目的 采用網(wǎng)絡藥理學及分子對接技術(shù)探討丹參治療缺血性腸病的作用機制。方法 運用TCMSP數(shù)據(jù)庫獲得丹參的有效成分和預測靶點，并在UniProt數(shù)據(jù)庫中進行標準化處理，從而獲得相應的藥物靶點基因。利用GeneCards和OMIM數(shù)據(jù)庫獲得缺血性腸病的靶點基因。將藥物的靶點基因及疾病的靶點基因?qū)腠f恩圖制作分析平臺獲得丹參治療缺血性腸病的潛在作用靶點。利用Cytoscape3.8.2軟件構(gòu)建“藥物–成分–靶點–疾病”網(wǎng)絡。將潛在的作用靶點導入STRING數(shù)據(jù)庫進行蛋白質(zhì)相互作用（PPI）網(wǎng)絡分析。運用Metascape數(shù)據(jù)庫對潛在作用靶點進行基因本體（GO）功能富集分析和京都基因與基因組百科全書（KEGG）通路分析。最后運用AutoDock vina、PyMOL等軟件對丹參有效化學成分和關(guān)鍵的靶點基因進行對接驗證。結(jié)果 共獲得了65個丹參的活性化合物成分，139個丹參的作用靶點基因和2 799個缺血性腸病的作用靶點基因，其中丹參與缺血性腸病共同作用靶點為84個。構(gòu)建網(wǎng)絡發(fā)現(xiàn)木犀草素、丹參酮II_A、新隱丹參酮II等為丹參作用于缺血性腸病的主要化合物成分。通過PPI網(wǎng)絡分析發(fā)現(xiàn)蛋白激酶B1（Akt1）、腫瘤壞死因子（TNF）、雌激素受體1（ESR1）、原癌基因（JUN）和溶質(zhì)載體家族6成員3（SLC6A3）等為關(guān)鍵的靶點基因。富集結(jié)果顯示細胞對氮化合物的反應、細胞對有機環(huán)化合物的反應和細胞對有機氮化合物的反應等生物學過程調(diào)控脂質(zhì)與動脈粥樣硬化、流體剪切應力與動脈粥樣硬化、磷脂酰肌醇3激酶（PI3K）/Akt信號通路、環(huán)鳥苷酸–蛋白激酶G（cGMP-PKG）信號通路、TNF信號通路等信號通路對缺血性腸病起到治療作用。分子對接的結(jié)果表明丹參的有效化學成分和缺血性腸病的靶點基因具有良好的結(jié)合性。結(jié)論 丹參可能通過木犀草素、丹參酮II_A、新隱丹參酮II等有效成分，作用于Akt1、TNF和ESR1等核心靶點基因，調(diào)控脂質(zhì)與動脈粥樣硬化、流體剪切應力與動脈粥樣硬化等信號通路對缺血性腸病起到治療作用。

Objective To investigate the mechanism of action of Salvia miltiorrhiza in treatment of ischemic enteropathy by using network pharmacology and molecular docking technology. Methods The active components and predicted targets of Salvia miltiorrhiza were obtained by TCMSP database, and standardized in UniProt database to obtain the corresponding drug target genes. Target genes of ischemic bowel disease were obtained by GeneCards and OMIM databases. Drug target genes and disease target genes were introduced into the Venn diagram analysis platform to obtain potential targets of Salvia miltiorrhiza in treatment of ischemic bowel disease. Build a “Drug-ingredient-target-disease” network using Cytoscape3.8.2 software. Potential targets were imported into STRING database for protein interaction (PPI) network analysis. Metascape database was used for GO functional enrichment analysis and KEGG pathway analysis for potential targets. Finally, AutoDock vina, PyMOL and other software were used to analyze and verify the effective chemical components and key target genes of Salvia miltiorrhiza. Results A total of 65 active compounds of Salvia miltiorrhiza, 139 target genes of Salvia miltiorrhiza and 2 799 target genes of ischemic bowel disease were obtained, among which 84 target genes of Salvia miltiorrhiza and ischemic bowel disease were combined. Network construction revealed that luteolin, tanshinone II_A, and neocryptotanshinone II were the main compound components of Salvia miltiorrhiza acting in ischemic bowel disease. Akt1, TNF, ESR1, JUN, and SLC6A3 were identified as key target genes by PPI network analysis. The enrichment results showed that biological processes such as cellular response to nitrogen compounds, cellular response to organocyclic compounds, and cellular response to organic nitrogen compounds regulated lipids and atherosclerosis, fluid shear stress and atherosclerosis, PI3K/Akt signaling pathway, cGMP PKG signaling pathway, and TNF signaling pathway signaling pathways play a therapeutic role in ischemic bowel disease. The results of molecular docking indicated that the active chemical components of Salvia miltiorrhiza and the target genes of ischemic enteropathy have good binding. Conclusion Salvia miltiorrhiza may act on core target genes such as Akt1, TNF, and ESR1 to regulate lipids and atherosclerosis, fluid shear stress and atherosclerosis, through the active ingredients such as luteolin, tanshinone II_A and neocryptotanshinone II and other signaling pathways play a therapeutic role in ischemic bowel disease.

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深圳市龍崗區(qū)經(jīng)濟與科技發(fā)展專項資金醫(yī)療衛(wèi)生科技計劃項目(LGWJ2021-75)