内科

目的利用生物信息学筛选脓毒症相关性急性肾损伤（SA-AKI）的关键基因，并探讨其潜在的调控机制。方法从GEO数据库获取人SA‑AKI转录组数据集GSE139061（包含39例SA-AKI患者肾活检样本和9例正常对照肾组织样本），采用R语言limma包筛选SA-AKI患者肾组织与正常对照间的差异表达基因（DEGs）。使用DAVID在线数据库对筛选所得DEGs进行基因本体论（GO）分析及京都基因与基因组百科全书（KEGG）通路分析。使用STRING在线数据库构建蛋白质-蛋白质相互作用（PPI）网络，并采用CytoNCA、MCODE插件筛选SA-AKI关键基因。结果共筛选出227个DEGs，其中202个基因表达上调、25个基因表达下调。GO分析显示DEGs主要富集于RNA加工、内皮细胞增殖正调控及纤维蛋白溶解正调控等生物学过程；KEGG通路分析显示DEGs主要富集于剪接体途径。通过PPI网络拓扑分析与MCODE功能模块挖掘，最终筛选出4个关键基因：纤溶酶原（PLG）、胰岛素样生长因子2（IGF2）、表皮生长因子（EGF）及TEK受体酪氨酸激酶（TEK）。结论 PLG、IGF2、EGF、TEK可能为SA-AKI的关键基因，通过调控纤溶稳态、肾小管修复、炎症反应及内皮屏障功能参与SA-AKI的病理进程；剪接体途径可能作为转录后水平的上游调控环节，与上述关键基因协同参与SA-AKI的发生发展，但其具体机制尚需进一步实验验证。

Objective To screen hub genes of sepsis-associated acute kidney injury (SA-AKI) by bioinformatics approaches and explore their potential regulatory mechanisms. Methods The human SA-AKI transcriptome dataset GSE139061, which contained renal biopsy samples from 39 SA-AKI patients and 9 normal control kidney tissue samples, was obtained from the GEO database. The limma package of R software was used to screen differentially expressed genes (DEGs) between kidney tissues of SA-AKI patients and normal controls. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the DEGs obtained by screening were performed by the DAVID online database. A protein-protein interaction (PPI) network was constructed via the STRING online database, and the CytoNCA and MCODE plugins were applied to screen hub genes for SA-AKI. Results A total of 227 DEGs were screened out, including 202 up-regulated genes and 25 down-regulated genes. GO analysis revealed that the DEGs were mainly enriched in biological processes such as RNA processing, positive regulation of endothelial cell proliferation, and positive regulation of fibrinolysis; KEGG pathway analysis indicated that the DEGs were primarily enriched in the spliceosome pathway. Four hub genes, plasminogen (PLG), insulin-like growth factor 2 (IGF2), epidermal growth factor (EGF), and TEK receptor tyrosine kinase (TEK), were finally identified through topological analysis of the PPI network and mining of functional modules by MCODE. Conclusion PLG, IGF2, EGF, and TEK may serve as hub genes of SA-AKI and participate in the pathological progression of SA-AKI by regulating fibrinolytic homeostasis, renal tubular repair, inflammatory response, and endothelial-barrier function. The spliceosome pathway may act as an upstream post-transcriptional regulatory link and cooperate with the above-mentioned hub genes in the genesis and progression of SA-AKI. However, further experimental validation is required to elucidate its exact mechanisms.

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