神经元衍生细胞外小泡 miRNA 图谱可识别因手术镇静而使用氯胺酮后出现不良反应的儿童。

IF 6.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Clinical Pharmacology & Therapeutics Pub Date : 2024-08-20 DOI:10.1002/cpt.3420
Marianna Lucafò, Carlotta Bidoli, Martina Franzin, Erez Eitan, Sara Rau, Alessandro Amaddeo, Alice Fachin, Adamo Pio d'Adamo, Giuliana Decorti, Gabriele Stocco, Egidio Barbi, Giorgio Cozzi
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引用次数: 0

摘要

在儿科急诊环境中,氯胺酮是用于手术镇静和镇痛的镇静剂中安全性最高的一种。然而,氯胺酮可引起呕吐和恢复期躁动。目前还没有研究通过检测微小核糖核酸等表观遗传因素来预测这些不良事件的发生。我们研究了神经元源性细胞外囊泡 microRNA 图谱,以预测氯胺酮诱发的儿童呕吐和恢复期躁动的发生。为此,研究人员开展了一项单中心前瞻性药物表观遗传学研究,并在2019年10月至2022年11月期间招募了50名接受手术镇静的儿童,以静脉注射氯胺酮作为唯一的镇静药物。通过新一代测序分析了血浆神经源细胞外囊泡中的 MiRNA 图谱,并在使用氯胺酮治疗前进行了测量。22名患者出现呕吐或恢复期躁动。在16个差异表达的microRNA中,上调的miR-15a-5p和miR-484靶向与N-甲基-D-天冬氨酸(NMDA)受体活性相关的基因,包括谷氨酸离子型受体NMDA型亚基2A(GRIN2A)。初步数据证实,发生这些事件的患者体内 GRIN2A 水平较低。下调的 miR-126-3p 和 miR-24-3p 针对 AMPA 受体相关基因。对基因靶点的功能分析显示,谷氨酸能和神经营养素信号传导丰富。恢复期躁动与这一网络有关。呕吐与多巴胺能和胆碱能系统有关。三个 miRNA(miR-18a-3p、miR-484 和 miR-548az-5p)被确定为氯胺酮诱发呕吐和恢复期躁动的预测性生物标志物(AUC 0.814;95% CI:0.632-0.956)。微RNA图谱可预测氯胺酮诱发的儿童呕吐或恢复期躁动的发生。这项研究有助于了解氯胺酮诱发不良事件的机制。
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Neuron-Derived Extracellular Vesicles miRNA Profiles Identify Children Who Experience Adverse Events after Ketamine Administration for Procedural Sedation.

Ketamine provides the highest safety profile among sedatives for procedural sedation and analgesia in the pediatric emergency setting. However, it can cause vomiting and recovery agitation. No studies have examined epigenetic factors, such as microRNAs, for predicting the occurrence of these adverse events. Neuronal-derived extracellular vesicle microRNA profiles were studied to predict the occurrence of ketamine-induced vomiting and recovery agitation in children. For this aim, a single-center prospective pharmacoepigenetic study was performed and 50 children who underwent procedural sedation with intravenous ketamine as the only sedative drug were enrolled between October 2019 and November 2022. MiRNA profiling in plasma neural-derived extracellular vesicles was analyzed through next-generation sequencing and measured before treatment with ketamine. Twenty-two patients experienced vomiting or recovery agitation. Among the 16 differentially expressed microRNAs, the upregulated miR-15a-5p and miR-484 targeted genes related to N-methyl-D-aspartate (NMDA) receptor activity, including glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A). Preliminary data confirmed lower GRIN2A levels in patients who developed these events. Downregulated miR-126-3p and miR-24-3p targeted AMPA receptor-associated genes. Functional analyses of gene targets revealed the enrichment of glutamatergic and neurotrophins signaling. Recovery agitation was associated with this network. Vomiting was related to dopaminergic and cholinergic systems. Three miRNAs (miR-18a-3p, miR-484, and miR-548az-5p) were identified as predictive biomarkers (AUC 0.814; 95% CI: 0.632-0.956) for ketamine-induced vomiting and recovery agitation. MicroRNA profiles can predict the development of ketamine-induced vomiting or recovery agitation in children. This study contributes to the understanding of the mechanisms underlying ketamine-induced adverse events.

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来源期刊
CiteScore
12.70
自引率
7.50%
发文量
290
审稿时长
2 months
期刊介绍: Clinical Pharmacology & Therapeutics (CPT) is the authoritative cross-disciplinary journal in experimental and clinical medicine devoted to publishing advances in the nature, action, efficacy, and evaluation of therapeutics. CPT welcomes original Articles in the emerging areas of translational, predictive and personalized medicine; new therapeutic modalities including gene and cell therapies; pharmacogenomics, proteomics and metabolomics; bioinformation and applied systems biology complementing areas of pharmacokinetics and pharmacodynamics, human investigation and clinical trials, pharmacovigilence, pharmacoepidemiology, pharmacometrics, and population pharmacology.
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