BackgroundEmerging data suggests that volatile anesthetic agents may have organ protection properties in the setting of critical illness. The purpose of this study was to better understand the effect of inflammation on cerebral subcellular energetics in animals exposed to two different anesthetic agents—a GABA agonist (propofol) and a volatile agent (isoflurane).ResultsForty-eight Sprague–Dawley rats were anesthetized with isoflurane or propofol. In each group, rats were randomized to celiotomy and closure (sham) or cecal ligation and puncture (inflammation [sepsis model]) for 8 h. Brain tissue oxygen saturation and the oxidation state of cytochrome aa3 were measured. Brain tissue was extracted using the freeze-blow technique. All rats experienced progressive increases in tissue oxygenation and cytochrome aa3 reduction over time. Inflammation had no impact on cytochrome aa3, but isoflurane caused significant cytochrome aa3 reduction. During isoflurane (not propofol) anesthesia, inflammation led to an increase in lactate (+ 0.64 vs. − 0.80 mEq/L, p = 0.0061). There were no differences in ADP:ATP ratios between groups. In the isoflurane (not propofol) group, inflammation increased the expression of hypoxia-inducible factor-1α (62%, p = 0.0012), heme oxygenase-1 (67%, p = 0.0011), and inducible nitric oxide synthase (31%, p = 0.023) in the brain. Animals exposed to inflammation and isoflurane (but not propofol) exhibited increased expression of protein carbonyls (9.2 vs. 7.0 nM/mg protein, p = 0.0050) and S-nitrosylation (49%, p = 0.045) in the brain. RNA sequencing identified an increase in heat shock protein 90 and NF-κβ inhibitor mRNA in the inflammation/isoflurane group.ConclusionsIn the setting of inflammation, rats exposed to isoflurane show increased hypoxia-inducible factor-1α expression despite a lack of hypoxia, increased oxidative stress in the brain, and increased serum lactate, all of which suggest a relative increase in anaerobic metabolism compared to propofol. Differences in oxidative stress as well as heat shock protein 90 and NF-κβ inhibitor may account for the differential expression of cerebral hypoxia-inducible factor-1α during inflammation.

中文翻译：

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炎症对麻醉大鼠脑亚细胞能量学的影响

背景新数据表明，挥发性麻醉剂可能在危重疾病的情况下具有器官保护特性。本研究的目的是更好地了解炎症对暴露于两种不同麻醉剂——GABA 激动剂（丙泊酚）和挥发性药物（异氟烷）的动物脑亚细胞能量学的影响。 结果 48 只 Sprague-Dawley 大鼠被麻醉异氟醚或丙泊酚。在每组中，大鼠随机接受剖腹手术和闭合（假手术）或盲肠结扎和穿刺（炎症 [脓毒症模型]）8 小时。测量脑组织氧饱和度和细胞色素aa3的氧化状态。使用冷冻吹法提取脑组织。随着时间的推移，所有大鼠的组织氧合作用逐渐增加，细胞色素 aa3 减少。炎症对细胞色素 aa3 没有影响，但异氟醚导致细胞色素 aa3 显着减少。在异氟醚（非丙泊酚）麻醉期间，炎症导致乳酸增加（+ 0.64 vs. − 0.80 mEq/L，p = 0.0061）。各组之间的 ADP:ATP 比率没有差异。在异氟醚（非丙泊酚）组中，炎症增加了缺氧诱导因子-1α（62%，p = 0.0012）、血红素加氧酶-1（67%，p = 0.0011）和诱导型一氧化氮合酶（31%）的表达, p = 0.023) 在大脑中。暴露于炎症和异氟醚（但不是丙泊酚）的动物在大脑中表现出增加的蛋白质羰基（9.2 对 7.0 nM/mg 蛋白质，p = 0.0050）和 S-亚硝基化（49%，p = 0.045）的表达。RNA 测序确定了炎症/异氟醚组中热休克蛋白 90 和 NF-κβ 抑制剂 mRNA 的增加。结论在炎症环境中，尽管缺乏缺氧，但暴露于异氟醚的大鼠表现出缺氧诱导因子-1α 表达增加、脑中氧化应激增加和血清乳酸增加，所有这些都表明与丙泊酚相比无氧代谢相对增加. 氧化应激以及热休克蛋白 90 和 NF-κβ 抑制剂的差异可能是炎症期间脑缺氧诱导因子-1α 表达差异的原因。