双相异氟烷诱导的预处理可改善体外培养大鼠脑的神经保护作用及细胞外信号调节蛋白激酶的作用。

Dual isoflurane-induced preconditioning improves neuroprotection in rat brain in vitro and the role of extracellular signal--regulated protein kinase.

作者信息

Wang Sheng, Guo Su-xiang, Dai Zhi-gang, Dong Xi-wei, Liu Yang, Jiang Shan, Wang Zhi-ping

机构信息

Department of Anesthesiology, Affiliated Hospital of Shihezi Medical School , Shihezi University , Shihezi 832008, China.

出版信息

Chin Med Sci J. 2011 Mar;26(1):36-42. doi: 10.1016/s1001-9294(11)60017-5.

DOI:10.1016/s1001-9294(11)60017-5

PMID:21496421

Abstract

OBJECTIVE

To test the ability of isoflurane-induced preconditioning against oxygen and glucose deprivation (OGD) injury in vitro.

METHODS

Rat hippocampal slices were exposed to 1 volume percentage (vol%), 2vol% or 3vol% isoflurane respectively for 20 minutes under normoxic conditions (95% O₂/5% CO₂) once or twice (12 slices in each group) before OGD, with 15-minute washout after each exposure. During OGD experiments, hippocampus slices were bathed with artificial cerebrospinal fluid (ACSF) lacking glucose and perfused with 95% N₂ and 5% CO₂ for 14 minutes, followed by a 30-minute reperfusion in normal ACSF. The CA1 population spike (PS) was measured and used to quantify the degree of neuronal function recovery after OGD. To assess the role of mitogen-activated protein kinases (MAPKs) in isoflurane preconditioning, U0126, an inhibitor of extracellular signal-regulated protein kinase (ERK1/2), and SB203580, an inhibitor of p38 MAPK, were used before two periods of 3vol% isoflurane exposure.

RESULTS

The degree of neuronal function recovery of hippocampal slices exposed to 1vol%, 2vol%, or 3vol% isoflurane once was 41.88%±9.23%, 55.05% ± 11.02%, or 63.18% ± 10.82% respectively. Moreover, neuronal function recovery of hippocampal slices exposed to 1vol%, 2vol%, or 3vol% isoflurane twice was 53.75% ± 12.04%, 63.50% ± 11.06%, or 76.25% ± 12.25%, respectively. Isoflurane preconditioning increased the neuronal function recovery in a dose-dependent manner. U0126 blocked the preconditioning induced by dual exposure to 3vol% isoflurane (6.13% ± 1.56%, P < 0.01) and ERK1/2 activities.

CONCLUSIONS

Isoflurane is capable of inducing preconditioning in hippocampal slices in vitro in a dose-dependent manner, and dual exposure to isoflurane with a lower concentration is more effective in triggering preconditioning than a single exposure. Isoflurane-induced neuroprotection might be involved with ERK1/2 activities.

摘要

目的

测试异氟烷诱导的预处理对体外氧糖剥夺（OGD）损伤的作用。

方法

在常氧条件（95% O₂/5% CO₂）下，将大鼠海马脑片分别暴露于1体积百分比（vol%）、2vol%或3vol%的异氟烷中20分钟，OGD前进行一次或两次暴露（每组12片脑片），每次暴露后有15分钟的洗脱期。在OGD实验中，海马脑片用无糖的人工脑脊液（ACSF）孵育，并用95% N₂和5% CO₂灌注14分钟，随后在正常ACSF中再灌注30分钟。测量CA1群体峰电位（PS），并用于量化OGD后神经元功能恢复的程度。为评估丝裂原活化蛋白激酶（MAPKs）在异氟烷预处理中的作用，在两次3vol%异氟烷暴露前使用细胞外信号调节蛋白激酶（ERK1/2）抑制剂U0126和p38 MAPK抑制剂SB203580。

结果

一次暴露于1vol%、2vol%或3vol%异氟烷的海马脑片的神经元功能恢复程度分别为41.88%±9.23%、55.05%±11.02%或63.18%±10.82%。此外，两次暴露于1vol%、2vol%或3vol%异氟烷的海马脑片的神经元功能恢复程度分别为53.75%±12.04%、63.50%±11.06%或76.25%±12.25%。异氟烷预处理以剂量依赖的方式增加了神经元功能恢复。U0126阻断了两次暴露于3vol%异氟烷诱导的预处理（6.13%±1.56%，P<0.01）以及ERK1/2活性。