[關(guān)鍵詞]
[摘要]
目的 整合用藥網(wǎng)絡與靶點網(wǎng)絡方法分析文獻中治療糖尿病合并冠心病方劑的核心處方及藥理機制,為今后的實驗研究和臨床應用提供一種新的思路。方法 檢索中文文獻來源于中國學術(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)學數(shù)據(jù)庫(VIP)、中國生物醫(yī)學文獻數(shù)據(jù)庫(SinoMed)、web of science、PubMed、Embase、Cochrane Library中收錄治療糖尿病合并冠心病的相關(guān)文獻中的方劑,建立處方-藥物數(shù)據(jù)庫。運用古今醫(yī)案平臺(V2.3.5)進行頻次統(tǒng)計、性味歸經(jīng)分析、關(guān)聯(lián)分析和復雜網(wǎng)絡分析,尋求核心處方。利用Cytoscape 3.9.1軟件構(gòu)建靶點網(wǎng)絡。將有效靶點導入STRING數(shù)據(jù)庫,構(gòu)建蛋白質(zhì)相互作用(PPI)網(wǎng)絡分析;利用Metascape數(shù)據(jù)庫進行基因本體(GO)注釋及京都基因與基因組百科全書(KEGG)通路富集分析。結(jié)果 整理后共得到方劑295首,涉及中藥204味,其中頻次>20次的中藥35味,用藥頻次最高的是丹參;關(guān)聯(lián)規(guī)則發(fā)現(xiàn)藥對黃芪→丹參和黃芪→麥冬的支持度最高;根據(jù)頻數(shù)分析、關(guān)聯(lián)分析、復雜網(wǎng)絡分析結(jié)果以及臨床用藥經(jīng)驗,總結(jié)出治療糖尿病合并冠心病的核心處方:丹參、黃芪、麥冬、川芎、五味子、瓜蔞、當歸、茯苓?,F(xiàn)代中藥化學成分研究發(fā)現(xiàn)該核心處方的關(guān)鍵成分為槲皮素、黃芪紫檀烷苷、山柰酚、木犀草素等,核心靶點AKT1、TP53、IL-6、CASP3、VEGFA、ESR1、HSP90AA1、EGFR、PPARG、STAT3等。GO功能富集通路為激活劑結(jié)合等,KEGG富集通路主要為PI3K-Akt信號通路等。結(jié)論 通過數(shù)據(jù)挖掘,得出文獻中治療糖尿病合并冠心病的核心處方組成為丹參、黃芪、麥冬、川芎、五味子、瓜蔞、當歸、茯苓,其核心成分為槲皮素、黃芪紫檀烷苷、山柰酚等,這些成分通過PI3K-Akt信號通路作用于AKT1、TP53、IL-6、CASP3、VEGFA、ESR1等靶點,為糖尿病合并冠心病的科學研究和臨床治療提供思路。
[Key word]
[Abstract]
Objective Integrating drug network and target network approaches to analyze the core prescriptions and pharmacological mechanisms of prescriptions for the treatment of diabetes mellitus combined with coronary heart disease in the literature, providing a new way of thinking for future experimental studies and clinical applications. Methods The prescriptions in the literature related to the treatment of diabetes mellitus combined with coronary heart disease were searched in CKNI, VIP, Wanfang, SinoMed, web of science, PubMed, Embase and Cochrane Library to build a prescription-drug database. The Ancient and Modern Medical Case Platform (V2.3.5) was used to find the core prescriptions by conducting frequency statistics, nature and flavor attribution analysis, association analysis and complex network analysis. Target networks were constructed using Cytoscape 3.9.1 software. The validated targets were imported into the STRING database to construct protein interaction network analysis. GO enrichment analysis and KEGG pathway enrichment analysis were carried out using the Metascape database. Results After collation, a total of 295 prescriptions were obtained, involving 204 Chinese medicines, of which 35 were used more than 20 times, and the most frequent one was Salviae Miltiorrhizae Radix et Rhizoma, the association rule found the highest support for Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma and Astragali RadixOphiopogonis Radix. Based on the results of frequency analysis, association analysis, complex network analysis and clinical experience in using medicines, the core prescriptions for treating diabetes combined with coronary heart disease were summarized as Salviae Miltiorrhizae Radix et Rhizoma, Astragali Radix, Ophiopogonis Radix, Chuanxiong Rhizoma, Schisandrae Chinensis Fructus, Trichosanthis Fructus, Angelicae Sinensis Radix, and Poria. The key components of this core prescription were found to be quercetin, (3R)-3-(2-hydroxy-3,4-dimethoxyphenyl) chroman-7-ol, kaempferol, luteolin, etc. The core targets were AKT1, TP53, IL-6, CASP3, VEGFA, ESR1, HSP90AA1, EGFR, PPARG, STAT3, etc. The GO functional enrichment pathway were activator binding, etc., and the main KEGG enrichment pathways were the PI3K-Akt signaling pathway, etc. Conclusions Through data mining, it was concluded that the core prescription composition in the literature for the treatment of diabetes combined with coronary heart disease is Salviae Miltiorrhizae Radix et Rhizoma, Astragali Radix, Ophiopogonis Radix, Chuanxiong Rhizoma, Schisandrae Chinensis Fructus, Trichosanthis Fructus, Angelicae Sinensis Radix, and Poria. Their core components are quercetin, astragalus purpureus and kaempferol, which act on AKT1, TP53, IL-6, CASP3, VEGFA, ESR1 and other targets through PI3K-Akt signaling pathway, providing ideas for scientific research and clinical treatment of diabetic combined with coronary heart disease.
[中圖分類號]
R285.5
[基金項目]
國家中醫(yī)藥管理局2021岐黃學者支持項目(國家中醫(yī)藥人教函[2022]6);謝雁鳴全國名老中醫(yī)藥專家傳承工作室建設項目(國家中醫(yī)藥人教函[2022]75)