目的 基于生物信息数据库平台，采用网络药理学方法及分子对接技术研究牡荆苷通过铁死亡途径改善心肌缺血再灌注损伤的分子机制。方法 利用多个数据库对牡荆苷的潜在靶点和心肌缺血再灌注损伤的相关靶点进行筛选，取交集后构建蛋白质相互作用（PPI）网络并筛选核心靶点，对交集靶点进行基因本体（GO）功能、京都基因与基因组百科全书（KEGG）通路富集分析，构建“牡荆苷–靶点–通路”网络并筛选关键核心靶点和通路。进一步对牡荆苷潜在靶点、铁死亡相关靶点、心肌缺血再灌注损伤相关靶点取交集，并筛选牡荆苷–铁死亡–心肌缺血再灌注损伤相关的关键核心靶点。利用分子对接研究牡荆苷与各关键核心靶点间的结合机制。结果 牡荆苷与心肌缺血再灌注损伤的交集靶点共74个，筛选出肿瘤坏死因子（TNF）、淋巴细胞瘤-2（Bcl-2）、雌激素受体1（ESR1）等22个核心靶点，主要参与白细胞介素（IL）-17通路、脂质和动脉硬化通路等信号通路。分子对接结果表明牡荆苷与各关键核心靶点主要以氢键、范德华力、π-π堆积等作用力产生稳定结合。结论 牡荆苷通过抑制炎症反应、细胞凋亡及调控铁稳态平衡和氧化应激限制铁死亡等多种生理过程的协同作用来达到改善心肌缺血再灌注损伤的效果。

Objective To study the molecular mechanism of vitexin in improving myocardial ischemia reperfusion injury through iron death pathway based on the biological information database platform, network pharmacology, and molecular docking techniques. Methods To screen potential targets of vitexin and related targets of myocardial ischemia reperfusion injury by multiple databases. After intersection, PPI network was constructed and core targets were screened. GO function and KEGG pathway enrichment analysis were performed on the intersection targets. Construct the “vitexin–target–pathway” network and screen the key core targets and pathways. Further, the intersection of potential targets of vitexin, iron death-related targets, and myocardial ischemia reperfusion injury related targets was selected, and the key core targets related to vitexin, iron death-myocardial ischemia reperfusion injury were screened. Molecular docking was used to study the binding mechanism between vitexin and key core targets. Results A total of 74 intersecting targets of vitexin and myocardial ischemia reperfusion injury were screened out. Among which, 22 core targets including tumor necrosis factor (TNF), lymphoblastoma-2 (Bcl-2) and estrogen receptor 1 (ESR1) were identified, these core targets participate extensively in signaling pathways related to lipid metabolism, atherosclerosis, and the IL-17 pathway. Molecular docking results indicated that vitexin could bind to the tested key targets through hydrogen bonds, van der Waals forces, π-π interactions, and other interactions. Conclusion Vitexin can ameliorate myocardial ischemiation reperfusion injury by inhibiting inflammatory response, apoptosis, regulating iron homeostasis and limiting iron death through oxidative stress.

R285

国家重点研发计划项目（2022YFD2200602）