目的 整合网络药理学、分子对接与体外实验，系统阐明姜黄素治疗脑梗死的多靶点机制。方法 运用网络药理学筛选姜黄素与脑梗死的共同靶点，构建相关网络并开展基因本体（GO）功能富集分析和京都基因与基因组百科全书（KEGG）富集分析，通过分子对接验证核心靶点结合活性；以N2a细胞构建氧糖剥夺/复氧（OGD/R）模型，设置对照组、模型组及姜黄素组，采用CCK-8法、Annexin V-FITC/PI双染、流式细胞术分别检测细胞活力、凋亡率及ROS阳性率，通过RT-qPCR检测E1A结合蛋白p300（EP300）、信号转导及转录激活蛋白3（STAT3）、组蛋白去乙酰化酶1（HDAC1）的mRNA表达水平。结果 姜黄素与脑梗死共有145个交集靶点，PPI网络筛选出STAT3、EP300、HDAC1等6个核心靶点。分子对接显示姜黄素与EP300结合能最低。与模型组比较，姜黄素（15.0、30.0 μmol/L）组显著改善N2a细胞活力（P＜0.001）；姜黄素30.0 μmol/L组凋亡率及ROS水平均显著降低（P＜0.01、0.001），EP300、STAT3、HDAC1 mRNA表达显著降低（P＜0.05）。结论 姜黄素可能通过下调EP300、STAT3、HDAC1的表达，减轻氧化应激、炎症与神经元凋亡，发挥神经保护作用。

Objective To systematically elucidate the multi-target mechanism of curcumin in treatment of cerebral infarction by integrating network pharmacology, molecular docking, and in vitro experiments. Methods To screen common targets of curcumin and cerebral infarction by network pharmacology, construct relevant networks, and perform GO and KEGG enrichment analyses. Molecular docking was conducted to validate the binding activity of core targets. The N2a cells were used to construct the OGD/R model. A control group, model group and curcumin group were set up. The cell viability, apoptosis rate and ROS positive rate were detected by CCK-8 method, Annexin V-FITC/PI double staining and flow cytometry, respectively. The mRNA expression levels of EP300, STAT3, and HDAC1 were detected by RT-qPCR. Results A total of 145 intersection targets between curcumin and cerebral infarction were identified. PPI network analysis screened out 6 core targets including STAT3, EP300, and HDAC1. Molecular docking revealed that curcumin had the lowest binding energy with EP300. Compared with the model group, curcumin (15 and 30 μmol/L) groups significantly improved N2a cell viability (P < 0.001). Curcumin 30 μmol/L group showed significantly reduced apoptosis rate and ROS levels (P < 0.01, 0.001), as well as significantly decreased mRNA expression of EP300, STAT3, and HDAC1 (P < 0.05). Conclusion Curcumin may exert neuroprotective effects by downregulating the expression of EP300, STAT3, and HDAC1, thereby alleviating oxidative stress, inflammation, and neuronal apoptosis.

R286.1

黑龙江省中医药科研项目（ZHY2023-114）