[關(guān)鍵詞]
[摘要]
目的 運(yùn)用計(jì)算機(jī)網(wǎng)絡(luò)藥理學(xué)技術(shù)預(yù)測(cè)桃核承氣湯治療膿毒癥心肌功能障礙的作用靶點(diǎn)和信號(hào)通路,進(jìn)一步分析其防治膿毒癥心肌功能障礙的基礎(chǔ)和作用機(jī)制。方法 運(yùn)用中藥系統(tǒng)藥理學(xué)成分分析平臺(tái)Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)數(shù)據(jù)庫(kù)獲取桃核承氣湯的有效成分及作用靶標(biāo)基因,從GeneCards數(shù)據(jù)庫(kù)收集膿毒癥心肌功能障礙的靶標(biāo)基因,將兩者取交集后得到疾病-藥物蛋白靶基因,運(yùn)用STRING構(gòu)建蛋白質(zhì)間相互作用網(wǎng)絡(luò),并通過(guò)Cytoscape軟件將結(jié)果進(jìn)行網(wǎng)絡(luò)可視化展示,通過(guò)網(wǎng)絡(luò)結(jié)構(gòu)和節(jié)點(diǎn)間加權(quán)重聯(lián)系的計(jì)算分析算法篩選出作用的關(guān)鍵基因。借助Webgestalt在線工具進(jìn)行疾病-藥物交集靶基因的基因本體論(GO)分析和京都基因與基因組百科全書(KEGG)通路富集分析,并可視化展示。最后利用CTD數(shù)據(jù)庫(kù)并結(jié)合文獻(xiàn)學(xué)習(xí),獲取關(guān)鍵基因于膿毒癥心肌功能障礙的疾病治療作用。結(jié)果 桃核承氣湯的135個(gè)化合物中有64成分通過(guò)20個(gè)靶點(diǎn)與膿毒癥心肌功能障礙相互關(guān)聯(lián)。其中AKT1、HMOX1、JUN、TNF、IL1B、MAPK14、NOS3、PPARG、ICAM1、NOS2、VCAM1、STAT1等關(guān)鍵基因主要通過(guò)調(diào)控炎癥反應(yīng)、促進(jìn)細(xì)胞存活、抗細(xì)胞凋亡、參與能量代謝、病原識(shí)別、毒物代謝等路徑,在質(zhì)膜、細(xì)胞膜、吞噬細(xì)胞、線粒體自噬等分子反應(yīng)中發(fā)揮作用。結(jié)論 網(wǎng)絡(luò)藥理學(xué)方法科學(xué)預(yù)測(cè)桃核承氣湯防治膿毒癥心肌功能障礙的關(guān)鍵靶標(biāo)及其參與的相關(guān)通路,提示該方劑對(duì)膿毒癥心肌功能障礙的防治作用為多靶點(diǎn)、多通路、多選擇的復(fù)雜機(jī)制,并且多與抗炎、抗細(xì)胞凋亡、促進(jìn)細(xì)胞存活等機(jī)制相關(guān)。
[Key word]
[Abstract]
Objective To explore the potential therapeutic targets of Taohe Chengqi Decoction for sepsis-induced myocardial dysfunction based on network pharmacology. Methods The active constituents and target genes of Taohe Chengqi Decoction were screened based on TCMSP and Uniprot database. Target genes of sepsis-induced myocardial dysfunction were screened by gene cards database, and the intersection between the targets associated with the components of Taohe Chengqi Decoction and sepsis-induced myocardial dysfunction was performed and visualized by Venn diagram. Cytoscape software was used to construct ‘a(chǎn)ctive component-target’ interaction network diagram. The same target genes were uploaded to the STRING database, the protein interaction network map (PPI) was constructed, and core genes were screened by using R language. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment of key targets were analyzed using functional enrichment analysis web tool Webgestalt 2019. Results The 64 active components and 20 effective targets of Taohe Chengqi Decoction in the treatment of sepsis-induced myocardial dysfunction were predicted. Core genes in PPI network are RAC-alpha serine/threonine-protein kinase(AKT1), Heme oxygenase 1(HMOX1), Transcription factor AP-1(JUN), etc. GO enrichment analysis shows that it can affect acute inflammatory response, muscle cell proliferation, reactive oxygen species metabolic process, extrinsic apoptotic signaling pathway, etc. Enrichment analysis of KEGG pathway showed that AGE-RAGE signaling pathway in diabetic complications and fluid shear stress and atherosclerosis pathways were the most significant pathways, followed by TNF signaling pathway and Toll-like receptor signaling pathway. Conclusions Based on network pharmacology, Taohe Chengqi Decoction can treat sepsis-induced myocardial dysfunction by multiple targets and multiple pathways, such as anti-inflammatory, anti-apoptosis, promote cell survival.
[中圖分類號(hào)]
R285.5
[基金項(xiàng)目]
國(guó)家中醫(yī)藥管理局“西學(xué)中”骨干人才培訓(xùn)項(xiàng)目;江蘇省中醫(yī)藥局科技項(xiàng)目(JD2019SZ03)