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使用磷-31磁共振波谱法测量发现,NMDA拮抗剂MK-801可改善大鼠全脑缺血10分钟后的代谢恢复情况。

The NMDA antagonist MK-801 improved metabolic recovery after 10 minutes global cerebral ischaemia in rats measured with 31 phosphorous magnetic resonance spectroscopy.

作者信息

Haraldseth O, Grønås T, Southon T E, Jynge P, Gisvold S E, Unsgård G

机构信息

Department of Pharmacology and Toxicology, University of Trondheim, Norway.

出版信息

Acta Neurochir (Wien). 1990;106(1-2):32-6. doi: 10.1007/BF01809330.

Abstract

The blockade of postsynaptic receptors for excitatory amino acids is a promising new field for the possible treatment of cerebral ischaemia. The most important receptor seems to be the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptors and MK-801 is a potent non-competitive antagonist to the NMDA receptor. 31P NMR Spectroscopy was used to measure the recovery of intracellular pH and the high energy phosphates Phosphocreatine (PCr) and ATP after ten minutes of temporary global cerebral ischaemia in the rat. Cerebral ischaemia was obtained by combining bilateral carotid ligation and systemic hypotension (2 vessel occlusion model). Two intervention groups with intravenous injection of MK-801 in doses of 0.25 mg/kg and 0.5 mg/kg 15 minutes before onset of ischaemia were compared to a control group. Both intervention groups showed a more rapid recovery of PCr and ATP than the control group, but there were no significant differences for intracellular pH.

摘要

阻断兴奋性氨基酸的突触后受体是治疗脑缺血一个很有前景的新领域。最重要的受体似乎是谷氨酸受体的N-甲基-D-天冬氨酸(NMDA)亚型,而MK-801是NMDA受体的一种强效非竞争性拮抗剂。利用31P核磁共振波谱法测量大鼠全脑短暂缺血10分钟后细胞内pH值以及高能磷酸盐磷酸肌酸(PCr)和三磷酸腺苷(ATP)的恢复情况。通过双侧颈动脉结扎和全身低血压(双血管闭塞模型)造成脑缺血。将缺血发作前15分钟静脉注射0.25mg/kg和0.5mg/kg剂量MK-801的两个干预组与一个对照组进行比较。两个干预组的PCr和ATP恢复速度均比对照组更快,但细胞内pH值无显著差异。

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