目的 利用網(wǎng)絡藥理學及分子對接的方法探究養(yǎng)血清腦丸治療偏頭痛的潛在作用機制并對其進行實驗驗證。方法 利用TCMSP和Swiss Target Prediction數(shù)據(jù)庫篩選養(yǎng)血清腦丸的活性成分和作用靶點，從NCBI GENE、OMIM、CTD、DisGeNET數(shù)據(jù)庫獲取與偏頭痛密切相關的靶點，將其與養(yǎng)血清腦丸靶點取交集后獲得養(yǎng)血清腦丸治療偏頭痛的潛在作用靶點；利用STRING數(shù)據(jù)庫進行蛋白互作網(wǎng)絡（PPI）分析，結(jié)合Cytoscape 3.6.0軟件篩選關鍵靶點；采用DAVID數(shù)據(jù)庫對養(yǎng)血清腦丸治療偏頭痛的潛在作用靶點進行基因本體（GO）和京都基因與基因組百科全書（KEGG）通路富集分析，并采用Cytoscape 3.6.0軟件構(gòu)建“養(yǎng)血清腦丸–組方中藥–活性成分–偏頭痛–靶點–通路”網(wǎng)絡和篩選關鍵成分，使用AutoDock軟件對關鍵成分與關鍵靶點進行分子對接。采用硝酸甘油誘導的偏頭痛大鼠模型，對網(wǎng)絡藥理學研究結(jié)果中的部分關鍵靶點進行實驗驗證。結(jié)果 篩選獲得養(yǎng)血清腦丸活性成分140個、作用靶點279個，其中與偏頭痛治療相關的靶點53個；通過網(wǎng)絡分析，篩選獲得白細胞介素-6（IL-6）、溶質(zhì)載體家族6成員4（SLC6A4）、腫瘤壞死因子（TNF）、血管內(nèi)皮生長因子A（VEGFA）、內(nèi)皮型一氧化氮合酶（NOS3）等靶點、異紫堇杷明堿、槲皮素、斯氏紫堇堿、球紫堇堿、山柰酚等成分可能是養(yǎng)血清腦丸治療偏頭痛的關鍵靶點和關鍵成分，分子對接結(jié)果表明關鍵成分和關鍵靶點間具有較好的結(jié)合活性；KEGG通路富集結(jié)果表明養(yǎng)血清腦丸可能通過神經(jīng)活性配體受體相互作用、5-羥色胺能突觸、鈣信號通路、cAMP信號通路及腫瘤壞死因子信號通路等途徑發(fā)揮治療偏頭痛的作用。動物實驗結(jié)果表明，養(yǎng)血清腦丸能抑制偏頭痛大鼠血清中一氧化氮（NO）、IL-6、TNF-α及腦組織中VEGF表達的升高，促進腦組織5-羥色胺（5-HT）水平的升高和5-羥色胺受體1B（5-HT1B）蛋白的表達，抑制SLC6A4和CGRP的表達，對硝酸甘油型大鼠偏頭痛癥狀有明顯的改善作用。結(jié)論 明確了養(yǎng)血清腦丸治療偏頭痛的潛在成分、靶點和通路，其作用機制可能與升高5-HT水平和5-HT1B蛋白表達、抑制SLC6A4和降鈣素基因相關肽（CGRP）表達有關，為深入開展其作用機制的研究提供了科學依據(jù)和參考。

Objective To explore the potential mechanism of Yangxue Qingnao Pills in treatment of migraine based on network pharmacology and molecular docking and to conduct its experimental verification. Methods TCMSP and Swiss Target Prediction databases were used to screen the active components and targets of Yangxue Qingnao Pills. Genes related to the occurrence and development of migraine were searched through databases of NCBI GENE, OMIM, CTD, and DisGeNET. The potential targets of treatment were obtained by taking the intersection of the two above. STRING database was used for establishing protein-protein interaction (PPI) networks and key targets were selected by Cytoscape 3.6.0. GO and KEGG pathways involved in the targets were analyzed by DAVID database. "Yangxue Qingnao Pills-herbs-active components-migraine-targets-pathways" network was constructed and key components were screened by Cytoscape 3.6.0, AutoDock software was used to dock the molecules of the key components with the key targets. The migraine rat model induced by nitroglycerin was used to verify key nodes in the results of network pharmacology. Results 140 active components and 279 targets of Yangxue Qingnao Pills were screened. 53 targets were identified for the intersection between Yangxue Qingnao Pills and migraine. The key targets of Yangxue Qingnao Pills in treatment of migraine were IL-6, SLC6A4, TNF, VEGFA, NOS3, etc. The key components were isocorypalmine, quercetin, (S)-scoulerine, bulbocapnine, kaempferol, etc. Molecular docking showed a good binding ability of key components and key target. The enrichment analysis of KEGG pathway showed that Yangxue Qingnao Pills treatment for migraine involved multiple pathways, including neuroactive ligand-receptor interaction, serotonergic synapse, calcium signaling pathway, cAMP signaling pathway, TNF signaling pathway, etc. The results of animal experiments showed that Yangxue Qingnao Pills could inhibit NO, IL-6, TNF-α, VEGF, SLC6A4, and CGRP in serum or brain tissue of migraine rats and increase of 5-HT and 5-HT1B level in brain tissue, significantly improve the symptoms of migraine rats. Conclusion This study reveals the potential active components, key targets and related pathways of Yangxue Qingnao Pills in treatment of migraine, the mechanism maybe related to increase of the level of 5-HT and the 5-HT1B protein expression, inhibition of SLC6A4 and CGRP expression, which provides a basis for further experiments.

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山西省教育廳高?？萍紕?chuàng)新計劃項目（2020L0227）；山西省運城市中心醫(yī)院院級項目（YJ2022107）