Despite advances in obstetric and neonatal care, challenges remain in early identification of neonates with encephalopathy due to hypoxia-ischemia who are undergoing therapeutic hypothermia. Therefore, there is a deep search for biomarkers that can identify brain injury. The aims of this study were to investigate the serum and brain expressions of two potential biomarkers, miR-126/miR-146a, in a preclinical model of hypoxia-ischemia (HI)–induced brain injury, and to explore their modulation during melatonin treatment. Seven-day-old rats were subjected to permanent ligation of the right carotid artery followed by 2.5 h hypoxia (HI). Melatonin (15 mg/kg) was administered 5 min after HI. Serum and brain samples were collected 1, 6 and 24 h after HI. Results show that HI caused a significant increase in the circulating levels of both miR-126 and miR-146a during the early phase of ischemic brain damage development (i.e. 1 h), with a parallel and opposite pattern in the ischemic cerebral cortex. These effects are not observed 24 h later. Treatment with melatonin restored the HI-induced effects on miR-126/miR-146a expressions, both in the cerebral cortex and in serum. We conclude that miR-126/miR-146a are promising biomarkers of HI injury and demonstrate an associated change in concentration following melatonin treatment.

尽管产科和新生儿护理取得了进步，但在早期识别正在接受低温治疗的缺氧缺血性脑病新生儿方面仍然存在挑战。因此，人们正在深入寻找可以识别脑损伤的生物标志物。本研究的目的是在缺氧缺血 (HI) 诱导的脑损伤的临床前模型中研究两种潜在生物标志物 miR-126/miR-146a 的血清和大脑表达，并探讨它们在褪黑素治疗期间的调节作用。7日龄大鼠的右颈动脉被永久结扎，然后缺氧2.5小时（HI）。HI 后 5 分钟给予褪黑激素 (15 mg/kg)。HI 后 1、6 和 24 小时收集血清和脑样本。结果表明，在缺血性脑损伤发展的早期阶段（即1小时），HI导致miR-126和miR-146a的循环水平显着增加，在缺血性大脑皮层中具有平行和相反的模式。24 小时后不会观察到这些影响。褪黑激素治疗恢复了 HI 诱导的对大脑皮层和血清中 miR-126/miR-146a 表达的影响。我们得出的结论是，miR-126/miR-146a 是有希望的 HI 损伤生物标志物，并证明褪黑激素治疗后浓度会发生相关变化。