[關(guān)鍵詞]
[摘要]
目的 探討銀屑病使用清熱解毒類方劑治療的用藥規(guī)律,預(yù)測(cè)清熱解毒類方治療銀屑病的常用藥物組合,針對(duì)最常用藥物組合,分析其單用及合用的擅治證型和臨床常用劑量,并探討其分用與合用治療銀屑病的潛在作用機(jī)制,為臨床用藥提供依據(jù)。方法 檢索中國學(xué)術(shù)期刊全文數(shù)據(jù)庫(CNKI)、萬方數(shù)據(jù)庫(Wanfang Data)、維普生物醫(yī)學(xué)數(shù)據(jù)庫(VIP)和PubMed數(shù)據(jù)庫中使用清熱解毒類方治療銀屑病的相關(guān)文獻(xiàn),并對(duì)文獻(xiàn)處方中所用的中藥進(jìn)行頻數(shù)、聚類及關(guān)聯(lián)分析,基于關(guān)聯(lián)規(guī)則,選擇具有較高置信度和較高支持度的藥物組合,檢索篩選其活性成分和靶點(diǎn),并進(jìn)行基因本體(GO)功能富集和京都基因與基因組百科全書(KEGG)通路富集分析。結(jié)果 經(jīng)過檢索,根據(jù)納入和排除標(biāo)準(zhǔn),共納入文獻(xiàn)162篇,包含處方129首,涉及中藥159味,累計(jì)使用頻次1 448次,生地黃、土茯苓、赤芍、牡丹皮、甘草等高頻藥物21味,其中以清熱藥、苦寒藥居多,大多歸入肝經(jīng);關(guān)聯(lián)分析得到支持度最高、關(guān)聯(lián)性較強(qiáng)的藥物組合為“生地黃-赤芍”;聚類分析得到3個(gè)聚類。網(wǎng)絡(luò)藥理學(xué)得到生地黃的潛在活性成分17個(gè),與銀屑病相關(guān)靶點(diǎn)79個(gè),赤芍的潛在活性成分15個(gè),與銀屑病相關(guān)的靶點(diǎn)91個(gè),“生地黃-赤芍”與銀屑病相關(guān)的靶點(diǎn)114個(gè),“生地黃-赤芍”所富集的信號(hào)通路包含了兩者共有的多條經(jīng)典信號(hào)通路,主要涉及癌癥相關(guān)通路、脂質(zhì)與動(dòng)脈粥樣硬化通路、磷脂酰肌醇-3-羥激酶(PI3K)/蛋白激酶B(Akt)信號(hào)通路、缺氧誘導(dǎo)因子(HIF)-1信號(hào)通路、絲裂原活化蛋白激酶(MAPK)信號(hào)通路、Th17細(xì)胞分化通路等。結(jié)論 清熱解毒類方治療銀屑病中的核心藥物組合為生地黃-赤芍,單用可能通過不同的信號(hào)通路來治療單一證型銀屑病,組合使用則可能通過多個(gè)成分干預(yù)多個(gè)靶點(diǎn)、進(jìn)而調(diào)控多條銀屑病相關(guān)的信號(hào)通路來對(duì)不同證型或多證型的銀屑病發(fā)揮治療作用。
[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.
[中圖分類號(hào)]
R285.5
[基金項(xiàng)目]
王新陸全國名中醫(yī)傳承工作室項(xiàng)目(魯財(cái)社指[2018]52號(hào));國家重點(diǎn)研發(fā)計(jì)劃項(xiàng)目(SQ2017YFC170600);山東中醫(yī)藥大學(xué)中醫(yī)藥經(jīng)典理論教育部重點(diǎn)實(shí)驗(yàn)室項(xiàng)目;山東省自然科學(xué)基金資助項(xiàng)目(ZR2022QH185)