目的:通过网络药理学方法预测小陷胸汤治疗冠心病靶标并分析其作用特征,构建"成分-靶标-通路"网络药理模型,揭示小陷胸汤治疗冠心病的潜在通路机制。方法:中药系统药理学数据库与分析平台(TCMSP)获得药物有效成分,Swiss靶标...目的:通过网络药理学方法预测小陷胸汤治疗冠心病靶标并分析其作用特征,构建"成分-靶标-通路"网络药理模型,揭示小陷胸汤治疗冠心病的潜在通路机制。方法:中药系统药理学数据库与分析平台(TCMSP)获得药物有效成分,Swiss靶标预测数据库(Swiss Target Prediction)反向药效团匹配法预测"小陷胸汤-冠心病"靶标;治疗靶标数据库(TTD),Drugbank,疾病-基因网数据库(Dis Ge NET)取美国食品和药物管理局(FDA)批准的冠心病并集靶标。韦恩图获得相关交集,GEO2R在线分析靶标特征,Funrich version 3软件分析生物过程,运用插件Reactome FI对靶标通路富集分析,采用Cytoscape软件构建"成分-靶标-通路"网络。结果:网络分析表明,小陷胸汤治疗冠心病是通过25个治疗成分调控24个靶标,通过GEO2R在线多个基因芯片分析,靶标存在上下调差异,上调靶标11个,下调靶标13个,作用于4大生物过程,21条具体通路。结论:小陷胸汤治疗冠心病的机制可能是通过黄连生物碱类和黄酮类、半夏的核苷类和有机酸类、瓜蒌的豆甾醇类和黄酮类参与基因表达、新陈代谢、蛋白质代谢等生物过程,调节相关靶蛋白的基因表达,调控基因转录通路、生物氧化反应和脂类和脂蛋白代谢、胰岛素样生长因子结合蛋白(IGFBPs)对胰岛素样生长因子(IGF)转运和摄取、细胞外基质的降解等信号通路。展开更多
Objective:To evaluate the efficacy and safety of blood-letting therapy(BLT)in treatment of hypertension.Methods:A comprehensive electronic and manual bibliographic searches were performed in Cochrane Central Register ...Objective:To evaluate the efficacy and safety of blood-letting therapy(BLT)in treatment of hypertension.Methods:A comprehensive electronic and manual bibliographic searches were performed in Cochrane Central Register of Controlled Trials,Excerpt Medica Database(EMBASE),PubMed,China National Knowledge Infrastructure,Chinese Scientific Journal Database,Chinese Biomedical Literature Database,and Wanfang Database to identify randomized controlled trials(RCTs)in which hypertensive patients were treated with BLT or BLT plus antihypertensive drugs(BPAD)against placebo,no treatment or antihypertensive drugs.The Cochrane Risk Assessment Tool was used to assess the methodological quality of trials.The Review Manager 5.3 software was used for meta-analysis.Results:A total of 7 RCTs with 637 hypertensive patients from 1989 to 2017 were identified.Compared with antihypertensive drugs,blood pressure was significantly reduced by BLT(RR=1.21,95%CI:1.01 to 1.44,P=0.03;heterogeneity:P=0.06,I^2=60%)and BPAD(RR=1.25,95%CI,1.02 to 1.53,P=0.03;heterogeneity:P=0.01,I^2=71%).Moreover,a significant improvement in Chinese medicine syndrome by BLT(RR=1.32;95%CI:1.14 to 1.53,P=0.0002;heterogeneity:P=0.53,I^2=0%)and BPAD(RR=1.47;95%CI:1.06 to 2.04,P=0.02;heterogeneity:P=0.13,I^2=56%)was identified.The reported adverse effects were well tolerated.Conclusions:Although some positive findings were identified,no definite conclusions regarding the efficacy and safety of BLT as complementary and alternative approach for treatment of hypertension could be drew due to the generally poor methodological design,significant heterogeneity,and insufficient clinical data.Further rigorously designed trials are warranted to confirm the results.展开更多
文摘目的:通过网络药理学方法预测小陷胸汤治疗冠心病靶标并分析其作用特征,构建"成分-靶标-通路"网络药理模型,揭示小陷胸汤治疗冠心病的潜在通路机制。方法:中药系统药理学数据库与分析平台(TCMSP)获得药物有效成分,Swiss靶标预测数据库(Swiss Target Prediction)反向药效团匹配法预测"小陷胸汤-冠心病"靶标;治疗靶标数据库(TTD),Drugbank,疾病-基因网数据库(Dis Ge NET)取美国食品和药物管理局(FDA)批准的冠心病并集靶标。韦恩图获得相关交集,GEO2R在线分析靶标特征,Funrich version 3软件分析生物过程,运用插件Reactome FI对靶标通路富集分析,采用Cytoscape软件构建"成分-靶标-通路"网络。结果:网络分析表明,小陷胸汤治疗冠心病是通过25个治疗成分调控24个靶标,通过GEO2R在线多个基因芯片分析,靶标存在上下调差异,上调靶标11个,下调靶标13个,作用于4大生物过程,21条具体通路。结论:小陷胸汤治疗冠心病的机制可能是通过黄连生物碱类和黄酮类、半夏的核苷类和有机酸类、瓜蒌的豆甾醇类和黄酮类参与基因表达、新陈代谢、蛋白质代谢等生物过程,调节相关靶蛋白的基因表达,调控基因转录通路、生物氧化反应和脂类和脂蛋白代谢、胰岛素样生长因子结合蛋白(IGFBPs)对胰岛素样生长因子(IGF)转运和摄取、细胞外基质的降解等信号通路。
基金Supported by the National Natural Science Foundation of China(No.81403375)
文摘Objective:To evaluate the efficacy and safety of blood-letting therapy(BLT)in treatment of hypertension.Methods:A comprehensive electronic and manual bibliographic searches were performed in Cochrane Central Register of Controlled Trials,Excerpt Medica Database(EMBASE),PubMed,China National Knowledge Infrastructure,Chinese Scientific Journal Database,Chinese Biomedical Literature Database,and Wanfang Database to identify randomized controlled trials(RCTs)in which hypertensive patients were treated with BLT or BLT plus antihypertensive drugs(BPAD)against placebo,no treatment or antihypertensive drugs.The Cochrane Risk Assessment Tool was used to assess the methodological quality of trials.The Review Manager 5.3 software was used for meta-analysis.Results:A total of 7 RCTs with 637 hypertensive patients from 1989 to 2017 were identified.Compared with antihypertensive drugs,blood pressure was significantly reduced by BLT(RR=1.21,95%CI:1.01 to 1.44,P=0.03;heterogeneity:P=0.06,I^2=60%)and BPAD(RR=1.25,95%CI,1.02 to 1.53,P=0.03;heterogeneity:P=0.01,I^2=71%).Moreover,a significant improvement in Chinese medicine syndrome by BLT(RR=1.32;95%CI:1.14 to 1.53,P=0.0002;heterogeneity:P=0.53,I^2=0%)and BPAD(RR=1.47;95%CI:1.06 to 2.04,P=0.02;heterogeneity:P=0.13,I^2=56%)was identified.The reported adverse effects were well tolerated.Conclusions:Although some positive findings were identified,no definite conclusions regarding the efficacy and safety of BLT as complementary and alternative approach for treatment of hypertension could be drew due to the generally poor methodological design,significant heterogeneity,and insufficient clinical data.Further rigorously designed trials are warranted to confirm the results.