Tanaka Shunsuke, Ishikawa Masashi, Arai Masae, Genda Yuuki, Sakamoto Atsuhiro
Department of Anesthesiology and Pain Medicine, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
Biomed Res. 2012;33(5):255-63. doi: 10.2220/biomedres.33.255.
Reportedly, a large number of microRNAs (miRNAs) play an important role in inflammatory lung diseases such as asthma, idiopathic pulmonary fibrosis (IPF), acute respiratory distress syndrome (ARDS), and pulmonary arterial hypertension (PAH). Sevoflurane is routinely used to various patients, and its safety has been confirmed by clinical outcomes; however, its effects to lungs at the miRNA level have not been elucidated. In our previous genomic studies, we showed that sevoflurane anesthesia affected the expression of many genes and mRNAs in rat lungs. In this study, we comprehensively investigated changes in miRNA expression caused by sevoflurane anesthesia (2.0% and 4.0%). Sevoflurane anesthesia resulted in apparent changes in miRNA expression in rat lungs, and the pattern of 2.0% sevoflurane-induced changes in miRNA expression was similar to that of 4.0% sevoflurane. Some of the differentially expressed miRNAs are known to be involved in asthma, IPF, and PAH. Especially, miR-146a, the most up-regulated miRNA, is known to attenuate the toxic effects associated with LPS stimulation. We showed, for the first time, dynamic changes in miRNA expression caused by sevoflurane anesthesia, and moreover, our results were important to understand the influence of sevoflurane anesthesia on any patients suffered from various lung diseases.
据报道,大量的微小RNA(miRNA)在炎症性肺部疾病如哮喘、特发性肺纤维化(IPF)、急性呼吸窘迫综合征(ARDS)和肺动脉高压(PAH)中发挥重要作用。七氟醚常用于各类患者,其安全性已通过临床结果得到证实;然而,其在miRNA水平对肺部的影响尚未阐明。在我们之前的基因组研究中,我们表明七氟醚麻醉会影响大鼠肺中许多基因和mRNA的表达。在本研究中,我们全面研究了七氟醚麻醉(2.0%和4.0%)引起的miRNA表达变化。七氟醚麻醉导致大鼠肺中miRNA表达出现明显变化,2.0%七氟醚诱导的miRNA表达变化模式与4.0%七氟醚相似。一些差异表达的miRNA已知与哮喘、IPF和PAH有关。特别是,上调最明显的miR-146a已知可减轻与脂多糖刺激相关的毒性作用。我们首次展示了七氟醚麻醉引起的miRNA表达动态变化,此外,我们的结果对于理解七氟醚麻醉对任何患有各种肺部疾病患者的影响具有重要意义。