QUANTITATIVE-ANALYSIS OF EFFECTS OF KAPPA-OPIOID AGONISTS ON POSTISCHEMIC HIPPOCAMPAL CA-1 NEURONAL NECROSIS IN GERBILS
QUANTITATIVE-ANALYSIS OF EFFECTS OF KAPPA-OPIOID AGONISTS ON POSTISCHEMIC HIPPOCAMPAL CA-1 NEURONAL NECROSIS IN GERBILS
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DOI：
10.1161/01.str.19.8.1008
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发表时间：
1988-08-01
期刊：
影响因子：
8.3
通讯作者：
PAZARA, KE
中科院分区：
文献类型：
--
作者：
HALL, ED;PAZARA, KE
卡帕的能力。-阿片受体激动剂U50488H和U62066E（甲磺酸螺旋喹啉）与非。研究了结构类似物U54494A对雄性蒙古沙鼠选择性易损海马CA1神经元缺血后坏死的影响。沙鼠在轻度甲氧基氟醚麻醉下双侧颈动脉闭塞或假性闭塞10分钟前30分钟和后2小时分别用生理盐水溶液或其中一种试验药物10 mg/kg。缺血再灌注7 d后，进行脑灌注固定，盲法计数海马CA1细胞。在缺血沙鼠中，与假闭塞沙鼠相比，仅接受载药的沙鼠CA1神经元损失78.9%。相比之下，u50488h处理组沙鼠的平均细胞损失率降至33.9% （p < 0.01）。U62066E在减少缺血后CA1变性方面更有效，仅为20.7%（与载药组相比p < 0.001）。然而，用非。kappa处理。模拟物U54494A不产生任何明显的保护；这组沙鼠的CA1神经元丢失了80.7%。我们的结果与。kappa。-受体刺激与改善脑缺血后神经元保存有关。
The ability of the .kappa.-opioid receptor agonists U50488H and U62066E (spiradoline mesylate) compared with the non-.kappa. close structural analogue U54494A to affect postischemic necrosis of the selectively vulnerable hippocampal CA1 neurons was examined in male Mongolian gerbils. The gerbils were treated with either saline vehicle or 10 mg/kg i.p. of one of the test drugs 30 minutes before and again 2 hours after a 10-minute period of bilateral carotid artery occlusion or sham occlusion under light methoxyflurane anesthesia. Seven days after ischemia and reperfusion the brains were perfusion-fixed and hippocampal CA1 cells were counted in a blind fashion. In ischemic gerbils that received only vehicle, there was a 78.9% loss of CA1 neurons compared with sham-occluded gerbils. In contrast, in U50488H-treated gerbils, mean cell loss was reduced to 33.9% (p < 0.01 vs. vehicle-treated group). U62066E was even more effective in reducing postischemic CA1 degeneration to only 20.7% (p < 0.001 vs. vehicle-treated group). However, treatment with the non-.kappa. analogue U54494A did not cause any apparent protection; the gerbils in this group showed an 80.7% loss of CA1 neurons. Our results are consistent with the hypothesis that .kappa.-receptor stimulation is associated with improved postischemic neuronal preservation.