Adachi Naoto, Liu Keyue, Arai Tatsuru
Department of Anesthesiology and Resuscitology, Ehime University School of Medicine, Shitsukawa, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan.
Brain Res. 2004 Feb 13;998(1):136-8. doi: 10.1016/j.brainres.2003.11.020.
Inflammatory reactions play an important role in ischemia-reperfusion injury in the brain. Since histamine H(2) action suppresses inflammatory reactions, effects of postischemic loading with histidine, a precursor of histamine, were examined. Focal cerebral ischemia for 15 min was provoked by transient occlusion of the right middle cerebral artery in rats, and delayed neuronal death were evaluated in striatal neurons after 7 days. Histidine was administered four times, immediately, 6, 24, and 48 h after reperfusion of blood flow (1000 mg/kg, i.p., each time). To examine the role of histaminergic action on changes in histologic outcome, effects of mepyramine (3 nmol, i.c.v.), an H(1) antagonist, and ranitidine (30 nmol, i.c.v.), an H(2) antagonist, were evaluated in histidine-treated rats. Transient ischemia for 15 min provoked severe neuronal damage in the saline-injected control group, and the number of striatal neurons decreased to 21% of that on the contralateral side. Administration of histidine alleviated ischemic neuronal damage, and the number of preserved neurons was 76% of that on the contralateral side. Simultaneous administration of mepyramine with histidine did not affect the histologic outcome. However, administration of ranitidine abolished the alleviation by histidine. These findings indicate that the elevation of histamine H(2) receptor stimulation by massive administration of histidine suppresses reperfusion injury in the brain.
炎症反应在脑缺血再灌注损伤中起重要作用。由于组胺H(2)作用可抑制炎症反应，因此研究了缺血后给予组胺前体组氨酸的效果。通过短暂阻断大鼠右侧大脑中动脉诱发局灶性脑缺血15分钟，并在7天后评估纹状体神经元的迟发性神经元死亡。在血流再灌注后立即、6小时、24小时和48小时给予组氨酸4次（每次1000mg/kg，腹腔注射）。为了研究组胺能作用对组织学结果变化的作用，在给予组氨酸的大鼠中评估了H(1)拮抗剂美吡拉敏（3nmol，脑室内注射）和H(2)拮抗剂雷尼替丁（30nmol，脑室内注射）的效果。在注射生理盐水的对照组中，15分钟的短暂缺血诱发了严重的神经元损伤，纹状体神经元数量减少至对侧的21%。给予组氨酸可减轻缺血性神经元损伤，存活神经元数量为对侧的76%。美吡拉敏与组氨酸同时给药不影响组织学结果。然而，给予雷尼替丁可消除组氨酸的减轻作用。这些发现表明，大量给予组氨酸可提高组胺H(2)受体刺激，从而抑制脑再灌注损伤。
