摘要
目的探究慢性心衰靶向EGR1中药化合物抑制剂的筛选。方法选取基因芯片中慢性心衰患者与健康人差异表达上调最显著的EGR1基因,再以6种治疗药物作为阳性对照,分析其与EGR1的作用模式,并推测拟筛的化合物与阳性对照物是否具有相似的活性。最后取空白组、模型组及巴西苏木素组大鼠血浆,采用质谱技术联合代谢组学Meta X软件对质谱数据进行多元统计分析,寻找出差异代谢物,再基于KEGG数据库进行代谢物通路注释。结果通过SP、XP打分,将最初30000个小分子化合物筛为100个,再通过结合模式评估筛选出巴西苏木素。三组大鼠血浆代谢组学共鉴定出209个差异代谢物,涉及氨基酸类、脂质类、萜类类和黄酮类。整合多组学研究结果,初步证实巴西苏木素可干预慢性心衰。结论靶向EGR1抑制剂的巴西苏木素可基于糖脂及氨基酸代谢紊乱干预慢性心衰,这与苯丙氨酸代谢、酪氨酸合成、2-氧代羧酸代谢相关。
Objective To explore the screening of traditional Chinese medicine inhibitors targeting EGR1 in chronic heart failure.Methods EGR1,the most significantly up-regulated gene in CHF patients and healthy people,is selected in the gene chip,and then 6 therapeutic drugs are used as the positive control.The action mode of EGR1 is analyzed to speculate whether the compounds to be screened have similar activity to the positive control compounds.Finally,the plasma of rats in blank group,model group and Brazilin group are taken,the mass spectrometry technology combined with metabolomics Meta X software is used to conduct multivariate statistical analysis on the mass spectrometry data,look for different metabolites,and then annotate the metabolite pathway based on KEGG database.Results From the first 30000 small molecular compounds,100 compounds are screened by SP and XP,and then the Brazilin is screened by binding mode evaluation.According to the plasma metabolomics statistics of the three groups of rats,209 differential metabolites are obtained,it involves amino acids,lipids,terpenoids and flavonoids.Integration of multi-omics findings,it is preliminarily confirmed that Brazilin can intervene CHF.Conclusion Brazilin targeting EGR1 inhibitor could interfere with CHF based on glucolipid and amino acid metabolism disorders,which are related to phenylalanine metabolism,tyrosine synthesis,and 2-oxygen-carboxylic acid metabolism.
作者
吕李飞
吴俊松
苟江腾
赵成周
徐卫松
李忠宽
贾守宁
祁永福
LYU Li-fei;WU Jun-song;GOU Jiang-teng;ZHAO Cheng-zhou;XU Wei-song;LI Zhong-kuan;JIA Shou-ning;QI Yong-fu(Qinghai Provincial Key Laboratory of Traditional Chinese Medicine Research for Glucolipid Metabolic Diseases,Qinghai University,Xining 810016,China;National Engineering Research Center for Beijing Biochip Technology(CapitalBio),Beijing 102266,China;Tibetan Medicine College,Qinghai University,Xining 810001,China;BGI,Shenzhen 518083,China;Research Insititute,Qinghai Provincial Hospital of Traditional Chinese Medicine,Xining 810012,China)
出处
《现代中药研究与实践》
CAS
2022年第2期87-93,共7页
Research and Practice on Chinese Medicines
基金
青海省高层次卫生人才(中药学领军人才)项目(2018年,2019年)
青海省中藏医药科研创新项目(J2020005)
青海省卫生健康委员会重点项目(2019-wjzd-11)
青海省应用基础研究项目(2016-ZJ-777)
2018年中医药公共卫生服务补助专项“全国中药资源普查项目”(财社〔2018〕43号)
青海省糖脂代谢疾病防控中医药重点实验室开放课题(QHZYY-202101)。
