基于生物信息学途径挖掘防治急性高原病的潜在药物

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英文篇名：Mining potential drugs for prevention and treatment of acute mountain sickness based on bioinformatics approach 作者：施冰 ; 崔庆华 ; 冯振龙 ; 李俊峡 英文作者：Shi Bing;Cui Qinghua;Feng Zhenlong;Li Junxia;Department of Geriatrics,No.7 Medical Center of PLA General Hospital; 关键词：高原病 ; 低氧 ; 计算生物学 ; 药物评价 ; 临床前 ; 数据挖掘 英文关键词：Altitude sickness;;Hypoxia;;Computational Biology;;Drug evaluation,preclinical;;Data mining 中文刊名：LZBJ 英文刊名：Chinese Journal of Clinical Healthcare 机构：中国人民解放军总医院第七医学中心干一科;北京大学医学部生物信息学系;安徽医科大学研究生院; 出版日期：2019-07-02 18:49 出版单位：中国临床保健杂志 年：2019 期：v.22 基金：全军后勤重点项目(BBJ14L001) 语种：中文; 页：LZBJ201904022 页数：5 CN：04 ISSN：34-1273/R 分类号：77-81

摘要

目的应用生物信息学途径挖掘潜在的防治急性高原病的药物。方法选取急性高原低氧暴露7 d大鼠心肌组织标本,进行全转录组高通量测序,筛选差异表达mRNA。应用生物信息学工具Connectivity Map,整合差异表达mRNA信息,推测急性高原低氧心肌损伤差异基因与药物小分子功能的关系,筛选潜在的具有防治急性高原低氧心肌损伤效应的药物。结果高通量测序结果显示,与常压常氧对照组比较,急性高原低氧暴露大鼠心肌组织中1 084个mRNA表达水平发生显著变化。其中457个mRNA表达上调,627个mRNA表达下调。通过connectivity map药物数据库比对分析,发现小分子化合物SB203580负性富集分数较高,是潜在的防治急性高原病的药物。动物实验提示SB203580可减轻高原低氧大鼠心肌水肿和心肌组织病理损伤,下调心肌AQP1mRNA表达。结论通过生物信息学方法可挖掘出潜在的防治急性高原病的药物,研究方法合理、简便、省时,减少了药物开发研究的盲目性。
        Objective To explore potential drugs for prevention and treatment Acute Mountain Sickness by bioinformatics.Methods Myocardial tissue of rats exposed to high altitude hypobaric hypoxia for 7 days was selected for high throughput sequencing to screen differentially expressed genes.Connectivity Map was used to speculate the relationship between differentially expressed genes and function of small molecule drugs,and to screen potential drugs for preventing and treating Acute Mountain Sickness.Results High-throughput sequencing results showed that the expression of 1084 mRNAs in myocardium of rats exposed to high altitude hypobaric hypoxia changed significantly compared with that of normobaric control group.457 mRNAs were upregulated and 627 mRNAs were downregulated.Through the comparative analysis of connectivity map drug database,it was found that SB203580 had higher negative enrichment fraction,and was potential drug to prevent and treat Acute Mountain Sickness.Animal experiments showed that SB203580 could alleviate myocardial edema and pathological damage in rats exposed to high altitude hypobaric hypoxia,and downregulate the expression of AQP1 mRNA in myocardium.Conclusion Potential drugs for prevention and treatment of acute mountain sickness can be excavated by bioinformatics.The research method is reasonable,simple and time saving,which reduces the blindness of drug development and research.

引文

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