通过生物信息学方法及动物实验寻找并验证与内质网应激相关的急性肾损伤(AKI)共表达关键基因，探索分析这些基因在AKI的发生和发展中的作用。

本文选取了基因表达综合数据库中的GSE30718数据集，从中筛选与内质网应激相关的差异基因。采用差异分析、分组比较、蛋白相互作用网络分析、相关性分析、受试者工作特征(ROC)曲线分析、基因本体和京都基因与基因组百科全书富集分析等方法，对内质网应激的特征基因的表达特征进行分析。进一步使用了对侧肾切除＋单侧肾缺血再灌注损伤小鼠模型进行实验验证，通过在不同时间点(1 d、3 d、7 d和14 d)采集模型小鼠的肾脏组织进行实时荧光定量核酸扩增检测系统(qPCR)实验，对相关基因的表达特征进行分析。

发现11个与内质网应激相关的AKI共表达基因蛋白，包括FOS、VMP1、CEL、HSP90B1、TIMP1、FAS、RDH12、RALYL、PCK2、LCN2和PTX3。通过蛋白相互作用网络分析，找出了与上述基因密切相关的20个节点基因；相关性分析提示除HSP90B1与FOS之间无明显相关性外，其他内质网应激相关差异基因两两之间均密切相关；ROC曲线分析提示上述11个基因的ROC曲线下面积均>0.70；基因本体和京都基因与基因组百科全书富集分析提示，FOS、HSP90B1和LCN2参与了IL-17信号通路，通过影响细胞的增殖、内质网功能、及组装蛋白的分泌，从而影响AKI进展。在对侧肾切除＋单侧肾缺血再灌注损伤小鼠模型的qPCR实验中，Timp1、Lcn2基因表达早期显著增高，而Fos仅在14 d时显著增加；Hsp90b1、Ptx3、Rdh12等基因表达呈总体下降趋势，且均在早期出现了显著的下降。Western印迹结果提示Lcn2、Timp1、c-Fos随AKI的进展呈增多趋势。

本研究发现了11个内质网应激相关的AKI共表达基因，可能通过IL-17信号通路影响细胞的增殖、内质网功能、及组装蛋白的分泌进程，参与调节内质网应激，进而影响AKI的进展。内质网应激相关差异基因与炎症反应、细胞凋亡和细胞周期调控等功能具有一定的相关性，且可能对AKI具有较好的诊断价值，其中4个基因在动物实验中得到了关键性验证，为后续探索内质网应激影响AKI的机制研究提供新的靶点和思路。

To explore the key genes associated with both acute kidney injury (AKI) and endoplasmic reticulum (ER) stress through bioinformatic methods and animal experiments.

The gene expression omnibus (GEO) dataset GSE30718 was selected for this study, and differentially expressed genes (DEGs) related to ER stress were screened. Differential analysis, group comparison, protein-protein interaction (PPI) network analysis, correlation analysis, receiver operating characteristic (ROC) curve analysis, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to analyze the expression characteristics of ER stress-related genes. Furthermore, an experimental validation was conducted using a unilateral ischemia-reperfusion injury with contralateral nephrectomy (uIRIx) mouse model, and real-time fluorescence quantitative polymerase chain reaction (qPCR) experiments were performed on kidney tissues collected at different time points (1 d, 3 d, 7 d, and 14 d) to analyze the expression characteristics of the relevant genes.

Eleven ER stress-related genes co-expressed in AKI were discovered, including FOS, VMP1, CEL, HSP90B1, TIMP1, FAS, RDH12, RALYL, PCK2, LCN2, and PTX3. Through PPI network analysis, 20 node genes closely related to the above-mentioned genes were found. Correlation analysis suggested that all ER stress-related DEGs except for HSP90B1 and FOS were closely correlated with each other. ROC analysis suggested that the area under the curve for the above 11 genes was greater than 0.70. GO and KEGG enrichment analysis suggested that FOS, HSP90B1, and LCN2 were involved in the IL-17 signaling pathway, affecting cell proliferation, endoplasmic reticulum function, and assembly of secreted proteins, thereby influencing the progression of AKI. In the uIRIx model of animals, qPCR experiments showed that Timp1 and Lcn2 were significantly elevated early on, while Fos only significantly increased after 14 days. The expression of Hsp90b1, Ptx3, Rdh12, and other genes showed an overall downward trend with significant decreases early on. Western blot experiments suggested that Lcn2, Timp1, and c-Fos increased with the progression of AKI.

Eleven ER stress-related genes co-expressed in AKI were discovered that might affect the progression of AKI through the IL-17 signaling pathway, affecting cell proliferation, endoplasmic reticulum function, and assembly of secreted proteins. ER stress-related DEGs were also related to inflammation, cell apoptosis, and cell cycle regulation, and might have good diagnostic value for AKI. Four of these genes were critically validated in animals experiments, providing new targets and ideas for further exploration of the mechanisms by which ER stress may affect AKI.