Neuroscience Program, Department of Biological Sciences, Smith College, Ford Hall 235a, Northampton, MA 01063, USA.
Anesth Analg. 2013 Mar;116(3):589-95. doi: 10.1213/ANE.0b013e31827b27b0. Epub 2013 Feb 11.
Although general anesthetics are recognized for their potential to render patients unconscious during surgery, exposure can also lead to long-term outcomes of both cellular damage and protection. As regards the latter, delayed anesthetic preconditioning is an evolutionarily conserved physiological response that has the potential for protecting against ischemic injury in a number of tissues. Although it is known that delayed preconditioning requires de novo protein synthesis, knowledge of anesthetic-regulated genes is incomplete. In this study, we used the conserved nature of preconditioning to analyze differentially regulated genes in 3 different rat tissues. We hypothesized that by selecting those genes regulated in multiple tissues, we could develop a focused list of gene candidates potentially involved in delayed anesthetic preconditioning.
Young adult male Sprague-Dawley rats were anesthetized with a 2% isoflurane/98% air mixture for 90 minutes. Immediately after anesthetic exposure, animals were euthanized and liver, kidney, and heart were removed and total RNA was isolated. Differential gene expression was determined using rat oligonucleotide gene arrays. Array data were analyzed to select for genes that were significantly regulated in multiple tissues.
All 3 tissues showed differentially regulated genes in response to a clinically relevant exposure to isoflurane. Analysis of coordinately regulated genes yielded a focused list of 34 potential gene candidates with a range of ontologies including regulation of inflammation, modulation of apoptosis, regulation of ion gradients, and maintenance of energy pathways.
Through using an analysis approach focusing on coordinately regulated genes, we were able to generate a focused list of interesting gene candidates with potential to enable future preconditioning studies.
尽管全身麻醉剂被认为具有使患者在手术过程中失去意识的潜力，但接触全身麻醉剂也会导致细胞损伤和保护的长期后果。就后者而言，延迟麻醉预处理是一种进化保守的生理反应，具有保护多种组织免受缺血性损伤的潜力。尽管已知延迟预处理需要新的蛋白质合成，但对麻醉调节基因的了解并不完整。在这项研究中，我们利用预处理的保守性来分析 3 种不同大鼠组织中差异调节的基因。我们假设，通过选择在多种组织中调节的基因，我们可以开发出一组潜在涉及延迟麻醉预处理的基因候选物的重点列表。
年轻成年雄性 Sprague-Dawley 大鼠用 2%异氟烷/98%空气混合物麻醉 90 分钟。麻醉暴露后立即处死动物，取出肝脏、肾脏和心脏，提取总 RNA。使用大鼠寡核苷酸基因芯片测定差异基因表达。对芯片数据进行分析，选择在多个组织中显著调节的基因。
所有 3 种组织对临床相关异氟烷暴露均显示出差异调节的基因。对协调调节基因的分析产生了 34 个潜在基因候选物的重点列表，其本体论范围包括炎症调节、凋亡调节、离子梯度调节和能量途径维持。
通过使用关注协调调节基因的分析方法，我们能够生成一组有趣的基因候选物的重点列表，这些候选物有可能为未来的预处理研究提供帮助。
