摘要
目的:基于转录组学与网络药理学技术,探讨黄连解毒汤治疗湿热蕴毒型结直肠癌(colorectal cancer,CRC)的作用机制。方法:将30只BALB/c小鼠随机分为对照组(Control组)、模型组(CRC组)及黄连解毒汤组(HLJDD组,9.01 g·kg^(-1)),每组10只。除Control组外,其余小鼠采用AOM/DSS腹腔注射结合高脂饮食法建立湿热蕴毒型CRC模型。灌胃10周后,采用RNA-Seq技术进行转录组学分析。利用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems pharmacology,TCMSP)检索黄连解毒汤的化学成分和作用靶点。通过GeneCards、TTD、OMIM、DrugBank、PharmGkb数据库筛选CRC的靶点,并获取其与黄连解毒汤的交集靶点。通过Cytoscape 3.8.0软件构建“活性成分-潜在靶点”网络,采用“Network Analyzer”插件进行拓扑分析,筛选黄连解毒汤治疗CRC的关键成分。将转录组学与网络药理学的结果联合分析,得到黄连解毒汤治疗CRC的核心靶点。利用Metascape数据库进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析。结果:与Control组比较,CRC组小鼠结肠肿物数目增加且结肠长度减少(P<0.05);与CRC组比较,HLJDD组小鼠结肠肿物数目减少且结肠长度增加(P<0.05)。转录组学显示,Control组与CRC组比较,得到4117个差异表达基因;HLJDD组与CRC组比较,得到1254个差异表达基因。黄连解毒汤的化学成分65个,作用靶点207个。CRC靶点17045个,其与黄连解毒汤的交集靶点202个。关键成分包括槲皮素、山柰酚、汉黄芩素、黄芩素等。核心靶点包括AR、RUNX1T1、NOS3、HSPB1等。KEGG通路包括HIF-1信号通路、Apelin信号通路、VEGF信号通路等。结论:黄连解毒汤可能通过槲皮素、山柰酚等成分,调控HIF-1、VEGF等信号通路,作用于NOS2、AR、RUNX1T1等靶点,从而发挥抗湿热蕴毒型CRC的作用。
Objective:To investigate the mechanism of Huanglian Jiedu Decoction in the treatment of colorectal cancer(CRC)with Damp-Heat induced Toxin syndrome based on transcriptomics and network pharmacology techniques.Methods:Thirty BALB/c mice were randomly divided into control group(Control group),model group(CRC group)and Huanglian Jiedu Decoction group(HLJDD group,9.01 g·kg^(-1)),with 10 mice in each group.Except for the Control group,the remaining mice were treated with AOM/DSS intraperitoneal injection combined with high-fat diet to establish a damp-heat toxic CRC model.After 10 weeks of gavage,transcriptomic analysis was performed using RNA-Seq technology.The chemical composition and action targets of Coptis detoxification decoction were retrieved by using the Traditional Chinese Medicine Systems pharmacology database and analysis platform(TCMSP).The targets of CRC were screened by GeneCards,TTD,OMIM,DrugBank,and PharmGkb databases,and the intersection targets with Coptis detoxification decoction were obtained.The"active ingredient-potential target"network was constructed through Cytoscape 3.8.0 software,and the"Network Analyzer"plug-in was used for topological analysis to screen the key components of Huanglian Jiedu Decoction for the treatment of CRC.The results of transcriptomics and network pharmacology were combined to obtain the core target of Coptis detoxification decoction in the treatment of CRC.The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was performed using the Metascape database.Results:Compared with the control group,the number of colon masses in the CRC group increased and the length of the colon decreased(P<0.05),and compared with the CRC group,the number of colon masses in the HLJDD group decreased and the length of the colon increased(P<0.05).Transcriptomics showed that 4117 differentially expressed genes were obtained in the Control group compared with the CRC group.A total of 1254 differentially expressed genes were obtained in the HLJDD group and the CRC group.The chemical components of Coptis detoxification decoction are 65 and the target is 207.There were 17045 CRC targets,and 202 intersecting targets with Huanglian Jiedu Decoction.Key ingredients include quercetin,kaempferol,baicalelin,baicalein,etc.The core targets include AR,RUNX1T1,NOS3,HSPB1,etc.KEGG pathways include HIF-1 signaling pathway,Apelin signaling pathway,VEGF signaling pathway,etc.Conclusion:Huanglian Jiedu Decoction may regulate HIF-1,VEGF and other signaling pathways through quercetin and kaempferol,and act on AR,RUNX1T1 and other targets,to play a role in resisting Damp-Heat induced Toxin CRC.
作者
黄闻柏
李鑫煜
陈霭莹
陈海滔
姚庆华
姜靖雯
HUANG Wenbai;LI Xinyu;CHEN Aiying;CHEN Haitao;YAO Qinghua;JIANG Jingwen(Guangzhou University of Traditional Chinese Medicine,Guangzhou Guangdong China 510006;Department of Traditional Chinese Medicine,The People′s Hospital of Sanya,Sanya Hainan China 572000;The Second Affiliated Hospital to Zhejiang Chinese Medical University,Hangzhou Zhejiang China 310005;Department of Oncology,Hainan Hospital,Guangdong Provincial Hospital of Traditional Chinese Medicine,Haikou Hainan China 570100)
出处
《中医学报》
2025年第9期1977-1985,共9页
Acta Chinese Medicine
基金
海南省自然科学基金(高层次人才)项目(819QN358)
海南省自然科学基金面上项目(822RC847)
海南省卫生健康科技创新联合项目(WSJK2024MS178)
海南省卫生健康行业科研项目(22A200292)。
关键词
黄连解毒汤
结直肠癌
湿热蕴毒证
网络药理学
转录组学
小鼠
Huanglian Jiedu Decoction
colorectal cancer
Damp-Heat induced Toxin syndrome
network pharmacology
transcriptomics
mouse
