目的 基于生物信息學(xué)分析右美托咪定治療腦缺血再灌注損傷的作用機(jī)制，結(jié)合分子對接和基因表達(dá)綜合庫（GEO）芯片驗(yàn)證明確核心基因。方法 采用PubChem和GeneCards篩選右美托咪定和腦缺血再灌注損傷交集靶點(diǎn)，建立蛋白相互作用（PPI）網(wǎng)絡(luò)確定Hub基因，進(jìn)行基因本體（GO）和京都基因與基因組百科全書（KEGG）富集分析，最終采用分子對接和GEO芯片數(shù)據(jù)驗(yàn)證Hub基因。結(jié)果 右美托咪定和腦缺血再灌注損傷有43個(gè)交集靶點(diǎn)，PPI篩選得到41個(gè)節(jié)點(diǎn)和103條邊的拓?fù)渚W(wǎng)絡(luò)，Hub基因?yàn)?-羥色胺受體2A（HTR2A）、阿片受體mu 1（OPRM1）、多巴胺受體D2（DRD2）、溶質(zhì)載體家族6成員4（SLC6A4）、谷氨酸代謝型受體5（GRM5）、細(xì)胞色素P450家族2亞家族C成員19（CYP2C19）、溶質(zhì)載體家族6成員3（SLC6A3）、核受體亞家族3C組成員1（NR3C1）、糖原合成酶激酶3β（GSK3β）。GO和KEGG分析顯示右美托咪定干預(yù)腦缺血再灌注損傷涉及254種生物學(xué)功能和58條信號(hào)通路。分子對接驗(yàn)證Hub基因均具有良好的親和力，GSE23160芯片驗(yàn)證預(yù)測DRD2、GSK3β和NR3C1具有差異性（P＜0.05）。結(jié)論 基于網(wǎng)絡(luò)藥理學(xué)及分子對接和基因芯片驗(yàn)證了右美托咪定通過多靶點(diǎn)、多生物學(xué)功能、多通路干預(yù)腦缺血再灌注損傷，并驗(yàn)證DRD2、GSK3β、NR3C1可能是核心基因，預(yù)測關(guān)鍵診斷基因和潛在治療基因，為進(jìn)一步研究奠定堅(jiān)實(shí)基礎(chǔ)。

Objective To analyze the mechanism of dexmedetomidine in treatment of cerebral ischemia-reperfusion injury based on bioinformatics, and to identify the hub genes by molecular docking and gene expression omnibus (GEO) chip verification. Methods PubChem and GeneCards were used to screen the intersection targets of dexmedetomidine and cerebral ischemia-reperfusion injury, establish a PPI network to determine hub genes, and perform GO and KEGG enrichment analysis. Finally, the Hub genes were verified by molecular docking and GEO chip data. Results There were 43 intersection targets between dexmedetomidine and cerebral ischemia-reperfusion injury. PPI screening obtained a topological network with 41 nodes and 103 edges, and the Hub genes were HTR2A, OPRM1, DRD2, SLC6A4, GRM5, CYP2C19, SLC6A3, NR3C1, and GSK3β. GO and KEGG analysis showed that dexmedetomidine intervention of cerebral ischemia-reperfusion injury involved 254 biological functions and 58 signaling pathways. Molecular docking verified that the hub genes had good affinity, and GSE23160 chip verified that DRD2, GSK3β, and NR3C1 were different (P < 0.05). Conclusions Based on network pharmacology, molecular docking, and gene chip, this study found that dexmedetomidine intervention of cerebral ischemia-reperfusion injury through multi-targets, multi-biological functions and multi-pathways, verified that DRD2, GSK3β, and NR3C1 may be the hub genes, predicted key diagnostic genes and potential therapeutic genes, and laid a solid foundation for further research.

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貴州省衛(wèi)生健康委科學(xué)技術(shù)基金資助項(xiàng)目（gzwjkj2020-1-110）