摘要
目的 基于基因表达综合数据库(GEO)基因芯片结合网络药理学及分子对接技术探讨清热通腑化瘀方治疗急性胰腺炎(AP)的作用机制。方法 通过GEO数据库获取AP的芯片数据,通过R语言数据包获得AP差异表达基因,采用加权基因共表达网络分析、蛋白质—蛋白质相互作用(PPI)网络分析和CIBERSORT算法识别中药的有效成分及与AP的潜在枢纽生物标志物。从TCMSP数据库获得清热通腑化瘀方的活性成分、作用靶点及AP的靶点基因,构建共同靶点基因关系网络及共同靶点基因的PPI网络。利用R语言软件进行GO功能富集分析和KEGG通路富集分析。采用AutoDock Vina软件进行分子对接。结果 获得GSE91035和GSE107610数据集的表达谱,清热通腑化瘀方活性成分143个,清热通腑化瘀方活性成分—AP共同靶点基因130个,核心活性成分有木犀草素、山柰酚、柚皮素、槲皮素、β-谷甾醇,核心靶点涉及肿瘤蛋白p53种属(TP53)、转录激活蛋白3(STAT3)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、myc原癌蛋白(MYC)、B淋巴细胞瘤-2基因(BCL2)等。通过GO与KEGG通路富集分析分别得到2 651条GO条目、181条信号通路。分子对接结果中木犀草素与MYC的结合活性最好。结论 清热通腑化瘀方中的活性化合物可能通过与AP结合作用于TP53、STAT3、AKT1、MYC、BCL2等靶点调节多条信号通路,可能对AP有治疗作用。
Objective To explore the mechanism of Qingre Tongfu Huayu formula in the treatment of acute pancreatitis(AP)based on GEO gene microarray combined with network pharmacology and molecular docking.Methods The microarray data of AP were obtained from the GEO database,and the differentially expressed genes of AP were identified using R language packages,and the weighted gene co-expression network analysis,protein-protein interaction(PPI)network analysis,and CIBERSORT algorithm were used to identify the active ingredients of the traditional Chinese medicines and the potential pivotal biomarkers with AP.The active components and target genes of Qingre Tongfu Huayu formula,as well as the target genes associated with AP,were retrieved from the TCMSP database.A shared target gene interaction network and PPI network of the common target genes were constructed.GO functional enrichment analysis and KEGG pathway enrichment analysis were performed using R language software.Molecular docking was carried out using AutoDock Vina.Results The expression profiles of GSE91035 and GSE107610 datasets were obtained,with 143 active ingredients of Qingre Tongfu Huayu formula,130 common target genes between Qingre Tongfu Huayu formula and AP,the core active components included LUTEOLIN,Kaempferol,naringenin,quercetin andβ-sitosterol.The key targets involved TP53,STAT3,AKT1,MYC and BCL2.The GO and KEGG pathway enrichment analysis yielded 2651 GO entries and 181 signaling pathways,respectively.The molecular docking results showed the best binding activity of luteolin to MYC.Conclusion The active compounds in Qingre Tongfu Huayu formula may exert therapeutic effects on AP by targeting TP53,STAT3,AKT1,MYC and BCL2,thereby regulating multiple signaling pathways.
作者
丁美林
缪春润
万圆圆
董善增
李泽涵
宗阳
DING Meilin;MIAO Chunrun;WAN Yuanyuan;DONG Shanzeng;LI Zehan;ZONG Yang(Dongtai Hospital of Traditional Chinese Medicine,Jiangsu Province,Dongtai 224200,China;不详)
出处
《临床合理用药》
2025年第24期28-32,F0003,共6页
Chinese Journal of Clinical Rational Drug Use
基金
中国中医科学院中医基础理论研究所基本科研业务费自主选题项目(YZX-202309)。
关键词
急性胰腺炎
清热通腑化瘀方
基因表达综合数据库
网络药理学
分子对接
作用机制
Acute pancreatitis
Qingre Tongfu Huayu formula
Gene expression omnibus
Network pharmacology
Molecular docking
Mechanism of action
