大鼠侧脑室注射δ-阿片受体拮抗剂naltrindole或激动.doc

生理学报 Acta Physiologica Sinica, August 25, 2008, 60 (4): 475-484 475 研究论文 大鼠侧脑室注射δ-阿片受体拮抗剂naltrindole或激动剂TAN-67对急性脑缺血的影响 田雪松1，周 飞1, 2，杨 茹1，夏 萤2, 3，吴根诚1，郭景春1,* 1复旦大学上海医学院医学神经生物学国家重点实验室，中西医结合系，上海200032；2上海市针灸经络研究中心，上海201203；3美国耶鲁大学医学院，纽海文CT 06520 摘 要：本文旨在探讨δ-阿片受体(δ-opioid receptor, DOR)在急性脑缺血/再灌注损伤中的作用。除假手术组外，其余各组均用大脑中动脉线栓法(middle cerebral artery occlusion, MCAO)制备大鼠右侧局灶性缺血/再灌注模型，缺血1 h再灌注24 h。于缺血前30 min侧脑室分别注射DOR拮抗剂naltrindole (20 nmol, 50 nmol, 100 nmol)、激动剂TAN-67 (30 nmol, 60nmol, 200 nmol)或人工脑脊液，用Longa 5 分制评分标准对大鼠进行神经功能评分，焦油紫(cresyl violet, CV)染色和图像分析处理系统测量梗死灶大小，Western blot 检测纹状体DOR蛋白的表达。结果表明，60 nmol TAN-67显著减小梗死体积(P<0.05)，提高神经功能缺损评分(P<0.05)，约60 kDa 的DOR蛋白表达也倾向于上升(P>0.05)；100 nmol 的naltrindole加重脑缺血损伤，约60 kDa的DOR蛋白表达下降 (P<0.05)。上述结果提示，激动DOR对急性缺血/再灌注大鼠的脑损伤有保护作用，而阻断DOR则加重其损伤。 关键词：脑缺血；δ-阿片受体；TAN-67；naltrindole；大脑中动脉栓塞 中图分类号：R743.3 Effects of intracerebroventricular injection of δ-opioid receptor agonist TAN-67or antagonist naltrindole on acute cerebral ischemia in rat TIAN Xue-Song1, ZHOU Fei1,2, YANG Ru1, XIA Ying2,3, WU Gen-Cheng1, GUO Jing-Chun1,* 1National Key Laboratory of Medical Neurobiology, Department of Integrative Medicine, Shanghai Medical College, FudanYale University School of Medicine, New Haven, CT 06520, USAUniversity, Shanghai 200032, China; 2Shanghai Research Center for Acumoxibustion and Meridians, Shanghai 201203, China;3 Abstract: This work was performed to determine the role of δ-opioid receptor (DOR) in protection against acute ischemia/reperfusioninjury. Transient (1 h) focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). DOR agonist TAN-67 (30nmol, 60 nmol, 200 nmol), DOR antagonist naltrindole (20 nmol, 50 nmol, 100 nmol) or artificial cerebral spinal fluid (aCSF) wasinjected respectively into the lateral cerebroventricle of the rat 30 min before the induction of brain ischemia. Neurological deficits were assessedby the five-grade system (Longa’s methods). The brain infarct was measured by cresyl violet (CV) stainin