感染性休克合并急性肾损伤的尿蛋白组学研究

周艳红; 周明明; 李爱华

doi:10.16016/j.2097-0927.202204150

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感染性休克合并急性肾损伤的尿蛋白组学研究

临床医学 | 更新时间：2026-01-09

- 感染性休克合并急性肾损伤的尿蛋白组学研究
- Urinary proteomics in septic shock complicated with acute kidney injury
- 陆军军医大学学报 2022年44卷第21期页码：2183-2191
- 作者机构：
  
  1.400030 重庆，重庆大学附属肿瘤医院：医保科
  2.400030 重庆，重庆大学附属肿瘤医院：重症医学科
  3.400030 重庆，重庆大学附属肿瘤医院：消化内科
- 作者简介：
  
  [李爱华，E-mail：huahua062883@sohu.comLI Aihua, E-mail: huahua062883@sohu.com
- 基金信息：
  
  重庆市科研机构绩效激励引导专项(cstc2020jxjl130017)
- DOI：10.16016/j.2097-0927.202204150
  中图分类号： R446.122;R631.4;R692.5
- 收稿：2022-04-20，
  
  修回：2022-07-13，
  
  纸质出版：2022-11-15
- 稿件说明：
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周艳红, 周明明, 李爱华. 感染性休克合并急性肾损伤的尿蛋白组学研究[J]. 陆军军医大学学报, 2022,44(21):2183-2191.

Yanhong ZHOU, Mingming ZHOU, Aihua LI. Urinary proteomics in septic shock complicated with acute kidney injury[J]. Journal of Army Medical University, 2022, 44(21): 2183-2191.
周艳红, 周明明, 李爱华. 感染性休克合并急性肾损伤的尿蛋白组学研究[J]. 陆军军医大学学报, 2022,44(21):2183-2191. DOI： 10.16016/j.2097-0927.202204150.

Yanhong ZHOU, Mingming ZHOU, Aihua LI. Urinary proteomics in septic shock complicated with acute kidney injury[J]. Journal of Army Medical University, 2022, 44(21): 2183-2191. DOI： 10.16016/j.2097-0927.202204150.

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(

＜0.05)，eGFR显著降低(

＜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(

＜0.05)。相关性分析显示，NGAL、Chil3、S100A8和CP表达与SCr呈显著正相关(

=0.276、0.391、0.789、0.721，均

＜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。

Abstract

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(S100A8) 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 (

0.05)

and obviously lower eGFR than the NAKI group(

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

S100A8 and CP were early biomarkers of septic shock complicated with AKI. The results of ELISA indicated that NGAL

Chil3

S100A8 and CP in AKI patients with septic shock were significantly higher than those without AKI(

0.05). Correlation analysis showed that the expression levels of NGAL

Chil3

S100A8 and CP were positively correlated with SCr level(

=0.276

0.391

0.789

0.721

all

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

S100A8 and CP based on proteomics can be used as early biomarkers for identifying septic shock complicated with AKI.

关键词

Keywords

references

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