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七氟醚预处理对大鼠海马脑片缺氧无糖损伤的保护作用:线粒体K_(ATP)通道的作用

王志萍, 张兆航, 曾因明, 江山, 汪曙蕖, 王胜

徐州医学院附属医院麻醉科,徐州医学院江苏省麻醉医学研究所.江苏,徐州 221002

摘要

利用离体海马脑片缺氧无糖(oxygen--glucose deprivation,OGD)损伤模型,探讨七氟醚预处理对神经细胞的保护作用及该作用与线粒体内膜ATP敏感钾通道(mitochondrial ATP--sensitive potassium channels,mitoK_(ATP)channels)的关系,随机将脑片用2%、4%、6%七氟醚,以及6%七氟醚复合mitoK_(ATP)通道阻滞剂5--羟基奎酸盐(5--hydroxydecanoic acid,5--HD)预处理30min,观察OGD损伤14min复氧1h期间顺向群峰电位(orthodromic population spike,OPS)的变化,并应用透射电镜观察细胞超微结构的改变。结果表明,与单纯OGD组相比,七氟醚预处理可使海马脑片OPS消失时间明显延长({sl P}＜0.01),使OPS明显恢复,其中4%、6%七氟醚组的恢复率均为71.4%({sl P}＜0.05 vs OGD),相应恢复程度为(61.0±42.3)%和(78.7±21.1)%({sl P}＜0.01),而且6%七氟醚的保护作用可被5--HD取消。OGD组的海马CA1区锥体细胞明显水肿,核膜皱缩、破裂,染色质聚集，线粒体肿胀畸形，嵴断裂或消失，而4％和6％七氟醚组仅见海马CA1区锥体细胞轻度水肿，核膜皱缩不明显，染色质均匀，线粒体轻度肿胀。结果提示七氟醚预处理对大鼠海马脑片OGD损伤有一定的保护作用，七氟醚的神经细胞保护作用与激活MitoK_(ATP)通道有关。

关键词： 七氟醚; 脑损伤; 顺向群峰电位; 线粒体内膜ATP敏感钾通道

Protective effect of sevoflurane preconditioning on oxygen--glucose deprivation injury in rat hippocampal slices:the role of mitochondrial K_(ATP) channels

Wang Zhiping, Zhang Zhaohang, Zeng Yinming, Jiang Shan, Wang Shuqu, Wang Sheng

Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical College, Jiangsu Province Institute of Anesthesiology.Xuzhou 221002，Jiangsu

Abstract

To investigate the neuroprotective effects of sevoflurane preconditioning and the role of mitochondrial K_(ATP) channels in oxygen-glucose deprivation injury in rats, we established oxygen-glucose deprivation injury model in rat hippocampal slices. The brain was rapidly removed, and the dissected hippocampus was sliced in cold artificial cerebrospinal fluid (ACSF) transversely to its longitudinal axis (400 #mu#m thick) with a Rotorslicer DTY-7700. Slices were placed on a nylon mesh in a recording chamber at 34℃ and humidified gas mixture (95% O_(2)/5% CO_(2)) was applied to the chamber at a flow rate of 1 L/min. After 2 hours of incubation, slices were randomly exposed to 2%, 4%, 6% sevoflurane or 6% sevoflurane combined with mitochondrial K_(ATP) channel blocker (5-hydroxydecanoic acid, 5-HD) under normal condition (95%O_(2)/5%CO_(2)) for 30 min. Fifteen minutes later, slices were exposed to 14-minute oxygen-glucose deprivation (OGD) followed by 1-hour reoxygenation，the changes of orthodromic population spike (OPS) at the end of reoxygenation were measured. The changes of ultrastructure of CA1 area 14-min OGD followed by 1-hour reoxygenation were detected with electron microscope. The results showed that sevoflurane preconditioning delayed the abolishing time of OPS (P<0.01) and increased significantly the recovery rate and the recovery amplitude of OPS compared with the OGD group. The recovery rate of OPS was 71.4% and 71.4% respectively in 4% and 6% sevoflurane preconditioning group (P<0.05), accordingly the recovery amplitude of OPS was (61.0±42.3)% and (78.7±21.1)% (P<0.01). The protective effect of 6% sevoflurane was blocked by 5-HD. Ultrastructural observation in the hippocampal CA1 region of the OGD group showed severe edema of the pyramidal cells, crimpled or ruptured nucleus membranes, aggregation of chromatin, and swelling of mitochondria,whereas in 4% and 6% sevoflurane groups these changes were less prominent. It is therefore suggested that sevoflurane preconditioning is capable to protect neurons from OGD injury in vitro and that the protective effect is related to the activation of mitochondrial K_(ATP) channels.

Key words: sevoflurane;cerebral injury;orthodromic population spike;mitochondrial ATP-sensitive potassium channels

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引用本文：

王志萍, 张兆航, 曾因明, 江山, 汪曙蕖, 王胜. 七氟醚预处理对大鼠海马脑片缺氧无糖损伤的保护作用:线粒体K_(ATP)通道的作用[J]. 生理学报 2006; 58 (3): .

Wang Zhiping, Zhang Zhaohang, Zeng Yinming, Jiang Shan, Wang Shuqu, Wang Sheng. Protective effect of sevoflurane preconditioning on oxygen--glucose deprivation injury in rat hippocampal slices:the role of mitochondrial K_(ATP) channels. Acta Physiol Sin 2006; 58 (3): (in Chinese with English abstract).