国际麻醉学与复苏杂志   2011, Issue (6): 13-13
    
七氟醚对SD大鼠海马生物钟基因表达影响的研究
潘志强, 杨俊霞, 郝凌云, 朱丽娇, 鲁显福, 曹君利1()
1.江苏省麻醉学重点实验室
The effect of sevoflurane on the expression of circadian gene in SD rat hippocampus
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摘要:

目的 七氟醚麻醉会导致学习记忆损伤,但其分子机制并不清楚。前期研究中,我们利用基因芯片对SD大鼠海马的基因表达谱进行了分析,表明七氟醚能够改变海马内417个基因的表达。生物钟基因与生理节律调节密切相关,为研究七氟醚对该族基因的影响,我们进一步调查了七氟醚在使用剂量和时间上对生物钟基因表达的调控作用。 方法 用不同浓度七氟醚麻醉SD大鼠4小时(n=6/组),麻醉后不同时间分离海马组织并提取总RNA。然后,采用实时定量PCR方法进行定量检测和分析。 结果 表明被调查的6个生物钟基因Per2、Dbp、Arc、Egr1、Krox20和NGFI-B中,只有Egr和Per有明显的剂量依赖性,其它4个基因则无此关系。此外,6个生物钟基因均有明显时间依赖关系,随着麻醉后苏醒时间增加,其表达水平逐渐趋于正常。 结论 七氟醚对海马生物钟基因表达有较大影响,这种改变会持续较长时间(至少10天),这可能与七氟醚引起的学习记忆损伤有关。

关键词: 七氟醚;海马;生物钟基因;学习记忆损伤
Abstract:

Objective 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. In our previous study, we found sevoflurane changed the expression of 417 genes by using mircoarray. In the present study, we, in one hand, demonstrated the result of circadian gene expression from microarray detection during sevoflurane anesthesia; on the other hand, we investigated weather there were time-course or dose-dependent relation between sevoflurane and circadian gene expression. Methods In the expriment, six-week-old male Sprague-Dawley rats were anesthetized for 4 h with 2.5% sevoflurane (n=6) and were sacrificed 48 h later. RNA was extracted from the hippocampus, the gene expression was performed by real-time quantatitive PCR. Results The results indicated that among six circadian genes including Per2, Dbp, Arc, Egr1 and Krox20, only Egr and Per had dose-dependent relation, the other four genes had no obvious the relation. However, six genes had significant time-course relation.Their expression level tended to normal level 10 day after anesthesia. Conclusion Our conclusion is drawn out that sevofluran has an obvious effect on the expression of circadian genes in hippocampus, these changes could last long-term (at least 10 days) , which may be related to the memory impairment or the other neural disorders.

Key words: sevoflurane;hippocampus; circadian gene; memory impairment