目的 旨在通過(guò)網(wǎng)絡(luò)藥理學(xué)探討姜黃素對(duì)肝臟缺血再灌注損傷（ HIRI）的影響。方法 采集姜黃素的化學(xué)結(jié)構(gòu)，并利用SwissTargetPrediction、PharmMapper等多個(gè)數(shù)據(jù)庫(kù)確定潛在的靶點(diǎn)。使用UniProt數(shù)據(jù)庫(kù)進(jìn)行數(shù)據(jù)轉(zhuǎn)換。從GEO數(shù)據(jù)庫(kù)（ GSE151648）中提取有關(guān)HIRI的信息。使用R軟件包DESeq2進(jìn)行差異基因表達(dá)分析尋找潛在的HIRI靶點(diǎn)。進(jìn)行加權(quán)基因共表達(dá)網(wǎng)絡(luò)分析（ WGCNA）確定交集靶點(diǎn)，并使用STRING平臺(tái)構(gòu)建蛋白質(zhì)-蛋白質(zhì)相互作用網(wǎng)絡(luò)（PPI）模型。通過(guò)基因本體（ GO）和京都基因與基因組百科全書(shū)（ KEGG）富集分析，結(jié)合機(jī)器學(xué)習(xí)進(jìn)一步篩選出關(guān)鍵基因，并利用AutodockTools和其他軟件完成核心分子的對(duì)接模擬。在此基礎(chǔ)上對(duì)小鼠進(jìn)行的體內(nèi)實(shí)驗(yàn)驗(yàn)證這些關(guān)鍵基因。結(jié)果 WGCNA分析確定了25個(gè)重疊的目標(biāo)，機(jī)器學(xué)習(xí)確定了5個(gè)與HIRI相關(guān)的關(guān)鍵基因。富集分析結(jié)果表明姜黃素和生物學(xué)過(guò)程如癌癥、細(xì)胞凋亡和轉(zhuǎn)錄核因子κB（ NF-κB）信號(hào)通路之間可能存在聯(lián)系。動(dòng)物實(shí)驗(yàn)驗(yàn)證組織染色切片與血清肝功能指標(biāo)，并進(jìn)一步驗(yàn)證關(guān)鍵基因的表達(dá)，從而驗(yàn)證姜黃素可以減輕HIRI損傷。結(jié)論 姜黃素可以通過(guò)下調(diào)促炎細(xì)胞因子和細(xì)胞周期蛋白水平來(lái)改善炎癥反應(yīng)與細(xì)胞凋亡，進(jìn)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

國(guó)家自然科學(xué)基金（82260802）；桂林市科技計(jì)劃項(xiàng)目（20220139-6-2）