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本公众号每天分享一篇最新一期Anesthesia & Analgesia等SCI杂志的摘要翻译，敬请关注并提出宝贵意见 Propofol Alters Long Non-Coding RNA Profiles in the Neonatal Mouse Hippocampus: Implication of Novel Mechanisms in Anesthetic-Induced Developmental Neurotoxicity 背景与目的 异丙酚诱导产生急性神经毒性（例如神经细胞凋亡），随之损害动物的长期记忆和学习。但是，基本机制很大程度上仍然未知。长链非编码RNA（lncRNA）参与各种病理过程。我们假设lncRNA序列和相关的信号通路被改变，这些改变可能与异丙酚诱导后新生小鼠海马中观察到的神经毒性有关。 方 法 在该实验中，将小鼠按每组四只分为四组，对新生小鼠（七天）使用亚麻醉剂量的丙泊酚3小时。异丙酚给药后3小时收集海马组织。使用比色测定法测定半胱天冬蛋白酶-3的活性以此分析神经细胞凋亡情况。使用基因芯片技术研究35,923个lncRNA和24,881个信使RNA（mRNA）的序列。使用逆转录定量聚合酶链反应验证差异性表达的lncRNA和mRNA。对异丙酚引起的mRNAs和50种最严重的lncRNA调节异常进行了生物信息学分析，以探讨异丙酚神经毒性的可能机制和信号网络。 结 果 异丙酚诱导海马神经细胞凋亡，以及159个lncRNA和100个mRNA的差异表达（倍数变化±2.0，P <0.05）。生物信息学分析表明，这些lncRNA及其相关mRNA可能参与神经退行性途径（例如钙处理，细胞凋亡，自噬和突触发生）。 结 论 这篇新颖的报告强调异丙酚改变了lncRNAs，mRNAs及其协同信号网络，这为研究麻醉药物诱导的发育性神经退行性变的分子机制和神经毒性的预防靶点提供了新的思路。 原始文献摘要 Abstract Background: Propofol induces acute neurotoxicity (e.g., neuroapoptosis) followed by impairment of long-term memory and learning in animals. However, underlying mechanisms remain largely unknown. Long non-coding RNAs (lncRNAs) are found to participate in various pathological processes. We hypothesized that lncRNA profile and the associated signaling pathways were altered, and these changes might be related to the neurotoxicity observed in the neonatal mouse hippocampus following propofol exposure。 Methods: In this laboratory experiment, 7-day-old mice were exposed to a subanesthetic dose of propofol for 3 hours, with 4 animals per group. Hippocampal tissues were harvested 3 hours after propofol administration. Neuroapoptosis was analyzed based on caspase 3 activity using a colorimetric assay. A microarray was performed to investigate the profiles of 35,923 lncRNAs and 24,881 messenger RNAs (mRNAs). Representative differentially expressed lncRNAs and mRNAs were validated using reverse transcription quantitative polymerase chain reaction. All mRNAs dysregulated by propofol and the 50 top-ranked, significantly dysregulated lncRNAs were subject to bioinformatics analysis for exploring the potential mechanisms and signaling network of propofol-induced neurotoxicity. Results: Propofol induced neuroapoptosis in the hippocampus, with differential expression of 159 lncRNAs and 100 mRNAs (fold change ±2.0, P<0.05). Bioinformatics analysis demonstrated that these lncRNAs and their associated mRNAs might participate in neurodegenerative pathways (e.g., calcium handling, apoptosis,autophagy, and synaptogenesis). Conclusion: This novel report emphasizes that propofol alters profiles of lncRNAs, mRNAs, and their cooperative signaling network, which provides novel insights into molecular mechanisms of anesthetic-induced developmental neurodegeneration and preventive targets against the neurotoxicity. 麻醉学文献进展分享 贵州医科大学高鸿教授课题组 编辑：代东君 审校：李华宇 |
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