目的 運(yùn)用網(wǎng)絡(luò)藥理學(xué)和分子對(duì)接的方法研究黃蜀葵花干預(yù)糖尿病腎病的多成分、多靶點(diǎn)、多通路作用機(jī)制，旨在為其基礎(chǔ)研究及臨床應(yīng)用提供依據(jù)。方法 通過(guò)ETCM、HERB數(shù)據(jù)庫(kù)結(jié)合文獻(xiàn)報(bào)道，篩選黃蜀葵花活性成分，并通過(guò)PharmMapper數(shù)據(jù)庫(kù)預(yù)測(cè)其潛在靶點(diǎn)，建立靶點(diǎn)數(shù)據(jù)庫(kù)。通過(guò)Genecards、OMIM、Drugbank、TTD等數(shù)據(jù)庫(kù)篩選糖尿病腎病相關(guān)靶點(diǎn)，應(yīng)用R4.1.0軟件取兩者交集靶點(diǎn)。通過(guò)STRING平臺(tái)獲得蛋白互作（PPI）關(guān)系，并應(yīng)用Cytoscape 3.8.2構(gòu)建PPI網(wǎng)絡(luò)并分析其中關(guān)鍵靶點(diǎn)。通過(guò)David數(shù)據(jù)庫(kù)進(jìn)行基因本體論（GO）和京都基因和基因組百科全書（KEGG）基因富集分析，得到黃蜀葵花干預(yù)糖尿病腎病的潛在作用通路，采用Cytoscape 3.8.2構(gòu)建“成分-作用靶點(diǎn)-通路”調(diào)控網(wǎng)絡(luò)，使用AutoDock Vina 1.1.2軟件進(jìn)行分子對(duì)接驗(yàn)證。結(jié)果 從黃蜀葵花中篩選出43個(gè)活性成分，其中涉及糖尿病腎病作用靶點(diǎn)44個(gè)，Cytoscape分析最終篩選出9個(gè)關(guān)鍵靶點(diǎn)。GO富集分析結(jié)果顯示，根據(jù)P值<0.05，篩選出生物過(guò)程（BP）120個(gè)，細(xì)胞組分（CC）23個(gè)，分子功能（MF）37個(gè)。KEGG富集分析結(jié)果顯示，黃蜀葵花主要作用于腫瘤壞死因子（TNF）、絲裂原活化蛋白激酶（MAPK）等信號(hào)通路。分子對(duì)接結(jié)果顯示，大部分靶點(diǎn)與成分的結(jié)合活性較好。結(jié)論 基于網(wǎng)絡(luò)藥理學(xué)探討了黃蜀葵花干預(yù)糖尿病腎病多成分-多靶點(diǎn)-多通路的作用特點(diǎn)，預(yù)測(cè)黃蜀葵花主要活性成分槲皮素-3-O-刺槐糖苷、蘆丁、槲皮素-3'-O-葡萄糖苷、銀椴苷等，可能通過(guò)白蛋白（ALB）、表皮生長(zhǎng)因子受體（EGFR）、雌激素受體（ESR1）、過(guò)氧化物酶體增值因子活化受體（PPARG）、凝血酶原（prothrombin，F(xiàn)2）等靶點(diǎn)，作用于腫瘤壞死因子TNF、MAPK等信號(hào)通路干預(yù)糖尿病腎臟病，為進(jìn)一步開(kāi)展黃蜀葵花干預(yù)糖尿病腎病作用機(jī)制研究提供了新的思路和方法。

Objective Using the methods of network pharmacology and molecular docking, the mechanism of multicomponent, multitarget and multipathway action of flowers of Abelmoschus manihot in the intervention of diabetic kidney disease was studied, aiming to provide basis for its basic research and clinical application. Methods ETCM and HERB database combined with literature reports were used to screen the active ingredients of flowers of Abelmoschus manihot, and PharmMapper database was used to predict its potential targets and establish target database. Genecards, OMIM, Drugbank, TTD and other databases were used to screen the related targets of diabetic kidney disease, and R4.1.0 software was used to select the intersection targets. Protein interaction (PPI) relationships were obtained using STRING platform, and PPI networks were constructed using Cytoscape3.8.2 and the key targets were analyzed. David database was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) gene enrichment analysis to obtain the potential pathway of flowers of Abelmoschus manihot in the intervention of diabetic kidney disease. Cytoscape 3.8.2 was used to construct the "components-target-pathway" regulatory network. AutoDock Vina 1.1.2 software was used for molecular docking verification. Results Forty-three active components were screened from flowers of Abelmoschus manihot, including 44 targets of diabetic kidney disease, and 9 key targets were screened by Cytoscape analysis. According to the results of GO enrichment analysis, 120 biological processes, 23 cell components, and 37 molecular functions were screened out according to P < 0.05. KEGG enrichment analysis showed that flowers of Abelmoschus manihot mainly acted on tumor necrosis factor (TNF) and mitogen-activated protein kinase (MAPK) signaling pathways. The results of molecular docking showed that most of the targets had good binding activity with the compounds. Conclusion Based on network pharmacology, the effects of multicomponent, multitarget and multipathway on the flowers of Abelmoschus manihot in the intervention of diabetic kidney disease were discussed. The main active components, such as quercetin-3-O-robinobioside, rutin, quercetin 3'-O-glucoside, and tiliroside may act on TNF, MAPK and other signaling pathways through ALB, EGFR, ESR1, PPARG and F2 to intervene diabetic nephropathy. This study provided a new idea and method for further study on the mechanism of the intervention on diabetic kidney disease.

R287.3

湖南省自然科學(xué)基金計(jì)劃資助項(xiàng)目（2018JJ6037）