Department of Anesthesiology, University of Vermont Larner College of Medicine, 111 Colchester Avenue, Burlington, VT, 05401, USA.
Department of Neurological Sciences, University of Vermont Larner College of Medicine, Burlington, USA.
J Anesth. 2019 Dec;33(6):670-679. doi: 10.1007/s00540-019-02695-5. Epub 2019 Oct 14.
To evaluate the effects of sex on miRNA expression in the hippocampus after isoflurane anesthesia in a neonatal piglet model.
Six male and 6 female piglets, aged 3-5 days, were anesthetized with 2% isoflurane in room air for 3 h. Full physiologic monitoring was observed. Untreated animals (6 male, 6 female) served as controls. Expression of miRNAs in hippocampus was assessed.
In controls, miRNA expression in the hippocampus was highly conserved between males and females. However, 17/326 displayed sex-dependent differences: 10 miRNAs were more highly expressed in males; 7 showed lower expression in males than females. Isoflurane was associated with changes in the expression of distinct subsets of miRNAs in both males and females. In females, 14/326 miRNAs were significantly changed (3 downregulated; 11 upregulated); in males, 17/326 miRNAs were changed (7 downregulated; 10 upregulated). There was no overlap in significantly changed miRNAs between isoflurane-exposed males and females.
In the neonatal piglet hippocampus, miRNA expression was highly conserved. There was no overlap in miRNA expression between isoflurane-exposed males and females, suggesting sex differences in isoflurane-induced miRNA expression. These results support the hypothesis that a clinically relevant exposure to isoflurane induces distinct miRNA signatures in the hippocampus of neonatal male and female piglets. Their functional relevance in anesthesia-induced neurotoxicity remains unknown, although changes in specific miRNAs may either contribute to or protect against anesthesia-induced neurotoxicity.
在新生仔猪模型中评估异氟醚麻醉后海马中 miRNA 表达的性别差异。
6 只雄性和 6 只雌性仔猪，3-5 日龄，在空气环境中吸入 2%异氟醚麻醉 3 小时。进行全面的生理监测。未处理的动物（6 只雄性，6 只雌性）作为对照组。评估海马中的 miRNA 表达。
在对照组中，雄性和雌性之间海马中的 miRNA 表达高度保守。然而，有 17/326 个 miRNA 显示出性别依赖性差异：10 个 miRNA 在雄性中表达更高；7 个 miRNA 在雄性中表达低于雌性。异氟醚与雄性和雌性中不同 miRNA 子集的表达变化相关。在雌性中，有 14/326 个 miRNA 发生显著变化（3 个下调；11 个上调）；在雄性中，有 17/326 个 miRNA 发生变化（7 个下调；10 个上调）。在异氟醚暴露的雄性和雌性之间，没有显著变化的 miRNA 重叠。
在新生仔猪海马中，miRNA 表达高度保守。异氟醚暴露的雄性和雌性之间 miRNA 表达没有重叠，这表明异氟醚诱导的 miRNA 表达存在性别差异。这些结果支持了一个假说，即临床上相关的异氟醚暴露会在新生雄性和雌性仔猪的海马中诱导不同的 miRNA 特征。它们在麻醉诱导的神经毒性中的功能相关性尚不清楚，尽管特定 miRNA 的变化可能有助于或防止麻醉诱导的神经毒性。
