四妙勇安汤异病同治动脉粥样硬化与血栓闭塞性脉管炎机制研究.docx

四妙勇安汤“异病同治”动脉粥样硬化与血栓闭塞性脉管炎机制研究
 
 
李艺博　张悦健　李娟　童宏选　卢涛
摘要 目的：通过生物信息分析手段探讨四妙勇安汤对动脉粥样硬化（AS）与血栓闭塞性脉管炎（TAO）“异病同治”的潜在分子机制。方法：通过数据库挖掘与检索获取四妙勇安汤中4味中药的活性化合物和对应的靶标;通过GeneCards、比较基因组数据库（CTD）以及美国国家生物技术信息中心（NCBI）数据库筛选AS和TAO的关联靶点;运用Venny ，获得药物作用于二病的共有靶点;基于STRING数据库构建共有靶蛋白的蛋白质-蛋白质相互作用（PPI）网络;通过Cytoscape -活性化合物-共有靶点-疾病整体调控网络图。使用Bioconductor生物信息软件包进行基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）通路富集分析。结果：四妙勇安汤与AS、TAO的共有靶点主要为VEGFA、IL6、JUN、TNF、FOS、MAPK8、MMP9、IL10、ICAM1等计47个;筛选出以黄***类和甾醇类为主的有效活性成分计9个;KEGG通路富集得到的这些靶点共同参与糖尿病并发症AGE-RAGE、TNF、动脉粥样硬化与流体剪切应力、人巨细胞病毒感染、細胞凋亡、T细胞受体等多条通路调节。结论：四妙勇安汤通过抗炎、减少斑块形成、免疫反应、改变血液流变等多条生物学通路发挥药理作用，证实了其多成分、多靶点、多途径的调节特点，预测了四妙勇安汤“异病同治”AS与TAO的潜在分子机制，为实验设计和后续研究提供理论依据。
关键词 四妙勇安汤;动脉粥样硬化;血栓闭塞性脉管炎;异病同治;潜在作用机制;网络药理学
Abstract Objective：To explore the the common key target and signaling pathway of Simiao Yong′an（SMYA） Decoction in treating atherosclerosis and thromboangiitis obliterans by bioinformatic
：The active compounds and corresponding targets of 4 traditional Chinese medicines from SMYA Decoction were obtained by database mining and associated targets of AS and TAO were screened by GeneCards，CTD and NCBI was used to obtain the common targets of the two diseases of drug PPI network of common target proteins was constructed through STRING software was used to construct drug-active compound-common target-disease global regulatory network GO classified enrichment analysis and KEGG pathway enrichment analysis were performed using Bioconductor ：The common targets of SMYA Decoction in As and Tao were mainly 47，including VEGFA，IL6，Jun，TNF，FOS，MAPK8，MMP9，IL10，ICAM1， total of 9 active components，mainly flavonoids and sterols，were screened targets were enriched by KEGG pathway and participate in the regulation of multiple pathways such as AGE-RAGE signaling pathway in diabetic complications，TNF signaling pathway，fluid shear str