Gene expression profile analysis involved in pathogenesis of allergic rhinitis by using bioinformatics method as a novel way of drug screening
-
摘要: 目的: 探讨变应性鼻炎(AR)发病相关基因表达谱特征,并根据药物与疾病基因表达谱相似性对比的原理,筛选出可能对AR具有治疗作用的潜在新型表观药物。方法: 以AR为关键词,在开放的人类基因表达数据库和基因芯片数据库中检索与AR发病相关的基因表达谱,并进行聚类分析。然后,在药物基因表达谱数据库中筛选与AR发病相关基因表达谱特征相反者。结果: 检索到1个满足条件的相关基因表达数据库GSE43523。与AR发病相关的基因共有11个(表达水平变化超过2倍),其中上调者7个,下调者4个。对AR发病相关基因谱与药物基因表达谱相似性分析发现,嘌呤霉素、脱氧前列腺素J2、泼尼松、苯海索、甲亢平、林可霉素、金鸡纳啶、可可碱、雷公藤和多西拉敏等10种药物都具有治疗AR的作用。结论: 采用生物信息学方法,对比疾病发病相关基因表达谱与药物基因表达谱的相似性,有可能成为AR治疗药物筛选的新方法。Abstract: Objective: In this study, the characteristics of gene expression profiles of allergic rhinitis (AR) were preliminarily explored. Based on the comparison of the similarity between drug and disease gene expression profiles, new drugs that could treat AR were screened out.Method: AR was used as the key word to search gene expression datasets related to pathogenesis of AR in public Gene Expression Omnibus (GEO) of NCBI. After significance test, gene expression profiles involved in pathogenesis of AR were screened and applied to cluster analysis. And then AR related gene expression profiles were thrown into pharmacological gene expression datasets for similarity analysis and significantly negative correlation was used as a screening criterion for potential curative drugs of AR.Result: Only one gene expression dataset was found out, ie GSE43523. Computational bioanalysis identified a total of 11 candidate genes involved in pathogenesis of AR, whose expression level exceeded more than 2-fold. Among them, 7 genes were upregulated and 4 genes were downregulated. Similarity analysis of gene expression profiles of AR showed that puromycin, 15-delta prostaglandin J2, prednisone, trihexyphenidyl, carbimazole, lincomycin, cinchonidine, theobromine, tripterygium wilfordii and doxylamine might have potential therapeutic effects on AR.Conclusion: It is concluded that by means of bioinformatics method, similarity analysis between disease related gene expression and pharmacological gene expression profiles may be a novel way of drug screening for AR.
-
Key words:
- allergic rhinitis /
- bioinformatics /
- drug screening /
-
[1] ZHANG Y, ZHANG L.Prevalence of allergic rhinitis in china[J].Allergy Asthma Immunol Res, 2014, 6:105-113.
[2] 吴湘萍.患者管理方式对变应性鼻炎舌下含服粉尘螨滴剂疗效的影响[J].山东大学耳鼻喉眼学报, 2018, 32 (3):68-72.
[3] 邱前辉.变应性鼻炎免疫治疗的现状和未来[J].临床耳鼻咽喉头颈外科杂志, 2017, 31 (1):9-12.
[4] JACOBSEN L, NIGGEMANN B, DREBORG S, et al.Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma:10-year follow-up on the PAT study[J].Allergy, 2007, 62:943-948.
[5] NIGGEMANN B, JACOBSEN L, DREBORG S, et al.Five-year followup on the PAT study:specific immunotherapy and long-term prevention of asthma in children[J].Allergy, 2006, 61:855-859.
[6] MOLLER C, DREBORG S, FERDOUSI H A, et al.Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study)[J].J Allergy Clin Immunol, 2002, 109:251-256.
[7] DES ROCHES A, PARADIS L, MENARDO J L, et al.Immunotherapy with a standardized Dermatophagoides pteronyssinus extract.VI.Specific immunotherapy prevents the onset of new sensitizations in children[J].J Allergy Clin Immunol, 1997, 99:450-453.
[8] PAJNO G B, BARBERIO G, DE LUCA F, et al.Prevention of new sensitizations in asthmatic children monosensitized to house dust mite byspecific immunotherapy.A six-year follow-up study[J].Clin Exp Allergy, 2001 31:1392-1397.
[9] INAL A, ALTINTAS D U, YILMAZ M, et al.Prevention of new sensitizations by specific immunotherapy in children with rhinitis and/or asthma monosensitized to house dust mite[J].J Investig Allergol Clin Immunol, 2007, 17:85-91.
[10] RONALD J A.Trent.卢学春, 杨波, 张峰, 译.临床生物信息学[M]//北京:军事医学科学出版社, 2014:1-1.
[11] 杨波, 卢学春, 刘丽宏, 等.靶向上调ID4基因表达药物的生物信息学预测和初步验证[J].中华医学杂志, 2009, 89 (24):1714-1716.
[12] 杨波, 卢学春, 迟小华, 等.基于生物信息学分析人类LRP16基因功能初步研究[J].癌症, 2009, 28 (12):1283-1290.
[13] 中国癌症基金会《中国肿瘤临床年鉴》编辑委员会编.2016中国肿瘤临床年鉴[M].北京:中国协和医科大学出版社, 2017:578-579.
[14] 卢学春, 杨波, 朱宏丽, 等.生物信息学方法优化依硫磷酸联合方案治疗骨髓增生异常综合征的应用研究[J].中华医学杂志, 2009, 89 (26):1834-1837.
[15] 杨波, 蔡力力, 迟小华, 等.依硫磷酸调控人类基因表达谱的预测及生物信息学分析[J].中国实验血液学杂志, 2011, 19 (3):711-716.
[16] 卢学春, 迟小华, 杨波, 等.重型再生障碍性贫血发病相关T淋巴细胞基因表达谱的生物信息学分析及作为药物筛选新方法的探索[J].中国实验血液学杂志, 2010, 18 (2):416-420.
[17] 卢学春, 杨波, 迟小华, 等.含盐酸二甲双胍联合方案治疗再生障碍性贫血的短期疗效观察[J].解放军医学杂志, 2012, 37 (3):229-233.
[18] YU R, YANG B, CHI X, et al.Efficacy of cytokine-induced killer cell infusion as an adjuvant immunotherapy for hepatocellular carcinoma:a systematic review and meta-analysis[J].Drug Des Devel Ther, 2017, 11:851-864.
[19] 于睿莉, 杨波, 蔡力力, 等.老年骨髓增生异常综合征的临床病理特征及氨磷汀联合生长因子方案的长期疗效观察[J].中国药物应用与监测, 2017, 14 (2):75-80.
[20] HUANG DA W, SHERMAN B T, LEMPICKI R A.Systematic and integrative analysis of large gene lists using DAVID Bioinformatics Resources[J].Nat Protoc, 2009, 4:44-57.
[21] LAMB J, CRAWFORD E D, PECK D, et al.The Connectivity Map:using gene-expression signatures to connect small molecules, genes, and disease[J].Science, 2006, 313:1929-1935.
[22] LAMB J.The Connectivity Map:a new tool for biomedical research[J].Nat Rev Cancer, 2007, 7:54-60.
[23] SUBRAMANIAN A, NARAYAN R, CORSELLO S M, et al.A Next Generation Connectivity Map:L1000Platform and the First 1, 000, 000Profiles[J].Cell, 2017, 171:1437-1452.e17.
[24] 秦成玉.盐酸苯海索治疗帕金森病及帕金森综合征效果观察[J].临床合理用药杂志, 2017, 10 (10):75-76.
[25] 程芳.小剂量他巴唑治疗70例老年亚临床甲亢的效果[J].中国医药指南, 2016, 14 (32):13-14.
[26] 李文惠, 刘喆.15-脱氧-Δ12, 14-前列腺素J2在脑缺血中的神经保护作用[J].国际脑血管病杂志, 2011, 19 (11):849-852.
[27] 李颖, 陈向东.雷公藤甲素对变应性鼻炎大鼠鼻黏膜组织中核转录因子-κB和诱导型一氧化氮合酶表达的影响[J].郑州大学学报 (医学版), 2008, 43 (2):351-353.
[28] 李颖, 陈向东.雷公藤红素对变应性鼻炎大鼠鼻黏膜组织中NF-κB和Eotaxin表达的影响[J].临床耳鼻咽喉头颈外科杂志, 2012, 26 (20):943-945.
[29] 崔静, 李辉, 王海军.雷公藤红素治疗变应性鼻炎大鼠的机制研究[J].临床耳鼻咽喉头颈外科杂志, 2014, 28 (8):550-553.
计量
- 文章访问数: 110
- PDF下载数: 73
- 施引文献: 0