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OA
Mendelian Randomization and Network Pharmacology Screening for Intervention Strategies of Alcoholic Liver Disease
本研究旨在运用孟德尔随机化分析、基因表达综合数据库数据分析及网络药理学方法,筛选酒精性肝病治疗的新靶点基因,为开发新型治疗酒精性肝病的药物提供理论依据.首先通过双向两样本孟德尔随机化分析,评估饮酒量、现在饮酒、既往饮酒状态与酒精性肝病的因果关联,并对显著关联的单核苷酸多态性进行基因定位;随后利用基因表达综合数据库(Gene Expression Omnibus,GEO)进行表达验证,筛选差异表达基因;借助Reactome数据库解析核心基因富集的生物学通路,并通过DSigDB数据库及分子对接技术、分子动力学模拟进行药物预测;最后结合中药成分含量数据库(Components Contents in Traditional Chinese Medicine,ccTCM)网络平台挖掘潜在干预酒精性肝病的治疗方案.转录因子4(Transcription Factor 4,TCF4)基因经多维度验证与酒精性肝病发病显著相关(P=0.038),且在肝星状细胞激活、Wnt/β-catenin 信号通路中发挥关键作用;表没食子儿茶素没食子酸酯、芹菜素、木犀草素和白杨素等4种天然产物成分与TCF4存在强结合活性(对接结合能均小于-31.38 kJ/mol,分子动力学模拟对接能量均小于-41.84 kJ/mol);结果提示茶叶、章丘芹菜可作为干预酒精性肝病的膳食选择,黄芩、紫菀作为潜在治疗药物.本研究通过孟德尔随机化、GEO差异分析及网络药理学方法,发现TCF4为治疗酒精性肝病的潜在靶点,茶叶与章丘芹菜可作为酒精性肝病的膳食干预食材,黄芩、紫菀则具备潜在药用治疗价值.
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.
张荫杰;任晨佳;王婷;王炫琳;丁一帆;舒建宇;张冲;张旭锐;郭华
山西大学 中医药现代研究中心,山西 太原 030006山西大学 中医药现代研究中心,山西 太原 030006山西大学 中医药现代研究中心,山西 太原 030006山西大学 中医药现代研究中心,山西 太原 030006山西大学 中医药现代研究中心,山西 太原 030006山西大学 中医药现代研究中心,山西 太原 030006山西大学 中医药现代研究中心,山西 太原 030006山西大学 中医药现代研究中心,山西 太原 030006山西财经大学 校医院,山西 太原 030006
医药卫生
膳食选择中药转录因子4
dietary selectiontraditional Chinese medicinetranscription factor 4
《山西大学学报（自然科学版）》 2026 (3)
416-429,14
药用资源化学与分子工程国家重点实验室开放课题(CMEMR2023-B15)中央引导地方科技发展专项资金(YDZJSX2025D081)国家中医药管理局科技专项(GZY-KJS-2025-115)山西省自然科学基金(202503021211081)
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