山东医药2024，Vol.64Issue(33)：25-29,5.DOI:10.3969/j.issn.1002-266X.2024.33.006
非酒精性脂肪性肝炎代谢相关关键差异表达基因靶向治疗药物的筛选与验证
Screening and validation of targeted therapeutic agents for key differentially expressed genes related to metabolism in non-alcoholic steatohepatitis
摘要
Abstract
Objective To screen and validate targeted therapeutic agents for key differentially expressed genes(DEGs)related to metabolism in non-alcoholic steatohepatitis(NASH),in order to provide a reference for the develop-ment of new drugs for NASH.Methods The NASH gene expression profiles GSE164760 and GSE63067 datasets were downloaded from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified using R software,and GO molecular function and KEGG signaling pathway analyses were performed.The DEGs associat-ed with NASH and metabolic genes were intersected to screen NASH metabolic key DEGs using LASSO regression model and SVM-RFE algorithm.Targeted therapeutic agents for NASH metabolic key DEGs were identified using the Compara-tive Toxicogenomics Database(CTD),Traditional Chinese Medicine Systems Pharmacology Database and Analysis Plat-form(TCMSP),and PubMed database.Molecular docking was conducted using Autodock4 software to verify the targeted relationship between the obtained therapeutic agents and NASH metabolic key DEGs.The effect of naringenin,a NASH metabolic key DEGs targeted therapeutic agent,on the content of intracellular lipid droplets in NASH cells was observed using Oil Red 〇staining.The effect of naringenin on the expression of NASH metabolic key DEGs within NASH cells was observed using real-time quantitative RT-qPCR.Results A total of 336 DEGs were identified,which were mainly involved in fatty acid metabolism,protein targeting,small molecule degradation metabolism,the biosynthesis of auxiliary factors,bile secretion,and peroxisomes,and other signaling pathways.The NASH metabolic key DEGs were identified as SLCO1B1,SCD,and ACAT1 genes.Four compounds,naringenin,cyclosporin,abrine,and chenodeoxycholic acid,were found to target ACAT1,SCD,and SLCO1B1.Molecular docking results indicated that naringenin,cyclosporin,abrine,and chenodeoxycholic acid had good molecular binding activity with ACAT1,SCD,and SLCO1B1 genes,sug-gesting a targeted relationship.Cell experiments demonstrated that the targeted therapeutic agent naringenin could de-crease the content of intracellular lipid droplets in NASH cells and influence the expression of ACAT1,SCD,and SL-CO1B1 genes within NASH cells.Conclusion The targeted therapeutic agents for key DEGs related to metabolism in NASH are naringenin,cyclosporin,abrine,and chenodeoxycholic acid,which are validated by molecular docking and cell experiments.关键词
慢性肝病/非酒精性脂肪性肝病/非酒精性脂肪性肝炎/柚皮素/靶向治疗药物Key words
chronic liver disease/non-alcoholic fatty liver disease/non-alcoholic steatohepatitis/naringenin/tar-geted therapeutic agents分类
医药卫生引用本文复制引用
黄雨晴,王小宁,陆景坤..非酒精性脂肪性肝炎代谢相关关键差异表达基因靶向治疗药物的筛选与验证[J].山东医药,2024,64(33):25-29,5.基金项目
国家自然科学基金项目(81960757,82260813) （81960757,82260813）
内蒙古自治区成果转化项目(2019CG042) （2019CG042）
内蒙古自治区自然科学基金项目(2019MS08119,2020MS08045) （2019MS08119,2020MS08045）
内蒙古医科大学基础项目(YKD2021MS033) （YKD2021MS033）
内蒙古自治区科技计划项目(2023YFDZ0059). （2023YFDZ0059）
