Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China.
Eur J Clin Pharmacol. 2021 Dec;77(12):1853-1859. doi: 10.1007/s00228-021-03178-x. Epub 2021 Jul 3.
The aim of this study was to investigate the expression levels of plasma miR-30a-5p, miR-101-3p, miR-140-3p and miR-141-3p and their relationship to dexmedetomidine efficacy and adverse effects in pediatric patients.
The expression levels of miR-30a-5p, miR-101-3p, miR-140-3p and miR-141-3p were measured by qRT-PCR in plasma of 133 pediatric patients receiving dexmedetomidine for preoperative sedation. We analyzed the relationship between miRNA abundance and dexmedetomidine response, including sedative effect and adverse effects, and assessed the predictive power of miRNAs for drug response.
Among 133 pediatric patients, 111 patients were dexmedetomidine responders (UMSS ≥ 2) and 22 patients were non-responders (UMSS < 2). We observed higher expression levels of miR-101-3p and miR-140-3p in dexmedetomidine responders compared with non-responders (P < 0.05, P < 0.0001). In contrast, there was no significant difference in the expression levels of miR-30a-5p and miR-141-3p between responders and non-responders (P > 0.05). The plasma levels of miR-101-3p and miR-30a-5p were markedly downregulated in patients who experienced hypotension and bradycardia, respectively (P < 0.05). MiR-101-3p and miR-140-3p demonstrated a potential discriminatory ability between dexmedetomidine responders and non-responders, with AUC of 0.64 (P < 0.05) and 0.77 (P < 0.0001), respectively. The AUC of miR-101-3p in distinguishing patients without hypotension was 0.63 (P < 0.05). The AUC of miR-30a-5p in distinguishing patients without bradycardia was 0.74 (P < 0.05).
Our study demonstrated that circulating miR-101-3p, miR-140-3p and miR-30a-5p might be used as a blood-based marker for dexmedetomidine efficacy and safety in pediatric patients.
本研究旨在探讨血浆 miR-30a-5p、miR-101-3p、miR-140-3p 和 miR-141-3p 的表达水平及其与小儿患者右美托咪定疗效和不良反应的关系。
通过 qRT-PCR 检测 133 例接受右美托咪定术前镇静的小儿患者血浆中 miR-30a-5p、miR-101-3p、miR-140-3p 和 miR-141-3p 的表达水平。我们分析了 miRNA 丰度与右美托咪定反应(包括镇静效果和不良反应)之间的关系,并评估了 miRNA 对药物反应的预测能力。
在 133 例小儿患者中,111 例患者为右美托咪定反应者(UMSS≥2),22 例患者为非反应者(UMSS<2)。与非反应者相比,反应者的 miR-101-3p 和 miR-140-3p 表达水平更高(P<0.05,P<0.0001)。miR-30a-5p 和 miR-141-3p 的表达水平在反应者和非反应者之间无显著差异(P>0.05)。发生低血压和心动过缓的患者,血浆 miR-101-3p 和 miR-30a-5p 水平明显下调(P<0.05)。miR-101-3p 和 miR-140-3p 对右美托咪定反应者和非反应者具有潜在的鉴别能力,AUC 分别为 0.64(P<0.05)和 0.77(P<0.0001)。miR-101-3p 鉴别无低血压患者的 AUC 为 0.63(P<0.05)。miR-30a-5p 鉴别无心动过缓患者的 AUC 为 0.74(P<0.05)。
本研究表明,循环 miR-101-3p、miR-140-3p 和 miR-30a-5p 可能可作为小儿患者右美托咪定疗效和安全性的一种基于血液的标志物。