目的 基于生物信息數(shù)據(jù)庫平臺(tái)，采用網(wǎng)絡(luò)藥理學(xué)方法及分子對(duì)接技術(shù)研究牡荊苷通過鐵死亡途徑改善心肌缺血再灌注損傷的分子機(jī)制。方法 利用多個(gè)數(shù)據(jù)庫對(duì)牡荊苷的潛在靶點(diǎn)和心肌缺血再灌注損傷的相關(guān)靶點(diǎn)進(jìn)行篩選，取交集后構(gòu)建蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)并篩選核心靶點(diǎn)，對(duì)交集靶點(diǎn)進(jìn)行基因本體（GO）功能、京都基因與基因組百科全書（KEGG）通路富集分析，構(gòu)建“牡荊苷–靶點(diǎn)–通路”網(wǎng)絡(luò)并篩選關(guān)鍵核心靶點(diǎn)和通路。進(jìn)一步對(duì)牡荊苷潛在靶點(diǎn)、鐵死亡相關(guān)靶點(diǎn)、心肌缺血再灌注損傷相關(guān)靶點(diǎn)取交集，并篩選牡荊苷–鐵死亡–心肌缺血再灌注損傷相關(guān)的關(guān)鍵核心靶點(diǎn)。利用分子對(duì)接研究牡荊苷與各關(guān)鍵核心靶點(diǎn)間的結(jié)合機(jī)制。結(jié)果 牡荊苷與心肌缺血再灌注損傷的交集靶點(diǎn)共74個(gè)，篩選出腫瘤壞死因子（TNF）、淋巴細(xì)胞瘤-2（Bcl-2）、雌激素受體1（ESR1）等22個(gè)核心靶點(diǎn)，主要參與白細(xì)胞介素（IL）-17通路、脂質(zhì)和動(dòng)脈硬化通路等信號(hào)通路。分子對(duì)接結(jié)果表明牡荊苷與各關(guān)鍵核心靶點(diǎn)主要以氫鍵、范德華力、π-π堆積等作用力產(chǎn)生穩(wěn)定結(jié)合。結(jié)論 牡荊苷通過抑制炎癥反應(yīng)、細(xì)胞凋亡及調(diào)控鐵穩(wěn)態(tài)平衡和氧化應(yīng)激限制鐵死亡等多種生理過程的協(xié)同作用來達(dá)到改善心肌缺血再灌注損傷的效果。

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

國家重點(diǎn)研發(fā)計(jì)劃項(xiàng)目（2022YFD2200602）