Department of Anesthesiology, Guizhou Provincial People's Hospital, Guiyang, 550002, PR China; Department of Anesthesiology, Guizhou University People's Hospital, Guiyang, 550002, PR China.
Department of Anesthesiology, West China Second University Hospital, Sichuan University, Chengdu, 610041, PR China.
Biomed Pharmacother. 2019 May;113:108671. doi: 10.1016/j.biopha.2019.108671. Epub 2019 Mar 12.
Hypoxic-ischemic brain damage (HIBD) is a major cause of acute mortality and chronic neurological morbidity in infants and children. Dexmedetomidine (DEX) is an effective choice in HIBD treatment. Recent findings have revealed that microRNA-128 (miR-128) is implicated in cerebral ischemia reperfusion. Hence, this study aimed to investigate the role of miR-128 in HIBD.
HIBD models of neonatal mice were established. HIBD mice were treated with DEX, and injected with agomir (ago)-miR-128 or antagomir (anti)-miR-128 into the lateral ventricles to explore the influence of miR-128 on the neuroprotective effects of DEX on HIBD. Subsequently, the mice body weight, left/right (L/R) brain weight ratio, left-brain water content as well as learning and memory abilities were measured. Furthermore, the pathological changes of brain tissues and apoptosis rate of nerve cells were determined. The potential relationship between miR-128 and WNT1 was analyzed.
Over-expression of miR-128 caused an increase in mouse body weight, L/R brain weight ratio, and learning and memory abilities, while led to a decline in left-brain water content, brain tissue injury and apoptosis rate of nerve cells in DEX-treated HIBD mice. WNT1 was targeted and negatively regulated by miR-128. Silencing of WNT1 exerted the same effect as miR-128 on enhancing the neuroprotective effect of DEX on HIBD mice.
Collectively, miR-128 enhanced neuroprotective effect of DEX on HIBD neonatal mice by inhibiting WNT1.
缺氧缺血性脑损伤（HIBD）是婴儿和儿童急性死亡和慢性神经发育障碍的主要原因。右美托咪定（DEX）是 HIBD 治疗的有效选择。最近的研究结果表明，微小 RNA-128（miR-128）与脑缺血再灌注有关。因此，本研究旨在探讨 miR-128 在 HIBD 中的作用。
建立新生小鼠 HIBD 模型。HIBD 小鼠用 DEX 处理，并向侧脑室注射 agomir（ago）-miR-128 或 antagomir（anti）-miR-128，以探讨 miR-128 对 DEX 对 HIBD 的神经保护作用的影响。随后，测量小鼠体重、左右（L/R）脑重比、左脑含水量以及学习和记忆能力。进一步，测定脑组织病理变化和神经细胞凋亡率。分析 miR-128 与 WNT1 之间的潜在关系。
miR-128 的过表达导致小鼠体重、L/R 脑重比和学习记忆能力增加，而 DEX 处理的 HIBD 小鼠左脑含水量、脑组织损伤和神经细胞凋亡率降低。WNT1 是 miR-128 的靶基因，并受到 miR-128 的负调控。沉默 WNT1 对增强 DEX 对 HIBD 小鼠的神经保护作用与 miR-128 相同。
综上所述，miR-128 通过抑制 WNT1 增强了 DEX 对 HIBD 新生小鼠的神经保护作用。
