目的 旨在通过网络药理学探讨姜黄素对肝脏缺血再灌注损伤（ HIRI）的影响。方法 采集姜黄素的化学结构，并利用SwissTargetPrediction、PharmMapper等多个数据库确定潜在的靶点。使用UniProt数据库进行数据转换。从GEO数据库（ GSE151648）中提取有关HIRI的信息。使用R软件包DESeq2进行差异基因表达分析寻找潜在的HIRI靶点。进行加权基因共表达网络分析（ WGCNA）确定交集靶点，并使用STRING平台构建蛋白质-蛋白质相互作用网络（PPI）模型。通过基因本体（ GO）和京都基因与基因组百科全书（ KEGG）富集分析，结合机器学习进一步筛选出关键基因，并利用AutodockTools和其他软件完成核心分子的对接模拟。在此基础上对小鼠进行的体内实验验证这些关键基因。结果 WGCNA分析确定了25个重叠的目标，机器学习确定了5个与HIRI相关的关键基因。富集分析结果表明姜黄素和生物学过程如癌症、细胞凋亡和转录核因子κB（ NF-κB）信号通路之间可能存在联系。动物实验验证组织染色切片与血清肝功能指标，并进一步验证关键基因的表达，从而验证姜黄素可以减轻HIRI损伤。结论 姜黄素可以通过下调促炎细胞因子和细胞周期蛋白水平来改善炎症反应与细胞凋亡，进而改善HIRI。

Objective To explore the effect of curcumin on liver ischemia-reperfusion injury through network pharmacology. Methods The chemical structure of curcumin was collected, and the potential targets were identified by using SwissTargetPrediction, PharmMapper and other databases. UniProt database was used for data conversion. Information about hepatic ischemia-reperfusion injury (HIRI) was extracted from GEO database (GSE151648). Differential gene expression analysis was carried out by using R software package DESeq2 to find potential HIRI targets. WGCNA analysis was carried out to determine the intersection targets, and the protein interaction network model was constructed using the STRING platform. Through the enrichment analysis of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), combined with machine learning, the key genes were further screened out, and the docking simulation of core molecules was completed by using AutodockTools and other software. On this basis, these key genes were verified by in vivo experiments on mice. Results WGCNA analysis identified 25 overlapping targets, and machine learning identified five key genes related to HIRI. The results of enrichment analysis showed that there may be a relationship between curcumin and biological processes such as cancer, apoptosis and NF-κB signaling pathway. Animal experiments verify tissue staining sections and serum liver function indexes, and further verify the expression of key genes, thus verifying that curcumin can alleviate the injury of HIRI. Conclusion Curcumin can improve inflammatory reaction and apoptosis by down-regulating the levels of pro-inflammatory cytokines and isopycycline, and then improve HIRI.

R285.5

国家自然科学基金（82260802）；桂林市科技计划项目（20220139-6-2）