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大鼠侧脑室注射#delta#--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, 周飞, 杨茹, 夏萤, 吴根诚, 郭景春

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；上海市针灸经络研究中心.上海 201203

摘要

该文旨在探讨#delta#--阿片受体(#delta#--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1h再灌注24h。于缺血前30min侧脑室分别注射DOR拮抗剂naltrindole(20nmol,50nmol,100nmol)、激动剂TAN--67(30nmol,60nmol,200nmol)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,60nmol TAN--67显著减小梗死体积({sl P}<0.05),提高神经功能缺损评分({sl P}<0.05),约60kDa的DOR蛋白表达也倾向于上升({sl P}>0.05);100nmol的naltrindole加重脑缺血损伤,约60kDa的DOR蛋白表达下降({sl 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; #delta#-阿片受体; TAN-67; naltrindole; 大脑中动脉栓塞

Effects of intracerebroventricular injection of #delta#--opioid receptor agonist TAN--67 or antagonist naltrindole on acute cerebral ischemia in rat

Tian Xuesong, Zhou Fei, Yang Ru, Xia Ying, Wu Gencheng, Guo Jingchun

National Key Laboratory of Medical Neurobiology,Department of Integrative Medicine,Shanghai Medical College,Fudan University.Shanghai 200032；China

Abstract

This work was performed to determine the role of #delta#-opioid receptor (DOR) in protection against acute ischemia/reperfusion injury. Transient (1 h) focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO). DOR agonist TAN-67 (30 nmol, 60 nmol, 200 nmol), DOR antagonist naltrindole (20 nmol, 50 nmol, 100 nmol) or artificial cerebral spinal fluid (aCSF) was injected respectively into the lateral cerebroventricle of the rat 30 min before the induction of brain ischemia. Neurological deficits were assessed by the five-grade system (Longa's methods). The brain infarct was measured by cresyl violet (CV) staining and infarct volume was analyzed by an image processing and analysis system. The expression of DOR was detected by Western blot. The results showed that 60 nmol TAN-67 significantly reduced the infarct volume (P<0.05), attenuated neurological deficits (P<0.05) and tended to increase the expression of about 60 kDa DOR protein (P>0.05), while 100 nmol naltrindole aggravated ischemic damage and decreased about 60 kDa DOR protein expression (P<0.05). These results suggest that DOR activation protects the brain against acute ischemia/reperfusion injury in rat.

Key words: brain ischemia;#delta#-opioid receptor;TAN-67;naltrindole;middle cerebral artery occlusion

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引用本文：

田雪松, 周飞, 杨茹, 夏萤, 吴根诚, 郭景春. 大鼠侧脑室注射#delta#--阿片受体拮抗剂naltrindole或激动剂TAN--67对急性脑缺血的影响[J]. 生理学报 2008; 60 (4): 475-484.

Tian Xuesong, Zhou Fei, Yang Ru, Xia Ying, Wu Gencheng, Guo Jingchun. Effects of intracerebroventricular injection of #delta#--opioid receptor agonist TAN--67 or antagonist naltrindole on acute cerebral ischemia in rat. Acta Physiol Sin 2008; 60 (4): 475-484 (in Chinese with English abstract).