七氟醚后处理可改善空间学习和记忆功能障碍通过减弱内质网应激反应引起的失血性休克和复苏的大鼠模型的神经元细胞凋亡
Postconditioning with sevoflurane ameliorates spatial learning and memory deficit via attenuating endoplasmic reticulum stress induced neuron apoptosis in a rat model of hemorrhage shock and resuscitation.
背景与目的：
出血休克可以引发内质网应激（ERS），然后诱导神经细胞凋亡。
这项研究的目的是为了研究七氟醚的后置条件是否能通过抑制由ERS引起的细胞凋亡来减轻大脑损伤。
1
方法：
70只雄性大鼠随机分为5组：假手术组、休克组、低浓度七氟醚后处理组（sevo1、1.2%）、中等浓度七氟醚后处理组（sevo2、2.4%）和高浓度七氟醚后处理组（sevo3，3.6%）。
出血性休克是通过在30分钟内去除总血容量的40%造模。完成后1h,出血的大鼠都在接下来的30分钟内进行再灌注。大鼠的空间学习和记忆能力是由莫里斯水迷宫测试在手术后三天(MWM)进行评估。在MWM测试后，对海马CA1区域的末端脱氧核糖核酸转移酶介导的dUTP切口末端标记法（TUNEL）呈阳性的细胞进行了评估。
再灌注24h后，对海马体内的 C/EBPhomologousprotein 即 C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白（CHOP）和葡萄糖调节蛋白78（GRP78）进行测定。
结果：
使用2.4%和3.6%的七氟醚后处理，显著改善了空间学习和记忆能力，减少了原位末端标记法TUNEL-阳性的细胞，与休克组相比GRP78和CHOP表达减少。
结论：
浓度为2.4%和3.6%的七氟醚用于后处理，可以通过抑制由ERS诱导的细胞凋亡来改善出血性休克和复苏损伤的空间学习和记忆功能障碍
Abstract
Hemorrhage shock could initiate endoplasmic reticulum stress (ERS) and then induce neuronal apoptosis. The aim of this study was to investigate whether sevoflurane postconditioning could attenuate brain injury via suppressing apoptosis induced by ERS. Seventy male rats were randomized into five groups: sham, shock, low concentration (sevo1, 1.2%), middle concentration (sevo2, 2.4%) and high concentration (sevo3, 3.6%) of sevoflurane postconditioning. Hemorrhage shock was induced by removing 40% of the total blood volume during an interval of 30 min. 1 h after the completion of bleeding, the animals were reinfused with shed blood during the ensuing 30 min. The spatial learning and memory ability of rats were measured by Morris water maze (MWM) test three days after the operation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region were assessed after the MWM test. The expression of C/EBP-homologousprotein (CHOP) and glucose-regulated protein 78 (GRP78) in the hippocampus were measured at 24 h after reperfusion. We found that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% significantly ameliorated the spatial learning and memory ability, decreased the TUNEL-positive cells, and reduced the GRP78 and CHOP expression compared with the shock group. These results suggested that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% could ameliorate spatial learning and memory deficit after hemorrhage shock and resuscitation injury via suppressing apoptosis induced by ERS.
麻醉学文献进展分享
联系我们