Paeschke Nadine, von Haefen Clarissa, Endesfelder Stefanie, Sifringer Marco, Spies Claudia D
Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
Department of Neonatology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Augustenburger Platz 1, 13353 Berlin, Germany.
Int J Mol Sci. 2017 Aug 23;18(9):1830. doi: 10.3390/ijms18091830.
During surgery or infection, peripheral inflammation can lead to neuroinflammation, which is associated with cognitive impairment, neurodegeneration, and several neurodegenerative diseases. Dexmedetomidine, an α-2-adrenoceptor agonist, is known to exert anti-inflammatory and neuroprotective properties and reduces the incidence of postoperative cognitive impairments. However, on the whole the molecular mechanisms are poorly understood. This study aims to explore whether dexmedetomidine influences microRNAs (miRNAs) in a rat model of lipopolysaccharide (LPS)-induced neuroinflammation. Adult Wistar rats were injected with 1 mg/kg LPS intraperitoneal (i.p.) in the presence or absence of 5 µg/kg dexmedetomidine. After 6 h, 24 h, and 7 days, gene expressions of interleukin 1-β (), tumor necrosis factor-α (), and microRNA expressions of miR 124, 132, 134, and 155 were measured in the hippocampus, cortex, and plasma. Dexmedetomidine decreased the LPS-induced neuroinflammation in the hippocampus and cortex via significant reduction of the and gene expressions after 24 h. Moreover, the LPS-mediated increased expressions of miR 124, 132, 134, and 155 were significantly decreased after dexmedetomidine treatment in both brain regions. In plasma, dexmedetomidine significantly reduced LPS-induced miR 155 after 6 h. Furthermore, there is evidence that miR 132 and 134 may be suitable as potential biomarkers for the detection of neuroinflammation.
在手术或感染期间，外周炎症可导致神经炎症，这与认知障碍、神经退行性变以及几种神经退行性疾病有关。右美托咪定是一种α-2肾上腺素能受体激动剂，已知具有抗炎和神经保护特性，并可降低术后认知障碍的发生率。然而，总体而言，其分子机制尚不清楚。本研究旨在探讨右美托咪定是否会在脂多糖（LPS）诱导的神经炎症大鼠模型中影响微小RNA（miRNA）。成年Wistar大鼠在有或无5μg/kg右美托咪定的情况下腹腔注射1mg/kg LPS。6小时、24小时和7天后，测量海马体、皮质和血浆中白细胞介素1-β（）、肿瘤坏死因子-α（）的基因表达以及miR 124、132、134和155的miRNA表达。24小时后，右美托咪定通过显著降低和基因表达，减轻了LPS诱导的海马体和皮质神经炎症。此外，在两个脑区，右美托咪定治疗后，LPS介导的miR 124、132、134和155表达增加显著降低。在血浆中，右美托咪定在6小时后显著降低了LPS诱导的miR 155。此外，有证据表明miR 132和134可能适合作为检测神经炎症的潜在生物标志物。
