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肾毒性抗生素治疗的脓毒症患者循环 microRNAs 的表达及 7 天时间进程。

Expression and 7-day time course of circulating microRNAs in septic patients treated with nephrotoxic antibiotic agents.

机构信息

Department of Internal Medicine and Cardiology, University Hospital Ostrava, 70852, Ostrava, Czech Republic.

Faculty of Medicine, University of Ostrava, 70300, Ostrava, Czech Republic.

出版信息

BMC Nephrol. 2022 Mar 19;23(1):111. doi: 10.1186/s12882-022-02726-6.

Abstract

BACKGROUND

Through regulation of signaling pathways, microRNAs (miRNAs) can be involved in sepsis and associated organ dysfunction. The aims of this study were to track the 7-day time course of blood miRNAs in patients with sepsis treated with vancomycin, gentamicin, or a non-nephrotoxic antibiotic and miRNA associations with neutrophil gelatinase-associated lipokalin (NGAL), creatinine, procalcitonin, interleukin-6, and acute kidney injury (AKI) stage.

METHODS

Of 46 adult patients, 7 were on vancomycin, 20 on gentamicin, and 19 on another antibiotic. Blood samples were collected on days 1, 4, and 7 of treatment, and miRNAs were identified using quantitative reverse transcription PCR.

RESULTS

The results showed no relationship between miRNA levels and biochemical variables on day 1. By day 7 of gentamicin treatment miR-15a-5p provided good discrimination between AKI and non-AKI (area under curve, 0.828). In patients taking vancomycin, miR-155-5p and miR-192-5p positively correlated with creatinine and NGAL values, and miR-192-5p and miR-423-5p positively correlated with procalcitonin and interleukin-6 in patients treated with a non-nephrotoxic antibiotic. In patients together we found positive correlation between miR-155-5p and miR-423-5p and all biochemical markers.

CONCLUSION

The results suggest that these four miRNAs may serve as diagnostic or therapeutic tool in sepsis, renal injury and nephrotoxic treatment.

TRIAL REGISTRATION

ClinicalTrials.gov , ID: NCT04991376 . Registered on 27 July 2021.

摘要

背景

通过调节信号通路,微小 RNA(miRNA)可参与脓毒症及其相关器官功能障碍。本研究的目的是追踪接受万古霉素、庆大霉素或非肾毒性抗生素治疗的脓毒症患者的血液 miRNA 7 天时间过程,以及 miRNA 与中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肌酐、降钙素原、白细胞介素-6 和急性肾损伤(AKI)分期的关系。

方法

在 46 名成年患者中,7 名接受万古霉素治疗,20 名接受庆大霉素治疗,19 名接受另一种抗生素治疗。在治疗的第 1、4 和 7 天采集血样,并使用定量逆转录 PCR 鉴定 miRNA。

结果

结果表明,miRNA 水平与第 1 天的生化变量之间没有关系。在庆大霉素治疗的第 7 天,miR-15a-5p 对 AKI 和非 AKI 有很好的区分能力(曲线下面积,0.828)。在接受万古霉素治疗的患者中,miR-155-5p 和 miR-192-5p 与肌酐和 NGAL 值呈正相关,而 miR-192-5p 和 miR-423-5p 与非肾毒性抗生素治疗的患者的降钙素原和白细胞介素-6 呈正相关。在所有患者中,我们发现 miR-155-5p 和 miR-423-5p 与所有生化标志物之间呈正相关。

结论

结果表明,这四种 miRNA 可能作为脓毒症、肾损伤和肾毒性治疗的诊断或治疗工具。

试验注册

ClinicalTrials.gov,ID:NCT04991376。于 2021 年 7 月 27 日注册。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0da0/8933949/fca9847406f8/12882_2022_2726_Fig1_HTML.jpg

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