论文部分内容阅读
目的:运用网络药理学方法预测黄连解毒汤抗Hp感染的主要有效成分、靶点及信号通路，挖掘其潜在作用机制，为后续实验研究提供依据。方法:应用TCMSP筛选黄连解毒汤中黄连、黄芩、黄柏、栀子4味中药的主要有效成分及其潜在作用靶点。通过GeneCards数据库和人类孟德尔遗传数据库（OMIM）筛选Hp感染相关靶点，并取药物和疾病的交集靶点。将交集靶点导入Cytoscape 3.7.2构建有效成分和Hp感染相关靶点网络，并进行拓扑学分析。应用STRING在线分析平台构建靶蛋白相互作用（PPI）网络并进行分析。运用R语言在线检索Bioconductor平台对靶点进行GO功能富集；通过DAVID 数据库对靶点进行KEGG通路富集分析。结果:黄连解毒汤中共筛选出85个有效成分，主要包括槲皮素、小檗碱、山柰酚、汉黄芩素、黄芩素等。对应靶点112个，疾病相关靶点1 960个，药物疾病共同靶点71个。网络中度值最高的有效成分为槲皮素，度值最高的靶点为环加氧酶1（PTGS1）。PPI网络中69个节点中度值较高的靶蛋白包括半胱氨酸蛋白酶3（CASP3）、IL6、MAPK8、原癌基因（MYC）、VEGFA、表皮生长因子受体（EGFR）等。GO功能富集分析共获得89个条目，KEGG通路富集分析共筛选12条存在显著差异的信号通路，其中发挥主要作用的有癌症通路、ErbB信号通路、p53信号通路、凋亡、黏附斑等。结论:黄连解毒汤可通过多成分、多靶点、多通路发挥对Hp的治疗作用，可通过抗肿瘤机制调控胃癌进程，本研究可为其有效成分研究和抗Hp机制研究提供依据。“,”Objective:To predict the main active constituent, targets and signaling pathways of n Huanglian-Jiedu Decoction against Helicobacter pylori infection by using network pharmacology, and to explore its potential mechanism, so as to provide objective foundation for the following experimental research.n Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to screen the main active constituent and potential targets of n Coptidis Rhizoma, n Scutellaria baicalensis, n Phellodendri Chinensis Cortex and n Gardeniae Fructus in n Huanglian-Jiedu Decoction. The targets related to Helicobacter pylori infection were screened by GeneCards suite database and human Mendelian genetic database (OMIM), and the intersection of Chinese herbs and disease targets was obtained. The Intersecting target were import into Cytoscape 3.7.2 to construct the network of active constituents and targets related to Helicobacter pylori infection. The protein protein interaction (PPI) network was constructed and analyzed by using string online analysis platform. Use R language to search Bioconductor platform online to enrich go function of targets. The enrichment of KEGG pathway was analyzed by David database.n Results:total of 85 active constituent were screened from n Huanglian-Jiedu Decoction, including quercetin, berberine, kaempferol, wogonin and baicalein. There are 112 corresponding targets, 1 960 disease-related targets and 71 common targets for herbal medicine and disease. Quercetin is the active constituent with the highest degree in the network diagram, and the target with the highest degree is cyclooxygenase-1 (PTGS1). In 69 nodes of PPI graph, the target proteins with the highest degree included CASP3, IL6, MAPK8, MYC, VEGFA and EGFR. A total of 89 items were obtained by GO functional enrichment analysis, and 12 signaling pathways with significant differences were screened by KEGG pathway enrichment analysis. Among them, pathways in cancer, ErbB Signal pathway, p53 signal pathway, apoptosis, and focal adhesion, which play a major role.n Conclusions:Huanglian-Jiedu Decoction may treatm Helicobacter pylori with multi-component, multi-target and multi-pathway charateristics. At the same time, it may regulate the process of gastric cancer through anti-tumor mechanism, which could lay a foundation for the study of active components and anti-HP mechanism.n