摘要
目的:基于病证结合理论,运用网络药理学方法探讨附子理中汤联合香砂六君子汤治疗脾肾阳虚型结直肠癌(Colorectal Cancer,CRC)的潜在作用机制。方法:检索中药系统药理数据库和分析平台(TCMSP)数据库,获取附子理中汤合香砂六君子汤的活性成分,查询对应靶点;在Gene Cards、TTD和Drugbank数据库查找脾肾阳虚型CRC的主要靶点;构建药物有效成分、脾肾阳虚证与CRC靶点的交集韦恩图,借助STRING数据库对交集靶点进行蛋白质-蛋白质相互作用网络构建;在Metascape数据库进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。利用Cytoscape 3.7.1软件绘制核心靶点网络图、“复方-成分-靶点-通路-疾病”网络图。结果:筛选获得附子理中汤合香砂六君子汤活性化合物204种,涉及潜在靶点236个,核心活性成分为槲皮素、山柰酚、β-谷甾醇等。从Gene Cards、TTD和Drugbank数据库获得脾肾阳虚证基因1068个,CRC基因1423个,药-证-病交集靶点77个。蛋白质-蛋白质相互作用网络图显示靠前的核心蛋白包括丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、肿瘤抑制蛋白p53(Tumor Protein p53,TP53)、半胱氨酸蛋白酶3(Caspase 3,CASP3)等。GO富集分析获得细胞组分52个、生物过程1546个以及分子功能115个,主要包括膜筏、膜微域等细胞组分,对激素的反应、腺体发育等生物过程,信号受体调节活性、DNA结合转录因子结合等分子功能。KEGG通路171条,主要涉及癌症通路、癌症中的蛋白多糖、肿瘤坏死因子信号通路等。结论:附子理中汤合香砂六君子汤可能是通过槲皮素、山柰酚等活性成分调控癌症通路、肿瘤坏死因子信号通路等途径发挥对脾肾阳虚型CRC的治疗作用。
Objective:Based on the theory of combination of disease and syndrome,to explore the potential mechanism of the Fuzi Lizhong decoction(附子理中汤)and the Xiangsha Liujunzi decoction(香砂六君子汤)in the treatment of spleen and kidney Yang(阳)deficiency type(脾肾阳虚型)colorectal cancer(CRC)with network pharmacology.Methods:The active ingredients of the Fuzi Lizhong decoction and the Xiangsha Liujunzi decoction were obtained by searching TCMSP database platform,and the corresponding target gene were queried.The main targets of insufficiency of both the spleen and the kidney syndrome and CRC were searched in GeneCards,TTD and Drugbank databases.The main targets of spleen and kidney Yang deficiency syndrome and CRC were found in GeneCards,TTD and Drugbank databases.The Venn diagram of the intersection of the effective components of drugs,spleen and kidney Yang deficiency syndrome and CRC target was constructed,and the protein-protein interaction(PPI)network of the intersection target was constructed with the help of STRING database.GO function and KEGG pathway enrichment analysis were performed in Metascape database.Cytascape 3.7.1 software was used to draw the core target network diagram and the network diagram of compound componenttarget-pathway-disease.Results:A total of 204 active compounds were obtained from the Fuzi Lizhong decoction and the Xiangsha Liujunzi decoction,involving 236 potential targets.The core active ingredients were quercetin,kaempferol,β-sitosterol,etc..From GeneCards,TTD and Drugbank databases,and 1068 genes of spleen-kidney Yang deficiency syndrome,and 1423 genes of CRC,and 77 targets of drugsyndrome-disease intersection were obtained.PPI network diagram showed that the top core proteins included AKT1,TP53,CASP3,etc..GO enrichment analysis obtained 52 cell components,and 1546 biological processes,and 115 molecular functions.Mainly including membrane rafts,membrane microdomain and other cellular components,response to hormone,gland development and other biological processes,s
出处
《中医临床研究》
2023年第20期25-30,共6页
Clinical Journal Of Chinese Medicine
基金
国家中医药循证能力提升建设项目(2019XZZX-ZL005)。
关键词
附子理中汤合香砂六君子汤
脾肾阳虚型结直肠癌
网络药理学
病证结合
The Fuzi Lizhong decoction and the Xiangsha Liujunzi decoction
Colorectal cancer
Spleen-kidney Yang deficiency
Network pharmacology
