Motoki Atsuko, Adachi Naoto, Semba Kazunori, Liu Keyue, Arai Tatsuru
Department of Anesthesiology and Resuscitology, Ehime University School of Medicine, Shitsukawa, Touon-shi, Ehime 791-0295, Japan.
Brain Res. 2005 Dec 20;1066(1-2):172-8. doi: 10.1016/j.brainres.2005.10.059. Epub 2005 Dec 5.
Inflammation is a factor in the aggravation of reperfusion injury after cerebral ischemia. Since histamine H(2) receptor stimulation suppresses inflammatory reactions, effects of the central histaminergic activation on brain infarction were examined in rats. Focal cerebral ischemia for 2 h was provoked by transient occlusion of the right middle cerebral artery, and the infarct size was determined by 2,3,5-triphenyltetrazolium chloride stain after 24 h. Effects of postischemic administration of thioperamide, an H(3) antagonist, and metoprine, an inhibitor of histamine-N-methyltransferase, were evaluated in rats treated with l-histidine, a precursor of histamine. Furthermore, effects of these agents on changes in the striatal histamine level were examined by a microdialysis procedure. Focal ischemia provoked marked damage in rats treated with l-histidine (1000 mg/kg) alone. Administration of l-histidine (1000 mg/kg) with either thioperamide (5 mg/kg) or metoprine (10 mg/kg) alleviated brain infarction. The size of brain infarction was 27% and 10% of that in animals treated solely with l-histidine, respectively. The combination treatment with thioperamide and metoprine decreased the size of brain infarction in rats given l-histidine (500 mg/kg), although protective effects were not clear without l-histidine. A marked increase in the histamine concentration was observed in the histidine plus metoprine group, the value being 363% of that in the saline-injected group after 2-3 h. The histamine concentrations in the histidine group and histidine plus thioperamide group were 188% and 248%, respectively. These findings indicate that facilitation of central histaminergic activity reduced the brain infarction.
炎症是脑缺血后再灌注损伤加重的一个因素。由于组胺H(2)受体刺激可抑制炎症反应，因此在大鼠中研究了中枢组胺能激活对脑梗死的影响。通过短暂阻断右侧大脑中动脉引发2小时的局灶性脑缺血，并在24小时后用2,3,5-三苯基氯化四氮唑染色确定梗死面积。在接受组胺前体L-组氨酸治疗的大鼠中，评估了缺血后给予H(3)拮抗剂硫代哌啶和组胺-N-甲基转移酶抑制剂美托丙嗪的效果。此外，通过微透析程序研究了这些药物对纹状体组胺水平变化的影响。单独用L-组氨酸（1000mg/kg）治疗的大鼠中，局灶性缺血引起了明显的损伤。将L-组氨酸（1000mg/kg）与硫代哌啶（5mg/kg）或美托丙嗪（10mg/kg）联合给药可减轻脑梗死。脑梗死面积分别为仅用L-组氨酸治疗动物的27%和10%。硫代哌啶和美托丙嗪联合治疗可减小给予L-组氨酸（500mg/kg）大鼠的脑梗死面积，尽管在没有L-组氨酸时保护作用不明显。在组氨酸加美托丙嗪组中观察到组胺浓度显著升高，2-3小时后该值为注射生理盐水组的363%。组氨酸组和组氨酸加硫代哌啶组中的组胺浓度分别为188%和248%。这些发现表明中枢组胺能活性的增强可减少脑梗死。
