右美托咪定通过降低 microRNA-134-5p 介导的 NLRX1 下调减轻新生大鼠缺氧缺血性脑损伤。
Dexmedetomidine Alleviates Hypoxic-Ischemic Brain Damage in Neonatal Rats Through Reducing MicroRNA-134-5p-Mediated NLRX1 Downregulation.
机构信息
Department of Anesthesiology, The First Hospital of Changsha, Changsha 410011, Hunan, China.
出版信息
J Stroke Cerebrovasc Dis. 2022 May;31(5):106411. doi: 10.1016/j.jstrokecerebrovasdis.2022.106411. Epub 2022 Mar 5.
BACKGROUND
Dexmedetomidine (Dex) is a safe and effective anesthetic adjunct which also has neuroprotective roles. This study aimed to validate the role of Dex in hypoxic-ischemic brain damage (HIBD) in neonatal rats and the functional molecules.
METHODS
A neonatal rat model of HIBD was established and treated with Dex. The learning and memory abilities of rats were determined by Morris water maze tests. The left-hemisphere encephalatrophy, pathological changes, neuronal apoptosis, and inflammation in rat hippocampal tissues were examined to evaluate the treating effects of Dex on HIBD. Differentially expressed microRNAs (miRNAs) in rats with HIBD were screened using microarray analysis. Potential downstream molecules mediated by miR-134-5p were predicted using bioinformatics analysis. Altered expression of miR-134-5p and NLR family member X1 (NLRX1) was induced in rats after Dex treatment for rescue experiments.
RESULTS
Dex treatment significantly enhanced the learning and memory abilities of rats and reduced encephalatrophy in rats. It also alleviated pathological changes, neuronal apoptosis, and the production of pro-inflammatory cytokines in rat hippocampal tissues. miR-134-5p was significantly upregulated in rats with HIBD. Dex treatment reduced the expression of miR-134-5p. NLRX1 was a target gene of miR-134-5p and it reduced the phosphorylation of IκBα and p65, namely the activation of NF-κB signaling. Overexpression of miR-134-5p blocked, whereas overexpression of NLRX1 strengthened the protective effects of Dex on neonatal rats.
CONCLUSION
This study demonstrates that Dex treatment can alleviate HIBD in neonatal rats through restoring NLRX1 expression by suppressing miR-134-5p.
背景
右美托咪定（Dex）是一种安全有效的麻醉辅助药物，具有神经保护作用。本研究旨在验证 Dex 在新生大鼠缺氧缺血性脑损伤（HIBD）中的作用及其功能分子。
方法
建立新生大鼠 HIBD 模型并给予 Dex 治疗。通过 Morris 水迷宫试验测定大鼠的学习记忆能力。检测大鼠左半球脑萎缩、病理变化、海马组织神经元凋亡和炎症，评价 Dex 对 HIBD 的治疗作用。采用微阵列分析筛选 HIBD 大鼠差异表达的 microRNAs（miRNAs）。通过生物信息学分析预测 miR-134-5p 潜在的下游分子。通过 Dex 处理诱导大鼠 miR-134-5p 和 NLR 家族成员 X1（NLRX1）的表达改变进行挽救实验。
结果
Dex 治疗显著提高了大鼠的学习记忆能力，减轻了大鼠的脑萎缩。还缓解了大鼠海马组织的病理变化、神经元凋亡和促炎细胞因子的产生。HIBD 大鼠中 miR-134-5p 明显上调。Dex 治疗降低了 miR-134-5p 的表达。NLRX1 是 miR-134-5p 的靶基因，它降低了 IκBα 和 p65 的磷酸化，即 NF-κB 信号的激活。miR-134-5p 的过表达阻断了，而 NLRX1 的过表达则增强了 Dex 对新生大鼠的保护作用。
结论
本研究表明，Dex 治疗可通过抑制 miR-134-5p 恢复 NLRX1 表达，减轻新生大鼠 HIBD。
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