。在PPI网络中,共筛选出12个关键基因和6个子网络模块。miR-199a-5p、miR-1-3p等miRNAs可能作用于关键基因转录后调控。CTD数据库中筛选到染料木黄酮、白藜芦醇...
- 胰腺炎,急性坏死性 /
- 基因芯片 /
- 基因表达 /
- 计算生物学
Abstract: Objective To screen out differentially expressed genes( DEGs) and related candidate therapeutic drugs for acute pancreatitis( AP) using the bioinformatics method. Methods High-throughput microarray datasets( GSE109227 and GSE65146) associated with AP in mice were downloaded from gene expression omnibus,and GEO2 R was used to screen out DEGs. Database for Annotation,Visualization and Integrated Discovery was used to perform gene ontology and pathway enrichment analysis. Protein-protein interaction( PPI) was established in String database and visualized by Cytoscape,and then subnetwork modules and hub genes were screened out. The microRNAs associated with the hub genes were predicted and candidate drugs were screened out using Comparative Toxicogenomics Database( CTD).Results A total of 130 upregulated and 16 downregulated DEGs were screened out in the high-throughput microarray datasets GSE109227 and GSE65146. DEGs were mainly involved in the biological processes such as inflammatory response,neutrophil chemotaxis,tumor necrosis factor-mediated cellular response,and positive regulation of gene expression,and they were also involved in the signaling pathways of extracellular matrix-receptor interaction,regulation of actin cytoskeleton,leukocyte transendothelial migration,and focal adhesion. A total of 12 hub genes and 6 subnetwork modules were screened out in the PPI network. The microRNAs including miR-199 a-5 p and miR-1-3 p might regulate the post-transcriptional regulation of key genes. Genistein,resveratrol,and quercetin which were screened out from CTD database could reduce the expression of key genes. Conclusion Related genes screened out by the bioinformatics method may play an important role in the development of AP and can be used as the basis for drug screening.
- pancreatitis,acute necrotizing /
- gene microarray /
- gene expression /
- computational biology

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参考文献(28)

[1] SADEK AS,KHATTAB RT. The protective role of melatonin on L-arginine-induced acute pancreatitis in adult male albino rats[J]. Folia Morphol(Warsz),2017,76(1):66-73.

[2] KOLLI S,MASLAK D. Contrast-induced thrombosis in acute mild pancreatitis[J]. Cureus,2019,11(5):e4692.

[3] DIAKOPOULOS KN,ALGUL H. New wine into old wineskins:PGC-1αand NF-κB in obesity and acute pancreatitis[J]. J Pathol,2019,248(1):6-8.

[4] LIU G,TAO J,ZHU Z,et al. The early prognostic value of inflammatory markers in patients with acute pancreatitis[J]. Clin Res Hepatol Gastroenterol,2019,43(3):330-337.

[5] LIU SC,ZHOU J,LEI T. The effect of chinese angelica and peony powder combined with traditional Chinese medicine on the treatment of acute pancreatitis[J]. Chin J Integr Trad West Med Dig,2019,27(8):608-612.(in Chinese)刘世超，周军，雷霆．当归芍药汤加减联合中药外敷治疗急性胰腺炎效果[J]．中国中西医结合消化杂志，2019,27(8):608-612.

[6] YANG GH,ZHAO WX. Early traditional Chinese medicine treatment of acute pancreatitis and its mechanism[J]. J Clin Hepatol,2018,34(4):710-715.(in Chinese)杨国红，赵文霞．急性胰腺炎早期中医药干预与机理探析[J]．临床肝胆病杂志，2018,34(4):710-715.

[7] BARRETT T,WILHITE SE,LEDOUX P,et al. NCBI GEO:Archive for functional genomics data sets-update[J]. Nucleic Acids Res,2013,41(Database issue):d991-d995.

[8] NORBERG KJ,NANIA S,LI X,et al. RCAN1 is a marker of oxidative stress,induced in acute pancreatitis[J]. Pancreatology,2018,18(7):734-741.

[9] HUANG DW,SHERMAN BT,LEMPICKI RA. Systematic and integrative analysis of large gene lists using DAVID Bioinformatics Resources[J]. Nature Protoc,2009,4(1):44-57.

[10] SZKLARCZYK D,GABLE AL,LYON D,et al. STRING v11:Protein-protein association networks with increased coverage,supporting functional discovery in genome-wide experimental datasets[J]. Nucleic Acids Res,2019,47:d607-d613.

[11] SHANNON P,MARKIEL A,OZIER O,et al. Cytoscape:A software environment for integrated models of biomolecular interaction networks[J]. Genome Research,2003,13(11):2498-2504.

[12] KAIMAL V,BARDES EE,TABAR SC,et al. ToppCluster:A multiple gene list feature analyzer for comparative enrichment clustering and network-based dissection of biological systems[J]. Nucleic Acids Res,2010,38(Web Server issue):w96-w102.

[13] DAVIS AP,GRONDIN CJ,JOHNSON RJ,et al. The comparative toxicogenomics database:Update 2019[J]. Nucleic Acids Res,2019,47(D1):d948-d954.

[14] MADHI R,RAHMAN M,TAHA D,et al. Targeting peptidylarginine deiminase reduces neutrophil extracellular trap formation and tissue injury in severe acute pancreatitis[J]. J Cell Physiol,2019,234(7):11850-11860.

[15] LIAO W,TANG YC,ZHOU TT,et al. Effect of miR-423-5p on the injury of AR42J cells induced by caerulein through targeting AQP1[J]. Chin J Clin Pharmacol Ther,2019,24(12):1394-1401.(in Chinese)廖伟，汤玉成，周婷婷，等．miR-423-5p靶向水通道蛋白1对雨蛙肽诱导的急性胰腺炎AR42J细胞损伤的影响[J]．中国临床药理学与治疗学，2019,24(12):1394-1401.

[16] HUTCHINSON JP,ROWLAND P,TAYLOR MRD,et al. Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase[J].Nat Commun,2017,8:15827.

[17] YANG R,TENHUNEN J,TONNESSEN TI. HMGB1 and histones play a significant role in inducing systemic inflammation and multiple organ dysfunctions in severe acute pancreatitis[J]. Int J Inflam,2017,2017:1817564.

[18] JIANG XL,TONG CX,SONG YH. Immunopathogenesis of acute pancreatitis[J]. Chin J Immun,2019,35(4):496-499,504.(in Chinese)姜晓玲，童晨曦，宋银宏．急性胰腺炎的免疫发病机制[J]．中国免疫学杂志，2019,35(4):496-499,504.

[19] LI CY,LIU RX,YIN CZ. The role of autophagy in the development and progression of acute pancreatitis[J]. J Clin Hepatol,2019,35(5):1157-1160.(in Chinese)李春云，刘瑞霞，阴赪宏．自噬在急性胰腺炎发生发展中的作用[J]．临床肝胆病杂志，2019,35(5):1157-1160.

[20] HE DG. Bioinformatics study on genes associated with gonadotropin pituitary adenoma[D]. Lanzhou:Lanzhou University,2018.(in Chinese)何栋钢．促性腺激素垂体腺瘤相关基因的生物信息学研究[D]．兰州:兰州大学，2018.

[21] YUAN HY. Drug target analysis and drug discovery of triplenegative breast cancer via bioinformatics methods[D]. Beijing:Academy of Military Sciences,2018.(in Chinese)袁寒玉．基于生物信息学的三阴乳腺癌靶点分析和药物发现[D]．北京:军事科学院，2018.

[22] AWLA D,ABDULLA A,SYK I,et al. Neutrophil-derived matrix metalloproteinase-9 is a potent activator of trypsinogen in acinar cells in acute pancreatitis[J]. J Leukoc Biol,2012,91(5):711-719.

[23] MARTIROSYAN A,DEL GIUDICE M,BENA CE,et al. Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs[J]. Methods Mol Biol,2019,1912:367-409.

[24] MORAN Y,AGRON M,PRAHER D,et al. The evolutionary origin of plant and animal microRNAs[J]. Nat Ecol Evol,2017,1(3):27.

[25] QIAN XF,GUO Z,HU CJ,et al. Effects of resveratrol on serum inflammatory cytokines in rats with severe acute pancreatitis[J]. Med J Chin PAPF,2013,24(11):948-950,953.(in Chinese)骞秀芳，郭喆，胡常菊，等．白藜芦醇对重症急性胰腺炎大鼠炎性细胞因子的影响[J]．武警医学，2013,24(11):948-950,953.

[26] SUN FL,TENG YS,SHANG D. Mechanisms of action of emodin and resveratrol in severe acute pancreatitis:A comparison[J]. World Chin J Dig,2015,23(27):4376-4383.(in Chinese)孙发律，滕勇生，尚东．大黄素与白藜芦醇治疗重症急性胰腺炎的作用机制对比及其展望[J]．世界华人消化杂志，2015,23(27):4376-4383.

[27] ZHENG JY,ZENG Y,WU JH,et al. Effect of different doses of quercetin on pancreaticpathology in rats with hypertriglyceridemia related acute pancreatitis[J]. World Chin J Dig,2015,23(20):3195-3202.(in Chinese)郑俊媛，曾悦，吴江红，等．不同剂量槲皮素对高甘油三酯血症相关性急性胰腺炎大鼠胰腺病理的影响[J]．世界华人消化杂志，2015,23(20):3195-3202.

[28] XU XW,YANG XM,WANG FH,et al. Effects of quercetin on Toll-like receptor 4/NF-κB signal pathway in alveoar polymorphonucler neutrophil from rats with severe acute pancreatitis-associated lung injury[J]. J Hepatopancreatobiliary Surg,2015,27(1):30-33.(in Chinese)徐晓武，杨小敏，王飞海，等．槲皮素对重症急性胰腺炎相关性肺损伤肺泡中性粒细胞TLR4/NF-κB通路的影响[J]．肝胆胰外科杂志，2015,27(1):30-33.

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