Department of Anatomy, Histology and Embryology, K.K. Leung Brain Research Center, Fourth Military Medical University, No. 169 West Changle Road, Xi'an, Shaanxi Province 710032, PR China.
Neuroscience. 2010 Jun 30;168(2):531-42. doi: 10.1016/j.neuroscience.2010.02.025. Epub 2010 Feb 16.
The delta opioid receptor (DOR) agonist [D-Ala2, D-Leu5] enkephalin (DADLE) has been implicated as a novel neuroprotective agent in the CNS. The current study was designed to evaluate the effects of intracerebroventricular (ICV) application of DADLE on neurological outcomes following asphyxial cardiac arrest (CA) in rats. Male Sprague-Dawley rats were randomly assigned to four groups: Sham group, CA group, DADLE group (DADLE+CA), and Naltrindole group (Naltrindole and DADLE+CA). All drugs were administered into the left cerebroventricle 30 min before CA. CA was induced by 8-min asphyxiation and the animals were resuscitated with a standardized method. DOR protein expression in the hippocampus was significantly increased in the CA group at 1 h after restoration of spontaneous circulation (ROSC) compared with the Sham group. As time progressed, expression of DOR proteins decreased gradually in the CA group. Treatment with DADLE alone or co-administration with Naltrindole reversed the down-regulation of DOR proteins in the hippocampus induced by CA at 24 h after ROSC. Compared with the CA group, the DADLE group had persistently better neurological functional recovery, as assessed by neurological deficit score (NDS) and Morris water maze trials. The number of surviving hippocampal CA1 neurons in the DADLE group was significantly higher than those in the CA group. However, administration of Naltrindole abolished most of the neuroprotective effects of DADLE. We conclude that ICV administration of DADLE 30 min before asphyxial CA has significant protective effects in attenuating hippocampal CA1 neuronal damage and neurological impairments, and that DADLE executes its effects mainly through DOR.
δ 阿片受体（DOR）激动剂[D-Ala2，D-Leu5]脑啡肽（DADLE）已被认为是中枢神经系统中一种新型的神经保护剂。本研究旨在评估脑室注射（ICV）DADLE 对大鼠窒息性心脏骤停（CA）后神经功能结局的影响。雄性 Sprague-Dawley 大鼠随机分为四组：假手术组、CA 组、DADLE 组（DADLE+CA）和 Naltrindole 组（Naltrindole 和 DADLE+CA）。所有药物均在 CA 前 30 分钟注入左侧脑室。CA 通过 8 分钟的窒息诱导，并用标准化方法进行复苏。与假手术组相比，在自主循环恢复（ROSC）后 1 小时，CA 组海马 DOR 蛋白表达显著增加。随着时间的推移，CA 组 DOR 蛋白表达逐渐下降。单独使用 DADLE 或与 Naltrindole 共同给药可逆转 CA 后 ROSC 24 小时海马 DOR 蛋白的下调。与 CA 组相比，DADLE 组持续具有更好的神经功能恢复，如神经功能缺损评分（NDS）和 Morris 水迷宫试验评估。DADLE 组海马 CA1 神经元存活数明显高于 CA 组。然而，Naltrindole 的给药消除了 DADLE 的大部分神经保护作用。我们得出结论，ICV 给予 DADLE 在窒息性 CA 前 30 分钟具有减轻海马 CA1 神经元损伤和神经损伤的显著保护作用，DADLE 主要通过 DOR 发挥作用。
