δ-阿片受体和μ-阿片受体参与重复电针预处理诱导的大鼠迟发性脑缺血耐受

Involvement of delta-and mu-opioid receptors in the delayed cerebral ischemic tolerance induced by repeated electroacupuncture preconditioning in rats.

作者信息

Xiong Li-ze, Yang Jing, Wang Qiang, Lu Zhi-hong

机构信息

Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

出版信息

Chin Med J (Engl). 2007 Mar 5;120(5):394-9.

PMID:17376310

Abstract

BACKGROUND

Preconditioning with repeated electroacupuncture (EA) could mimic ischemic preconditioning to induce cerebral ischemic tolerance in rats. The present study was designed to investigate whether mu (micro)-, delta (delta)- or kappa (kappa)-opioid receptors are involved in the neuroprotection induced by repeated EA preconditioning.

METHODS

The rats were pretreated with naltrindole (NTI), nor-binaltorphimine (nor-BNI) or D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), which is a highly selective delta-, kappa- or micro-opioid receptor antagonist respectively, before each EA preconditioning (30 minutes per day, 5 days). Twenty-four hours after the last EA treatment, the middle cerebral artery occlusion (MCAO) was induced for 120 minutes. The brain infarct volume was determined with 2, 3, 5-triphenyltetrazolium chloride staining at 24 hours after MCAO and compared with that in rats which only received EA preconditioning. In another experiment, the met-enkephalin-like immunoreactivity in rat brain was investigated by immunohistochemistry in both EA preconditioning and control rats.

RESULTS

The EA preconditioning reduced brain infarct volume compared with the control rats (P = 0.000). Administration of both NTI and CTOP attenuated the brain infarct volume reduction induced by EA preconditioning, presenting with larger infarct volume than that in the EA preconditioning rats (P < 0.001). But nor-BNI administration did not block the infarct volume reduction induced by EA preconditioning, presenting with smaller infarct volume than the control group rats (P = 0.000). The number of met-enkephalin-like immunoreactivity positive neurons in the EA preconditioning rats was more than that of the control rats (P = 0.000).

CONCLUSION

Repeated EA preconditioning stimulates the release of enkephalins, which may bind delta- and micro-opioid receptors to induce the tolerance against focal cerebral ischemia.

摘要

背景

重复电针预处理可模拟缺血预处理诱导大鼠脑缺血耐受。本研究旨在探讨μ（微）、δ（德尔塔）或κ（卡帕）阿片受体是否参与重复电针预处理诱导的神经保护作用。

方法

在每次电针预处理（每天30分钟，共5天）前，分别用纳曲吲哚（NTI）、去甲二氢吗啡酮（nor-BNI）或D-苯丙氨酸-半胱氨酸-酪氨酸-D-色氨酸-鸟氨酸-苏氨酸-苯丙氨酸-苏氨酸-氨基（CTOP）预处理大鼠，它们分别是高度选择性的δ、κ或μ阿片受体拮抗剂。最后一次电针治疗24小时后，诱导大脑中动脉闭塞（MCAO）120分钟。在MCAO后24小时，用2,3,5-三苯基四氮唑氯化物染色法测定脑梗死体积，并与仅接受电针预处理的大鼠进行比较。在另一项实验中，通过免疫组织化学研究电针预处理大鼠和对照大鼠脑内甲硫氨酸脑啡肽样免疫反应性。

结果

与对照大鼠相比，电针预处理减少了脑梗死体积（P = 0.000）。给予NTI和CTOP均减弱了电针预处理诱导的脑梗死体积减小，梗死体积比电针预处理大鼠大（P < 0.001）。但给予nor-BNI并未阻断电针预处理诱导的梗死体积减小，梗死体积比对照组大鼠小（P = 0.000）。电针预处理大鼠中甲硫氨酸脑啡肽样免疫反应性阳性神经元数量多于对照大鼠（P = 0.000）。