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血清外泌体低氧诱导因子-1 ɑ(HIF-1ɑ)在细菌性腹膜炎潜在循环生物标志物中的应用。

Application of serum exosomal hypoxia-inducible factor-1 alpha (HIF-1α) as potential circulating biomarker for bacterial peritonitis.

机构信息

State Key Laboratories for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China.

School of Materials Science and Engineering, Tsinghua University, Shaw Technical Science Building, Beijing, China.

出版信息

Bioengineered. 2022 Feb;13(2):1975-1987. doi: 10.1080/21655979.2021.2006866.

DOI:10.1080/21655979.2021.2006866
PMID:34898382
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8973742/
Abstract

Bacterial peritonitis is a severe disease that diagnosis remains challenging for clinicians. Measuring biomarkers might be a rapid diagnostic method. The objective of this study was to analyze and evaluate the dynamic changes in HIF-1α concentration in serum exosomes during bacterial peritonitis. The pre-clinical application value of serum exosomal HIF-1α was evaluated via imipenem and cilastatin sodium (ICS) intervention in the bacterial peritonitis model. The new colorimetric method to quantitate dynamic expression changes of HIF-1α in serum exosomes during bacterial peritonitis was established by our team via using the gold seed-coated with aptamer-functionalized Au @ Au core-shell peroxidase mimic. The typical inflammatory cytokines of bacterial peritonitis were also measured. Following intramuscular administration with ICS, Xtreme imaging system was used to visualize abdominal infection extent. Meanwhile, HIF-1α concentration in rat serum exosomes and pro-inflammatory factors levels in serum were detected. The serum typical inflammatory cytokines levels were elevated in GFP-labeled induced bacterial peritonitis. The serum exosomal HIF-1α levels clearly increased at 12 h, reached the peak during 24-48 h, and then gradually decreased at 72 h. Following intramuscular administration with ICS, the abdominal infection extent, HIF-1α concentration in serum exosomes, and the serum pro-inflammatory factors levels were reduced at 24 h in GFP-labeled induced bacterial peritonitis model. The serum exosomal HIF-1α can be used as a biomarker in the early stage of bacterial peritonitis, which might provide the basic research in the pre-clinical for further predicting and monitoring the pathological process of bacterial peritonitis.

摘要

细菌性腹膜炎是一种严重的疾病,临床医生的诊断仍然具有挑战性。测量生物标志物可能是一种快速诊断方法。本研究的目的是分析和评估血清外泌体中 HIF-1α 浓度在细菌性腹膜炎期间的动态变化。通过亚胺培南和西司他丁钠 (ICS) 干预细菌性腹膜炎模型,评估了血清外泌体 HIF-1α 的临床前应用价值。我们团队通过使用金种子包被适配体功能化的 Au@Au 核壳过氧化物酶模拟物,建立了一种新的比色法定量分析细菌性腹膜炎期间血清外泌体中 HIF-1α 动态表达变化的方法。还测量了细菌性腹膜炎的典型炎症细胞因子。在 ICS 肌肉注射后,使用 Xtreme 成像系统可视化腹部感染程度。同时,检测大鼠血清外泌体中 HIF-1α 浓度和血清中促炎因子水平。在 GFP 标记的 LPS 诱导的细菌性腹膜炎中,血清中典型炎症细胞因子水平升高。血清外泌体 HIF-1α 水平在 12 小时明显升高,在 24-48 小时达到峰值,然后在 72 小时逐渐下降。在 GFP 标记的 LPS 诱导的细菌性腹膜炎模型中,ICS 肌肉注射后 24 小时,腹部感染程度、血清外泌体 HIF-1α 浓度和血清促炎因子水平降低。血清外泌体 HIF-1α 可作为细菌性腹膜炎早期的生物标志物,为进一步预测和监测细菌性腹膜炎的病理过程提供临床前基础研究。

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