目的 運用計算機網(wǎng)絡(luò)藥理學技術(shù)預(yù)測桃核承氣湯治療膿毒癥心肌功能障礙的作用靶點和信號通路，進一步分析其防治膿毒癥心肌功能障礙的基礎(chǔ)和作用機制。方法 運用中藥系統(tǒng)藥理學成分分析平臺Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP）數(shù)據(jù)庫獲取桃核承氣湯的有效成分及作用靶標基因，從GeneCards數(shù)據(jù)庫收集膿毒癥心肌功能障礙的靶標基因，將兩者取交集后得到疾病-藥物蛋白靶基因，運用STRING構(gòu)建蛋白質(zhì)間相互作用網(wǎng)絡(luò)，并通過Cytoscape軟件將結(jié)果進行網(wǎng)絡(luò)可視化展示，通過網(wǎng)絡(luò)結(jié)構(gòu)和節(jié)點間加權(quán)重聯(lián)系的計算分析算法篩選出作用的關(guān)鍵基因。借助Webgestalt在線工具進行疾病-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)庫并結(jié)合文獻學習，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個化合物中有64成分通過20個靶點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)鍵基因主要通過調(diào)控炎癥反應(yīng)、促進細胞存活、抗細胞凋亡、參與能量代謝、病原識別、毒物代謝等路徑，在質(zhì)膜、細胞膜、吞噬細胞、線粒體自噬等分子反應(yīng)中發(fā)揮作用。結(jié)論 網(wǎng)絡(luò)藥理學方法科學預(yù)測桃核承氣湯防治膿毒癥心肌功能障礙的關(guān)鍵靶標及其參與的相關(guān)通路，提示該方劑對膿毒癥心肌功能障礙的防治作用為多靶點、多通路、多選擇的復(fù)雜機制，并且多與抗炎、抗細胞凋亡、促進細胞存活等機制相關(guān)。

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.

R285.5

國家中醫(yī)藥管理局“西學中”骨干人才培訓項目；江蘇省中醫(yī)藥局科技項目（JD2019SZ03）