[关键词]
[摘要]
目的 探讨银屑病使用清热解毒类方剂治疗的用药规律,预测清热解毒类方治疗银屑病的常用药物组合,针对最常用药物组合,分析其单用及合用的擅治证型和临床常用剂量,并探讨其分用与合用治疗银屑病的潜在作用机制,为临床用药提供依据。方法 检索中国学术期刊全文数据库(CNKI)、万方数据库(Wanfang Data)、维普生物医学数据库(VIP)和PubMed数据库中使用清热解毒类方治疗银屑病的相关文献,并对文献处方中所用的中药进行频数、聚类及关联分析,基于关联规则,选择具有较高置信度和较高支持度的药物组合,检索筛选其活性成分和靶点,并进行基因本体(GO)功能富集和京都基因与基因组百科全书(KEGG)通路富集分析。结果 经过检索,根据纳入和排除标准,共纳入文献162篇,包含处方129首,涉及中药159味,累计使用频次1 448次,生地黄、土茯苓、赤芍、牡丹皮、甘草等高频药物21味,其中以清热药、苦寒药居多,大多归入肝经;关联分析得到支持度最高、关联性较强的药物组合为“生地黄-赤芍”;聚类分析得到3个聚类。网络药理学得到生地黄的潜在活性成分17个,与银屑病相关靶点79个,赤芍的潜在活性成分15个,与银屑病相关的靶点91个,“生地黄-赤芍”与银屑病相关的靶点114个,“生地黄-赤芍”所富集的信号通路包含了两者共有的多条经典信号通路,主要涉及癌症相关通路、脂质与动脉粥样硬化通路、磷脂酰肌醇-3-羟激酶(PI3K)/蛋白激酶B(Akt)信号通路、缺氧诱导因子(HIF)-1信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、Th17细胞分化通路等。结论 清热解毒类方治疗银屑病中的核心药物组合为生地黄-赤芍,单用可能通过不同的信号通路来治疗单一证型银屑病,组合使用则可能通过多个成分干预多个靶点、进而调控多条银屑病相关的信号通路来对不同证型或多证型的银屑病发挥治疗作用。
[Key word]
[Abstract]
Objective To explore the rules of medication for psoriasis using heat-clearing and detoxifying prescriptions, and predicted the commonly used drug combinations for the treatment of psoriasis. For the most commonly used drug combinations, the syndrome types and clinical dosages commonly used in the treatment of psoriasis alone and in combination were analyzed, in order to provide a basis for clinical use. Methods The relevant documents of the use of heat-clearing and detoxifying prescriptions in CNKI, VIP, Wanfang data and PubMed databases were retrieved, and frequency, clustering and associated analysis of the Chinese medicine used in the document prescription were analyzed. Based on related rules, core drugs with higher confidence and high support were chosed, and core drugs-active ingredients-intersection target network diagram were established, and a series of analysis, including the enrichment of genetic entity functions and Kyoto Analysis of genes and genome encyclopedia were conducted. Results After screening, 162 articles were included, including 129 prescriptions, involving 159 Chinese medicine flavors, and a total frequency of 1 448 times. High-frequency Chinese materia medica such as Rehmanniae Radix, Smilacis Glabrae Rhizoma, Paeoniae Radix Rubra, Moutan Cortex, Glycyrrhizae Radix et Rhizoma were 21 flavors, among which heat-clearing drugs and bitter-cold drugs were in the majority, mostly classified into the liver meridian. The associated analysis has been paired with the most supportive and confident drugs to be "Rehmanniae Radix-Paeoniae Radix Rubra". Classification analysis obtained three clustering class. Network pharmacology yielded 17 potential active components of Rehmanniae Radix with 79 anti-psoriasis targets, 15 potential active components of Paeoniae Radix Rubra with 91 anti-psoriasis targets, and 114 " Rehmanniae Radix -Paeoniae Radix Rubra " anti-psoriasis targets. Interestingly, among the potential active ingredients of the drugs, Rehmanniae Radix and Paeoniae Radix Rubra had only one common component, but the signaling pathways enriched by "Rehmanniae Radix-Paeoniae Radix Rubra" including multiple classical signaling pathways, mainly involving in cancer-related pathways, lipids and atherosclerotic pathways, phospholipidsitol-3-hydroxykinase-protein kinase B signaling pathway, hypoxia-induciblefactor-1 signaling pathway, mitogen activated protein kinases signal pathway, TH17 cell differentiation pathway. Conclusion The core drug combination in the treatment of psoriasis by clearing heat and removing toxins is Rehmanniae Radix and Paeoniae Radix Rubra. Rehmanniae Radix or Paeoniae Radix Rubra alone treated single syndrome psoriasis through multiple signaling pathways. two combined played a therapeutic role in the treatment of different or multiple syndromes psoriasis by interfering with multiple targets through multiple components, and then modulate multiple psoriasis-related signaling pathways.
[中图分类号]
R285.5
[基金项目]
王新陆全国名中医传承工作室项目(鲁财社指[2018]52号);国家重点研发计划项目(SQ2017YFC170600);山东中医药大学中医药经典理论教育部重点实验室项目;山东省自然科学基金资助项目(ZR2022QH185)