山西大学学报（自然科学版）2026，Vol.49Issue(3)：416-429,14.DOI:10.13451/j.sxu.ns.2025133
联合孟德尔随机化与网络药理学筛选酒精性肝病干预策略
Mendelian Randomization and Network Pharmacology Screening for Intervention Strategies of Alcoholic Liver Disease
摘要
Abstract
This study aimed to identify novel therapeutic target genes for alcoholic liver disease(ALD)by employing Mendelian randomization analysis,integrated gene expression database analysis,and network pharmacology methods,providing theoretical foundations for developing novel ALD treatments.First,bidirectional two-sample Mendelian randomization analysis was conducted to evaluate causal relationships between alcohol consumption patterns(current drinkers,former drinkers),current drinking status,and ALD development and single nucleotide polymorphisms significantly associated to ALD were genetically localized.Gene expression validation using Gene Expression Omnibus(GEO)datasets identified differentially expressed genes.Core gene enrichment pathways were analyzed through Reactome database,while drug predictions were performed using DSigDB database,molecular docking,and molecular dynamics simulations.Finally,potential therapeutic strategies for ALD were explored through the Components Contents in Traditional Chinese Medicine(ccTCM)network platform.Transcription factor 4(TCF4)shows significant association with ALD pathogenesis(P=0.038)and plays a key role in hepatic stellate cell activation and Wnt/β-catenin signaling pathways.Four natural compounds-epigallocatechin gallate,apigenin,luteolin,and baicalin-exhibits strong binding activity with TCF4(docking energy<-31.38 kJ/mol;molecular dynamics simulations energy<-41.84 kJ/mol).The results suggest that tea and Zhangqiu celery could serve as dietary interventions for ALD,while Scutellaria baicalensis and aster tataricus represent as potential therapeutic agents.Through Mendelian randomization,GEO differential analysis and network pharmacology methods,this study found that TCF4 is a potential target for the treatment of alcoholic liver disease,suggesting that tea and Zhangqiu celery can be used as dietary intervention ingredients for alcoholic liver disease,while Scutellaria baicalensis Georgi and Aster tataricus display potential medicinal therapeutic value.关键词
膳食选择/中药/转录因子4Key words
dietary selection/traditional Chinese medicine/transcription factor 4分类
医药卫生引用本文复制引用
张荫杰,任晨佳,王婷,王炫琳,丁一帆,舒建宇,张冲,张旭锐,郭华..联合孟德尔随机化与网络药理学筛选酒精性肝病干预策略[J].山西大学学报（自然科学版）,2026,49(3):416-429,14.基金项目
药用资源化学与分子工程国家重点实验室开放课题(CMEMR2023-B15) （CMEMR2023-B15）
中央引导地方科技发展专项资金(YDZJSX2025D081) （YDZJSX2025D081）
国家中医药管理局科技专项(GZY-KJS-2025-115) （GZY-KJS-2025-115）
山西省自然科学基金(202503021211081) （202503021211081）
