Xu Jiatong, Li Jiaying, Li Yan, Shi Xiaoxiao, Zhu Huadong, Chen Limeng
Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China.
Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China.
Biomolecules. 2023 Aug 30;13(9):1329. doi: 10.3390/biom13091329.
Sepsis-associated acute kidney injury (SA-AKI) is a severe and life-threatening condition with high morbidity and mortality among emergency patients, and it poses a significant risk of chronic renal failure. Clinical treatments for SA-AKI remain reactive and non-specific, lacking effective diagnostic biomarkers or treatment targets. In this study, we established an SA-AKI mouse model using lipopolysaccharide (LPS) and performed proteomics and metabolomics analyses. A variety of bioinformatic analyses, including gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), protein and protein interactions (PPI), and MetaboAnalyst analysis, were conducted to investigate the key molecules of SA-AKI. Integrated proteomics and metabolomics analysis revealed that sepsis led to impaired renal mitochondrial function and metabolic disorders. Immune-related pathways were found to be activated in kidneys upon septic infection. The catabolic products of polyamines accumulated in septic kidneys. Overall, our integrated analysis provides a multidimensional understanding of SA-AKI and identifies potential pathways for this condition.
脓毒症相关性急性肾损伤（SA-AKI）是一种严重且危及生命的疾病，在急诊患者中发病率和死亡率很高，并且它会带来慢性肾衰竭的重大风险。SA-AKI的临床治疗仍然是被动且非特异性的，缺乏有效的诊断生物标志物或治疗靶点。在本研究中，我们使用脂多糖（LPS）建立了SA-AKI小鼠模型，并进行了蛋白质组学和代谢组学分析。进行了多种生物信息学分析，包括基因集富集分析（GSEA）、加权基因共表达网络分析（WGCNA）、蛋白质与蛋白质相互作用（PPI）以及MetaboAnalyst分析，以研究SA-AKI的关键分子。蛋白质组学和代谢组学的综合分析表明，脓毒症导致肾线粒体功能受损和代谢紊乱。发现在脓毒症感染时肾脏中的免疫相关途径被激活。多胺的分解代谢产物在脓毒症肾脏中积累。总体而言，我们的综合分析提供了对SA-AKI的多维度理解，并确定了这种疾病的潜在途径。
