目的:运用网络药理学与生物信息学方法挖掘四神丸治疗溃疡性结肠炎的作用靶点和相关信号通路,探究该方治疗溃疡性结肠炎的作用机制。方法:通过检索中医药百科全书数据库(ETCM)获取四神丸有效的活性成分及预测靶基因,从基因表达集(GEO)...目的:运用网络药理学与生物信息学方法挖掘四神丸治疗溃疡性结肠炎的作用靶点和相关信号通路,探究该方治疗溃疡性结肠炎的作用机制。方法:通过检索中医药百科全书数据库(ETCM)获取四神丸有效的活性成分及预测靶基因,从基因表达集(GEO)芯片数据库及基因疾病关联数据库(Dis Ge NET),人类孟德尔遗传综合数据库(OMIM),药物靶标数据库(Drug Bank),比较毒物基因组数据库(CTD),遗传药理学与药物基因组学数据库(Pharm GKB)疾病数据库收集溃疡性结肠炎的疾病靶基因,将两者取交集得到药物-疾病蛋白靶基因,并通过Cytoscape软件将结果进行网络化展示,通过网络拓扑算法筛选出作用的关键靶基因,运用基因本体富集分析软件工具包(GOEAST)与注释、可视化和集成发现数据库(DAVID)在线工具对关键靶基因进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,结合相关文献分析四神丸防治溃疡性结肠炎的作用机制。结果:四神丸所含草药的活性成分182个,预测靶标611个;通过疾病数据库检索与溃疡性结肠炎发生发展相关的已知疾病靶标914个;四神丸主要作用于溃疡性结肠炎的类固醇激素介导信号通路、外源代谢过程,RNA聚合酶Ⅱ启动子转录的正调控、脂质代谢过程、细胞氧化剂解毒、信号转导等生物学功能,参与花生四烯酸、药物代谢-细胞色素P450,细胞色素P450对异种生物、化学致癌等关键信号通路。结论:四神丸治疗溃疡性结肠炎具有多靶点、多途径、多层次的特性,其所作用的多条信号通路均存在直接或间接关联性,参与脂质蛋白代谢、药物代谢及抗癌机制等方面,并通过对机体的消化系统、循环系统、免疫系统等多系统综合干预而发挥药效,因此与多因素所诱导的溃疡性结肠炎发病的综合效应机制相吻合。展开更多
Ulcerative colitis(UC) is an inflammatory disease that mainly affects the colon and rectum. It is believed that genetic factors, host immune system disorders, intestinal microbiota dysbiosis, and environmental factors...Ulcerative colitis(UC) is an inflammatory disease that mainly affects the colon and rectum. It is believed that genetic factors, host immune system disorders, intestinal microbiota dysbiosis, and environmental factors contribute to the pathogenesis of UC. however, studies on the role of intestinal microbiota in the pathogenesis of UC have been inconclusive. Studies have shown that probiotics improve intestinal mucosa barrier function and immune system function and promote secretion of anti-inflammatory factors, thereby inhibiting the growth of harmful bacteria in the intestine. Fecal microbiota transplantation(FMT) can reduce bowel permeability and thus the severity of disease by increasing the production of short-chain fatty acids, especially butyrate, which help maintain the integrity of the epithelial barrier. FMT can also restore immune dysbiosis by inhibiting Th1 differentiation, activity of T cells, leukocyte adhesion, and production of inflammatory factors. Probiotics and FMT are being increasingly used to treat UC, but their use is controversial because of uncertain efficacy. Here, we briefly review the role of intestinal microbiota in thepathogenesis and treatment of UC.展开更多
文摘目的:运用网络药理学与生物信息学方法挖掘四神丸治疗溃疡性结肠炎的作用靶点和相关信号通路,探究该方治疗溃疡性结肠炎的作用机制。方法:通过检索中医药百科全书数据库(ETCM)获取四神丸有效的活性成分及预测靶基因,从基因表达集(GEO)芯片数据库及基因疾病关联数据库(Dis Ge NET),人类孟德尔遗传综合数据库(OMIM),药物靶标数据库(Drug Bank),比较毒物基因组数据库(CTD),遗传药理学与药物基因组学数据库(Pharm GKB)疾病数据库收集溃疡性结肠炎的疾病靶基因,将两者取交集得到药物-疾病蛋白靶基因,并通过Cytoscape软件将结果进行网络化展示,通过网络拓扑算法筛选出作用的关键靶基因,运用基因本体富集分析软件工具包(GOEAST)与注释、可视化和集成发现数据库(DAVID)在线工具对关键靶基因进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析,结合相关文献分析四神丸防治溃疡性结肠炎的作用机制。结果:四神丸所含草药的活性成分182个,预测靶标611个;通过疾病数据库检索与溃疡性结肠炎发生发展相关的已知疾病靶标914个;四神丸主要作用于溃疡性结肠炎的类固醇激素介导信号通路、外源代谢过程,RNA聚合酶Ⅱ启动子转录的正调控、脂质代谢过程、细胞氧化剂解毒、信号转导等生物学功能,参与花生四烯酸、药物代谢-细胞色素P450,细胞色素P450对异种生物、化学致癌等关键信号通路。结论:四神丸治疗溃疡性结肠炎具有多靶点、多途径、多层次的特性,其所作用的多条信号通路均存在直接或间接关联性,参与脂质蛋白代谢、药物代谢及抗癌机制等方面,并通过对机体的消化系统、循环系统、免疫系统等多系统综合干预而发挥药效,因此与多因素所诱导的溃疡性结肠炎发病的综合效应机制相吻合。
基金Supported by the National Natural Science Foundation of China,No.81670504 and No.81472287the New Xiangya Talent Project of the Third Xiangya Hospital of Central South University,No.20150308
文摘Ulcerative colitis(UC) is an inflammatory disease that mainly affects the colon and rectum. It is believed that genetic factors, host immune system disorders, intestinal microbiota dysbiosis, and environmental factors contribute to the pathogenesis of UC. however, studies on the role of intestinal microbiota in the pathogenesis of UC have been inconclusive. Studies have shown that probiotics improve intestinal mucosa barrier function and immune system function and promote secretion of anti-inflammatory factors, thereby inhibiting the growth of harmful bacteria in the intestine. Fecal microbiota transplantation(FMT) can reduce bowel permeability and thus the severity of disease by increasing the production of short-chain fatty acids, especially butyrate, which help maintain the integrity of the epithelial barrier. FMT can also restore immune dysbiosis by inhibiting Th1 differentiation, activity of T cells, leukocyte adhesion, and production of inflammatory factors. Probiotics and FMT are being increasingly used to treat UC, but their use is controversial because of uncertain efficacy. Here, we briefly review the role of intestinal microbiota in thepathogenesis and treatment of UC.
