目的 基于網絡藥理學、分子對接技術和體外實驗驗證探究五味子丙素抗膠質瘤的作用及其機制。方法 通過TCMSP等數據庫篩選五味子丙素相關靶點，借助GeneCards等數據庫收集膠質瘤相關靶點，得到五味子丙素與膠質瘤的交集靶點并繪制韋恩圖，用STRING數據庫構建PPI網絡，并利用Cytoscape軟件篩選出核心交集靶點。利用DAVID數據庫對交集靶點進行基因本體論（GO）和京都基因和基因百科全書（KEGG）富集分析，用AutoDock軟件通過分子對接驗證五味子丙素與核心交集靶點的結合能力，并運用PyMol軟件可視化分析。體外實驗采用五味子丙素（25、50、100 μmol/L）處理人膠質瘤U251細胞，應用CCK-8、劃痕實驗、Western Blotting等方法檢測五味子丙素對細胞增殖、遷移及蛋白表達的影響。結果 共篩選出藥物靶點98個，疾病靶點3 230個，藥物與疾病交集靶點63個，核心靶點為蛋白激酶B1（Akt1）、表皮生長因子受體（EGFR）、肉瘤病毒蛋白（SRC）、哺乳動物雷帕霉素靶蛋白（mTOR）、表皮生長因子受體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和低氧誘導因子-1（HIF-1）信號通路等。體外研究發(fā)現，與對照組相比，五味子丙素50、100 μmol/L能抑制人膠質瘤U251細胞的增殖和遷移，且五味子丙素25、50、100 μmol/L均能顯著降低PI3K/Akt通路相關蛋白p-Akt和p-ERK1/2蛋白的表達（P＜0.05、0.01、0.001）。結論 五味子丙素可能通過PI3K/Akt信號通路抑制人膠質瘤U251細胞的增殖和遷移。

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)藥管理局項目（ZHY2023-115）；齊齊哈爾市科技計劃聯合引導項目（LSFGG-2022049）；齊齊哈爾醫(yī)學科學院臨床科研基金項目（QMSI2019L-24）