目的 基于分子網(wǎng)絡(luò)研究四逆散治療抑郁癥的潛在生物學(xué)機(jī)制。方法 借助于中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫(kù)和分析平臺(tái)（TCMSP）數(shù)據(jù)庫(kù)篩選四逆散的活性成分，篩選條件為口服利用率、藥物相似性和血腦屏障透過(guò)率，并挖掘四逆散活性成分靶點(diǎn)和抑郁癥的治療靶點(diǎn)。利用韋恩圖找到活性成分靶點(diǎn)和疾病靶點(diǎn)的交集靶點(diǎn)，對(duì)應(yīng)相應(yīng)成分定義為四逆散抗抑郁的有效成分。利用String在線數(shù)據(jù)庫(kù)進(jìn)行交集靶點(diǎn)蛋白質(zhì)-蛋白質(zhì)相互作用網(wǎng)絡(luò)的預(yù)測(cè)，并利用DAVID數(shù)據(jù)庫(kù)進(jìn)行交集靶點(diǎn)KEGG信號(hào)通路的富集分析。最后使用Cytoscape 3.6軟件進(jìn)行活性成分-靶點(diǎn)網(wǎng)絡(luò)及有效成分-靶點(diǎn)-信號(hào)通路的構(gòu)建和拓?fù)浞治觥?b>結(jié)果 篩選出了四逆散107個(gè)有效成分和28個(gè)重要的抗抑郁癥靶點(diǎn)。四逆散抗抑郁癥的重要靶點(diǎn)顯著富集于神經(jīng)活性配體-受體相互作用、5-羥色胺能突觸、多巴胺能突觸、逆行內(nèi)源性大麻素信號(hào)傳導(dǎo)、鈣信號(hào)通路等10個(gè)信號(hào)通路中。結(jié)論 本研究從分子網(wǎng)絡(luò)的角度初步揭示了四逆散治療抑郁癥的潛在作用機(jī)制，其主要的生物學(xué)機(jī)制可能與以神經(jīng)活性配體-受體相互作用為中心的信號(hào)通路有關(guān)。

Objective Based on molecular network, the underlying biological mechanism of Sini Powder in the treatment of depression was studied. Methods Using TCMSP database to screen the active components of Sini Powder, the screening conditions were oral utilization, drug similarity and blood-brain barrier permeability, and the therapeutic targets of Sini Powder and depression were found. The intersections of active component targets and disease targets were found by using Venn diagram, and the corresponding components were defined as effective components of tetrastigmatic anti-depression. A string online database was used to predict the intersecting target protein-protein interaction network, and a DAVID database was used to conduct the enrichment analysis of the KEGG signal pathway of the intersecting target. Finally, Cytoscape 3.6 was used to construct the active componenttarget network and active component-target-signal pathway. Results We screened out 107 active ingredients and 28 important antidepression targets. Antidepressant when one of the important targets significantly enriched in Neuroactive ligand-receptor interaction and Serotonergic synapse, Dopaminergic synapse, Retrograde endocannabinoid signaling, Calcium signaling pathway, etc. 10 in the signal path. Conclusion This study preliminarily revealed the potential mechanism of the therapeutic effect of Sini Powder on depression from the perspective of molecular network, and its main biological mechanism may be related to the signaling pathway centered on the Neuroactive ligand-receptor interaction.

國(guó)家自然科學(xué)基金重點(diǎn)項(xiàng)目（81430102）