Li Yiming, Long Junke, Chen Jiaquan, Zhang Jing, Qin Yi, Zhong Yanjun, Liu Fen, Peng Zhiyong
Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
Front Physiol. 2020 Mar 3;11:139. doi: 10.3389/fphys.2020.00139. eCollection 2020.
Acute kidney injury (AKI) is a frequent complication of sepsis and contributes to increased mortality. Discovery of reliable biomarkers could enable identification of individuals with high AKI risk as well as early AKI detection and AKI progression monitoring. However, the current methods are insensitive and non-specific. This study aimed to identify new biomarkers through label-free mass spectrometry (MS) analysis of a sepsis model induced by cecal ligation and puncture (CLP). Urine samples were collected from septic rats at 0, 3, 6, 12, 24, and 48 h. Protein isolated from urine was subjected to MS. Immunoregulatory biological processes, including immunoglobin production and wounding and defense responses, were upregulated at early time points. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses identified 77 significantly changed pathways. We further examined the consistently differentially expressed proteins to seek biomarkers that can be used for early diagnosis. Notably, the expression of PARK7 and CDH16 were changed in a continuous manner and related to the level of Scr in urine from patients. Therefore, PARK7 and CDH16 were confirmed to be novel biomarkers after validation in sepsis human patients. In summary, our study analyzed the proteomics of AKI at multiple time points, elucidated the related biological processes, and identified novel biomarkers for early diagnosis of sepsis-induced AKI, and our findings provide a theoretical basis for further research on the molecular mechanisms.
急性肾损伤（AKI）是脓毒症常见的并发症，会导致死亡率升高。发现可靠的生物标志物有助于识别高AKI风险个体，以及早期检测AKI和监测AKI进展。然而，目前的方法不敏感且缺乏特异性。本研究旨在通过对盲肠结扎穿孔（CLP）诱导的脓毒症模型进行无标记质谱（MS）分析来识别新的生物标志物。在0、3、6、12、24和48小时从脓毒症大鼠收集尿液样本。从尿液中分离的蛋白质进行质谱分析。包括免疫球蛋白产生以及创伤和防御反应在内的免疫调节生物学过程在早期时间点上调。京都基因与基因组百科全书（KEGG）通路富集分析确定了77条显著变化的通路。我们进一步检查持续差异表达的蛋白质，以寻找可用于早期诊断的生物标志物。值得注意的是，PARK7和CDH16的表达持续变化，且与患者尿液中Scr水平相关。因此，在脓毒症人类患者中验证后，PARK7和CDH16被确认为新的生物标志物。总之，我们的研究在多个时间点分析了AKI的蛋白质组学，阐明了相关生物学过程，识别了脓毒症诱导的AKI早期诊断的新生物标志物，我们的发现为进一步研究分子机制提供了理论基础。
