目的 基于網(wǎng)絡(luò)藥理學(xué)、分子對(duì)接技術(shù)和體外實(shí)驗(yàn)驗(yàn)證探究五味子丙素抗膠質(zhì)瘤的作用及其機(jī)制。方法 通過TCMSP等數(shù)據(jù)庫篩選五味子丙素相關(guān)靶點(diǎn)，借助GeneCards等數(shù)據(jù)庫收集膠質(zhì)瘤相關(guān)靶點(diǎn)，得到五味子丙素與膠質(zhì)瘤的交集靶點(diǎn)并繪制韋恩圖，用STRING數(shù)據(jù)庫構(gòu)建PPI網(wǎng)絡(luò)，并利用Cytoscape軟件篩選出核心交集靶點(diǎn)。利用DAVID數(shù)據(jù)庫對(duì)交集靶點(diǎn)進(jìn)行基因本體論（GO）和京都基因和基因百科全書（KEGG）富集分析，用AutoDock軟件通過分子對(duì)接驗(yàn)證五味子丙素與核心交集靶點(diǎn)的結(jié)合能力，并運(yùn)用PyMol軟件可視化分析。體外實(shí)驗(yàn)采用五味子丙素（25、50、100 μmol/L）處理人膠質(zhì)瘤U251細(xì)胞，應(yīng)用CCK-8、劃痕實(shí)驗(yàn)、Western Blotting等方法檢測(cè)五味子丙素對(duì)細(xì)胞增殖、遷移及蛋白表達(dá)的影響。結(jié)果 共篩選出藥物靶點(diǎn)98個(gè)，疾病靶點(diǎn)3 230個(gè)，藥物與疾病交集靶點(diǎn)63個(gè)，核心靶點(diǎn)為蛋白激酶B1（Akt1）、表皮生長(zhǎng)因子受體（EGFR）、肉瘤病毒蛋白（SRC）、哺乳動(dòng)物雷帕霉素靶蛋白（mTOR）、表皮生長(zhǎng)因子受體2（ERBB2）、磷酸肌醇-3-激酶催化亞基α（PIK3CA）等。KEGG通路142條，主要包括磷脂酰肌醇-3激酶（PI3K）/Akt、Rap1和低氧誘導(dǎo)因子-1（HIF-1）信號(hào)通路等。體外研究發(fā)現(xiàn)，與對(duì)照組相比，五味子丙素50、100 μmol/L能抑制人膠質(zhì)瘤U251細(xì)胞的增殖和遷移，且五味子丙素25、50、100 μmol/L均能顯著降低PI3K/Akt通路相關(guān)蛋白p-Akt和p-ERK1/2蛋白的表達(dá)（P＜0.05、0.01、0.001）。結(jié)論 五味子丙素可能通過PI3K/Akt信號(hào)通路抑制人膠質(zhì)瘤U251細(xì)胞的增殖和遷移。

Objective To investigate the anti-glioma effect of schisandrin C, and its mechanism based on network pharmacology, molecular docking technology and in vitro experimental validation. Methods Schisandrin C related targets were screened through databases such as TCMSP, and glioma related targets were collected using databases like GeneCards. The intersection targets between schisandrin C and glioma were identified and a Venn diagram was drawn. PPI network was constructed using the STRING database, and core intersection targets were screened using the Cytoscape software. GO and KEGG enrichment analyses of the intersecting targets were performed using the DAVID database. The binding ability of schisandrin C to the core intersection targets was verified by molecular docking using AutoDock software, and visualised and analysed using PyMol software. Finally, human glioma U251 cells were treated with schisandrin C (25, 50, and 100 μmol/L), and CCK-8, scratch assay and Western Blotting were applied to detect the effects of different concentrations of schisandrin C on cell proliferation, migration and protein expression. Results A total of 98 drug targets, 3 230 disease targets, and 63 drug-disease intersection targets were screened, and the core targets were Akt1, EGFR, SRC, mTOR, ERBB2, PIK3CA, etc. 142 KEGG pathways were identified, which mainly included PI3K/Akt, Rap1, and HIF-1 signalling pathways. In vitro studies found that compared with the control group, schisandrin C 50 and 100 μmol/L inhibited the proliferation and migration of human glioma U251 cells, and low, schisandrin C 25, 50, and 100 μmol/L groupsignificantly reduced the expression of PI3K/Akt pathway-related proteins (P < 0.05, 0.01, 0.001), p-Akt and p-ERK1/2 proteins. Conclusion Schisandrin C may inhibit the proliferation and migration of human glioma U251 cells through the PI3K/Akt signalling pathway.

R285.5

黑龍江省中醫(yī)藥管理局項(xiàng)目（ZHY2023-115）；齊齊哈爾市科技計(jì)劃聯(lián)合引導(dǎo)項(xiàng)目（LSFGG-2022049）；齊齊哈爾醫(yī)學(xué)科學(xué)院臨床科研基金項(xiàng)目（QMSI2019L-24）