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七氟醚麻醉对大鼠海马的影响:基因组表达分析。

The effects of sevoflurane anesthesia on rat hippocampus: a genomic expression analysis.

机构信息

Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.

出版信息

Brain Res. 2011 Mar 24;1381:124-33. doi: 10.1016/j.brainres.2011.01.020. Epub 2011 Jan 15.

Abstract

Recent studies have shown that general anesthesia induces memory impairment. Sevoflurane, an inhalation anesthetic, is widely used in clinical practice, increasing pieces of evidence suggest that sevoflurane impairs memory processes due to changing gene expression in hippocampus. However, little is known about genome-widely analyzing the expression change induced by sevoflurane in hippocampus. In this study, we profiled the changes of hippocampal gene expression by microarray analysis. Six-week-old male Sprague-Dawley rats were anesthetized for 4h with 2.5% sevoflurane (n = 6) and were sacrificed 48 h later. RNA was extracted from the hippocampus for gene expression profile. Compared to control group, 417 genes, including up-regulated 67 and down-regulated 350, were significantly changed (> 2.0 or < -2.0 fold) (P < 0.05). Of these, there are 45 named genes, which are most involved in metabolism, development, biosynthesis, life material binding, location, signal transduction and communication, structural and vesicular processes. We randomly chose 6 differential genes to verify the microarray result. We also selected seven most differential genes, including 3 up-regulated genes (RMCP-1, Slc6a3, and Pitx2) and 4 down-regulated genes (VN7, AVP, IP10, and OT), to investigate whether there is a dose- or time-dependent effect of sevoflurane on gene expression. The result indicated that the microarray profile is reliable; there is no obvious dose-dependent effect of sevoflurane on gene expression. These results suggested that sevoflurane induced long-term (at least 2 days) expression change of the numerous genes in hippocampus, which may be related to the memory impairment or the other neural disorders.

摘要

最近的研究表明全身麻醉会导致记忆损伤。七氟醚作为一种吸入性麻醉剂,在临床实践中被广泛应用,越来越多的证据表明七氟醚通过改变海马体中的基因表达来损害记忆过程。然而,关于七氟醚在海马体中引起的全基因组表达变化的研究还知之甚少。在这项研究中,我们通过微阵列分析来描绘海马体基因表达的变化。将 6 周龄雄性 Sprague-Dawley 大鼠用 2.5%七氟醚麻醉 4 小时(n = 6),然后在 48 小时后处死。从海马体中提取 RNA 进行基因表达谱分析。与对照组相比,有 417 个基因(上调 67 个,下调 350 个)显著变化(> 2.0 或 < -2.0 倍)(P < 0.05)。其中有 45 个命名基因,它们主要涉及代谢、发育、生物合成、生命物质结合、定位、信号转导和通讯、结构和囊泡过程。我们随机选择了 6 个差异基因来验证微阵列结果。我们还选择了 7 个最差异基因,包括 3 个上调基因(RMCP-1、Slc6a3 和 Pitx2)和 4 个下调基因(VN7、AVP、IP10 和 OT),以研究七氟醚对基因表达是否存在剂量或时间依赖性效应。结果表明微阵列谱是可靠的;七氟醚对基因表达没有明显的剂量依赖性效应。这些结果表明,七氟醚诱导海马体中大量基因的长期(至少 2 天)表达变化,这可能与记忆损伤或其他神经障碍有关。

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