摘要
目的基于蛋白组学鉴定感染性休克合并急性肾损伤(acute kidney injury,AKI)的早期生物学标志物。方法纳入2020年3月至2022年3月本院ICU收治且诊断为感染性休克的100例患者,其中42例合并AKI(AKI组),58例未发生AKI(NAKI组)。分别在患者感染性休克诊断后12 h和24 h收集尿液,并使用超高效液相色谱-四极杆飞行时间质谱(UPLC-QTOF/MS)进行代谢组学分析。通过比较聚类分析识别与损伤程度相关的全局蛋白质组模式,并确定感染性休克合并AKI的早期生物标志物。采用ELISA试剂盒分析尿液样品中中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)、几丁质酶样蛋白3(chitinase-like protein 3,Chil3)、S100钙结合蛋白A8(S100 calcium binding protein A8,S100A8)和铜蓝蛋白(ceruloplasmin,CP)含量。通过绘制受试者操作特征曲线(ROC)量化生物标志物的性能。结果与NAKI组相比,AKI组患者SCr、乳酸和全因死亡率显著增加(P<0.05),eGFR显著降低(P<0.001)。代谢组学分析显示,AKI患者中与细胞外基质和急性期反应相关的蛋白质在感染性休克诊断后增加,与离子、氨基酸和代谢物排泄相关的蛋白质以及与线粒体相关的蛋白质减少。全局蛋白质组模式分析显示,NGAL、Chil3、S100A8和CP为感染性休克合并AKI的早期生物学标志物。ELISA法验证结果显示,感染性休克合并AKI患者的NGAL、Chil3、S100A8和CP显著高于NAKI患者(P<0.05)。相关性分析显示,NGAL、Chil3、S100A8和CP表达与SCr呈显著正相关(r=0.276、0.391、0.789、0.721,均P<0.001)。ROC分析显示,标志物组合对感染性休克合并AKI具有较大诊断性能,在12 h和24 h的AUC分别为0.901和0.958。结论基于蛋白组学鉴定的NGAL、Chil3、S100A8和CP可作为识别感染性休克合并AKI的早期生物学标志物。
Objective To identify the early biomarkers of acute kidney injury(AKI)in septic shock patients based on proteomics.Methods A total of 100 patients admitted to the ICU of our hospital with a diagnosis of septic shock between March 2020 and March 2022 were recruited,of whom 42 had concurrent AKI and 58 had no AKI(NAKI).Urine samples were collected from these patients in 12 and 24 h after diagnosis of septic shock.Metabolomic analysis was performed using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS).Comparative cluster analysis was used to identify the global proteomic patterns associated with injury severity,and then to identify the early biomarkers of septic shock combined with AKI.Urine samples were analyzed the contents of neutrophil gelatinase-associated lipocalin(NGAL),chitinase-like protein 3(Chil3),S100 calcium binding protein A8(S100 A8)and ceruloplasmin(CP)with ELISA kits.Biomarker performance was quantified by plotting receiver operating characteristic(ROC)curves.Results The AKI group had significantly higher SCr and lactate levels and increased all-cause mortality(P<0.05),and obviously lower eGFR than the NAKI group(P<0.001).Metabolomic analysis revealed that the levels of proteins associated with extracellular matrix and acute-phase responses were increased after diagnosis of septic shock,while the levels of proteins associated with excretion of ions,amino acids,and metabolites,and mitochondria-associated proteins were decreased in the AKI patients.Global proteome pattern analysis revealed that NGAL,Chil3,S100 A8 and CP were early biomarkers of septic shock complicated with AKI.The results of ELISA indicated that NGAL,Chil3,S100 A8 and CP in AKI patients with septic shock were significantly higher than those without AKI(P<0.05).Correlation analysis showed that the expression levels of NGAL,Chil3,S100 A8 and CP were positively correlated with SCr level(r=0.276,0.391,0.789,0.721,all P<0.001).ROC analysis suggested that the combination of these markers had greater diagnostic performance in diagnosing septic shock complicated with AKI,and the AUCs at 12 h and 24 h were 0.901 and 0.958,respectively.Conclusion NGAL,Chil3,S100 A8 and CP based on proteomics can be used as early biomarkers for identifying septic shock complicated with AKI.
作者
周艳红
周明明
李爱华
ZHOU Yanhong;ZHOU Mingming;LI Aihua(Department of Medical Insurance,Affiliated Cancer Hospital of Chongqing University,Chongqing,400030,China;Department of Critical Care Medicine,Affiliated Cancer Hospital of Chongqing University,Chongqing,400030,China;Department of Gastroenterology,Affiliated Cancer Hospital of Chongqing University,Chongqing,400030,China)
出处
《陆军军医大学学报》
CAS
CSCD
北大核心
2022年第21期2183-2191,共9页
Journal of Army Medical University
基金
重庆市科研机构绩效激励引导专项(cstc2020jxjl130017)
作者简介
通信作者:李爱华,E-mail:huahua062883@sohu.com
