Background: Dexmedetomidine (Dex) is widely used in perioperative anesthesia, and recent studies have reported that it protects organs from ischemia/reperfusion (I/R) injury. Objectives: This study was performed to investigate the role of Dex in alleviating cerebral I/R injury and its regulatory effects on metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-140-5p (miR-140-5p)/nuclear factor erythroid-derived 2-like 2 (Nrf2) axis. Methods: In vivo rat middle cerebral artery occlusion (MCAO) model and in vitro oxygen-glucose deprivation/re-oxygenation (OGD/R)-induced neuronal injury model were constructed. Dex was injected into the animals or used to culture HT22 cells to observe the pharmacological effects. The neurological defect, brain water content, infarct volume of the rats, and neuron viability were evaluated. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were detected. Besides, the regulatory effects of Dex on MALAT1, miR-140-5p, and Nrf2 expression levels and regulatory relationships among them were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and dual- luciferase reporter assay. Results: Dex significantly alleviated the neurological injury of rats with MCAO and promoted the viability of neurons. Dex treatment suppressed miR-140-5p expression, but elevated MALAT1 and Nrf2 expressions. MALAT1 knockdown down-regulated Nrf2 expression and promoted oxidative stress in neurons. Additionally, miR-140-5p directly targeted Nrf2, and it also functioned as a downstream target miRNA of MALAT1. Conclusion: Dex, via regulating MALAT1/miR-140-5p/Nrf2 axis, plays a neuroprotective role against I/R-induced brain injury.

中文翻译：

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右美托咪定通过调节转移相关肺腺癌转录本 1/MicroRNA-140-5p/核因子红细胞衍生 2 样 2 轴减轻脑缺血/再灌注损伤

背景：右美托咪定（Dex）广泛用于围手术期麻醉，最近的研究报道其可保护器官免受缺血/再灌注（I/R）损伤。目的：探讨Dex在减轻脑缺血再灌注损伤中的作用及其对转移相关肺腺癌转录物1（MALAT1）/microRNA-140-5p（miR-140-5p）/核因子的调节作用红细胞衍生的 2 样 2 (Nrf2) 轴。方法：构建体内大鼠大脑中动脉闭塞（MCAO）模型和体外氧糖剥夺/复氧（OGD/R）诱导的神经元损伤模型。将Dex注射到动物体内或用于培养HT22细胞以观察药理作用。评估大鼠的神经缺损、脑含水量、梗塞体积和神经元活力。检测活性氧（ROS）、丙二醛（MDA）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的水平。此外，通过实时定量聚合酶链式反应（qRT-PCR）、Western blot和双荧光素酶报告基因测定评估了Dex对MALAT1、miR-140-5p和Nrf2表达水平的调节作用以及它们之间的调节关系。 。结果：Dex显着减轻MCAO大鼠的神经损伤，促进神经元活力。Dex 治疗抑制 miR-140-5p 表达，但升高 MALAT1 和 Nrf2 表达。MALAT1 敲除下调 Nrf2 表达并促进神经元氧化应激。此外，miR-140-5p直接靶向Nrf2，并且还充当MALAT1的下游靶miRNA。结论：Dex通过调节MALAT1/miR-140-5p/Nrf2轴，对缺血再灌注引起的脑损伤发挥神经保护作用。