目的 基于網(wǎng)絡(luò)藥理學(xué)和分子對(duì)接的方法研究丹參酮II_A治療糖尿病腎病的分子的機(jī)制。方法 利用Swiss Target Prediction、TCMSP、PharmMapper、GeneCards平臺(tái)預(yù)測(cè)丹參酮II_A的作用靶點(diǎn)，從OMIM、DrugBank、TTD、GeneCards數(shù)據(jù)庫中篩選獲得糖尿病腎病的相關(guān)靶點(diǎn)。將得到的丹參酮II_A的作用靶點(diǎn)與疾病靶點(diǎn)取交集得到潛在靶點(diǎn)，構(gòu)建蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)，并通過網(wǎng)絡(luò)拓?fù)浞治龊Y選核心靶點(diǎn)。采用Metascape平臺(tái)分析對(duì)交集靶點(diǎn)進(jìn)行基因本體（GO）功能富集分析與京都基因與基因組百科全書（KEGG）通路富集分析。最后運(yùn)用AutoDock Vina 1.1.2對(duì)丹參酮II_A和核心靶點(diǎn)之間進(jìn)行分子對(duì)接驗(yàn)證。結(jié)果 共篩選出96個(gè)丹參酮II_A調(diào)控糖尿病腎病的潛在靶點(diǎn)，通過網(wǎng)絡(luò)拓?fù)浞治鲋械亩龋╠egree）值篩選出白蛋白（ALB）、蛋白激酶B1（AKT1）、白細(xì)胞介素-6（IL-6）、血管內(nèi)皮生長(zhǎng)因子（VEGFA）、腫瘤壞死因子（TNF）、腫瘤蛋白p53（TP53）、絲裂原激活蛋白激酶8（MAPK8）、胱天蛋白酶3（CASP3）8個(gè)核心靶點(diǎn)；GO富集分析篩選出活性氧代謝過程、細(xì)胞遷移的正向調(diào)節(jié)、氧化應(yīng)激反應(yīng)、細(xì)胞死亡的正向調(diào)節(jié)等20個(gè)生物學(xué)過程，KEGG富集篩選出流體剪切應(yīng)力和動(dòng)脈粥樣硬化通路、腫瘤壞死因子信號(hào)通路、叉頭轉(zhuǎn)錄因子（FoxO）信號(hào)通路、VEGF等20條通路。分子對(duì)接驗(yàn)證結(jié)果顯示，核心靶點(diǎn)與丹參酮II_A之間均有良好的結(jié)合活性。結(jié)論 本研究表明丹參酮II_A可能通過多靶點(diǎn)、多通路調(diào)控糖尿病腎病。

Objective To study the molecular mechanism of tanshinone II_A in treatment of diabetic nephropathy based on bioinformatics and molecular docking methods. Methods The Swiss Target Prediction, TCMSP, PharmMapper, and GeneCards platforms were used to predict the target of tanshinone II_A, and the relevant targets of diabetic nephropathy were screened from OMIM, DrugBank, TTD, and GeneCards databases. Target of tanshinone II_A was intersected with the disease target to obtain potential target, and the protein interaction (PPI) network was constructed, and the core target was screened by network topology analysis. Metascape platform was used for gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for intersection targets. Finally, AutoDock Vina 1.1.2 was used to verify the molecular docking between tanshinone II_A and the core target. Results A total of 96 potential targets of tanshinone II_A regulating diabetic nephropathy were selected. Albumin (ALB), protein kinase B1 (AKT1), interleukin 6 (IL-6), vascular endothelial growth factor (VEGFA), tumor necrosis factor (TNF), tumor protein p53 (TP53), mitogen-activated protein kinase 8 (MAPK8) and cysts were screened by degree value in network topology analysis 8 core targets of protease 3 (CASP3). GO enrichment analysis screened out 20 biological processes, including active oxygen metabolism, positive regulation of cell migration, oxidative stress response, and positive regulation of cell death. KEGG enrichment screened 20 pathways including fluid shear stress and atherosclerosis pathway, tumor necrosis factor signaling pathway, FoxO signaling pathway and VEGF pathway. The results of molecular docking showed that the core target had good binding activity with tanshinone II_A. Conclusion This study suggests that tanshinone II_A may regulate diabetic nephropathy through multi-target and multi-pathway.

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國(guó)家自然科學(xué)基金面上項(xiàng)目（8197141539）；國(guó)家自然科學(xué)基金青年基金項(xiàng)目（8200153422，8200153377）