摘要
目的探讨某些药物以及所涉及的基因引起马凡综合征的可能机制。方法通过比较毒理基因组学数据库(CTD)分析引起马凡综合征关联的药物及其相互作用的基因。选取药物与马凡综合征高度相关的基因进行基因本体分析和KEGG信号通路等基因富集分析。结果有24种关键基因/蛋白参与凋亡过程的正向调节、血压的负向调节、细胞对有机氮的反应、转化生长因子β信号、多细胞的生物过程、肾脏发育、脂多糖反应等生物学进程,以及与蛋白多糖反应、肾素分泌、激活丝裂原活化蛋白激酶信号通路,其中与基因有关的药物有阿替洛尔、多四环素、氯沙坦、硫代巴比妥酸。结论药物可能通过影响基因表达从而引起某些信号通路的改变等内在分子生物学机制与马凡综合征产生关联,通过分析引起马凡综合征疾病相关基因/蛋白通路,可为临床应用新药、生物疗法和手术疗法提供科学依据。
Objective To investigate the possible mechanism of certain drugs and related genes in the development of Marfan syndrome.Methods The Comparative Toxicogenomics Database(CTD)was used to analyze the drugs and related genes associated with Marfan syndrome,and then the genes highly associated with drugs and Marfan syndrome were used to perform the gene function enrichment analyses including gene ontology and KEGG signaling pathways.Results A total of 24 key genes/proteins were involved in the biological processes including positive regulation of apoptosis,negative regulation of blood pressure,cell response to organic nitrogen,transforming growth factorβsignal,multicellular biological process,kidney development,and reaction to lipopolysaccharide,as well as protein-polysaccharide reaction,renin secretion,and activation of the mitogen-activated protein kinase signaling pathway.Atenolol,tetracycline,losartan,and thiobarbituric acid were associated with genes.Conclusion Some drugs may affect the expression of genes,result in the change in related signaling pathways,and thus lead to Marfan syndrome via such molecular biological mechanisms.An analysis of genes and protein pathways associated with Marfan syndrome can provide a scientific basis for clinical application of new drugs,biological therapies,and surgical treatment.
作者
王天毅
牛兆倬
黄强
生伟
吴建涛
李丹丹
WANG Tianyi;NIU Zhaozhuo;HUANG Qiang;SHENG Wei;WU Jiantao;LI Dandan(Qingdao Municipal Hospital(Group),Qingdao 266001,China)
出处
《青岛大学学报（医学版）》
CAS
2020年第1期35-39,共5页
Journal of Qingdao University(Medical Sciences)
基金
山东省医药卫生科技发展计划项目(2013WS0023)
