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代谢型谷氨酸受体阻断剂#alpha#methyl- (4 tetrazolyl phenyl)glycine 对大鼠海马脑缺血耐受诱导的影响

冯荣芳, 李文斌, 刘惠卿, 李清君, 陈晓玲, 周爱民, 赵红岗, 艾洁

河北医科大学基础医学研究所病理生理学研究室，石家庄 50017

摘要

实验采用大鼠四血管闭塞全脑缺血模型，用硫荃染色法和胶质纤维酸性蛋白(GFAP)免疫组化法，观察右侧脑室内注射II型代谢型谷氨酸受体(metabotropic glutamate receptor 2/3 , mauR2/ 3)阻断剂，methyl-( 4-tetrazolylphenyl) glycine ( MTPG)对海马CAI区神经元缺血耐受(BIT)诱导的影响，以探讨m(iuR2/ 3在BIT诱导中的作用。54只
大鼠椎动脉凝闭后分为5组:(1)假手术组(。一8):游离双侧颈总动脉，但不夹闭;(2)单纯缺血组(。一8):夹闭双侧颈总动脉8 min; (3)缺血预处理组(。一8):夹闭双侧颈总动脉3 min作为脑缺血预处理(CIP)，再灌注24 h后再行夹闭8 min; (4) MTPG+缺血预处理组(。一22):CIP前20 min右侧脑室注射MTPG，其余步骤同缺血预处理组;MTPG的剂量分.0.2.0.04和。.008 mg，以观察其剂量效应关系;(5) MTPG+单纯缺血组(。一8):右侧脑室注射MTPG
0. 2 mg 24 h后，夹闭双侧颈总动脉8 min。所有动物均在手术后或末次缺血后7d处死，取材观察。结果如下:(1)与假手术组相比，单纯8 min缺血组海马CAI区组织学分级升高、锥体神经元密度降低，GFAP阳性表达增加(P<0. 05);(2)缺血预处理组的组织学分级、神经元密度及GFAP表达与假手术组相似，未见单纯缺血组的上述变化，表明CIP可防止后续8 min缺血造成的神经元损伤;(3) MTPG+缺血预处理组海马CAI区组织学分级明显增加、锥体神
经元密度降低，并且GFAP表达也明显增加(P<0.05)，这种变化与MTPG的剂量呈明显正相关，表明CIP对神经元的保护作用可被MTP G阻断;(4) MTPG+单纯缺血组海马CAI区组织学分级和神经元密度以及GFAP的表达与单纯缺血组相似。上述结果提示，3 min CIP可诱导BIT的形成，MTP G可阻断CIP诱导BIT的作用，表明mauR2/3参与BIT的诱导。

关键词： 脑预缺血处理; 代谢型谷氨酸受体; 甲基一(4-四唑基一苯)甘氨酸; 脑缺血耐受; 海马

Effects of #alpha# methyl (4- tetrazolyl phenyl)glycine on the induction of hippocampal ischemic tolerance in the rat

FENG Rong- Fang, LI Wen-Bin, LIU Hui- Qing, LI qing- Jun, CHEN Xiao- Ling, ZHOU Ai- Min，Zhao Honggang, Ai jie, Ai Jie

Department of Pathophysiology，Institute of Basic Medicine，Hebei Midical Universiity，Shijiazhuang 050017

Abstract

To explore the role of metabotropic glutamate receptor 2/ 3(mG1uR 2/ 3) in the induction of brain ischemic tolerance(BIT)，the influences of mG1uR2/ 3 antagonist a methyl-(4- tetrazolyl- phenyl)glycine (MTPG) on the induction of BIT and expression of glial fibrillaiy acidic protein(GFAP) in the hippocampus were observed using thionin staining and GFAP immunohistochemical staining in a rat brain ischemic model with four vessel occlusion(4 VO) .Fifty-four rats，of which bilateral vertebral arteries were occluded permanently by
electrocauteiy，were divided into 5 groups:(1)sham operated group(n一8):the bilateral carotid common arteries(BCCA) were separated，but the blood flow was not blocked;(2) ische mia group(n一8):the blood flow of BCCA was blocked for 8 min;(3) ischemic preconditioning(IP) group(n一8):the blood flow of BCCA was
occluded for 3 min as a cerebral ischemic preconditioning(CIP)，and then the rats were exposed to an 8- min brain ischemic insult 24 h after the CIP;(4) MTPG+IP group(n一22):MTPG was administered 20 min before the CIP，then the rats were exposed to an 8- min brain ischemia insult 24 h after the CIP .In order to examine dosage dependency in the effect of MTPG，4 dosages of MTPG(0.4，0.2，0. 04 and 0. 008 mg) were administered.

Key words: cerebral ischemic preconditioning;metabotropic glutamate receptors;a methyl-(4- tetrazolyl- phenyl) glycine;hippoca mpus ;

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引用本文：

冯荣芳, 李文斌, 刘惠卿, 李清君, 陈晓玲, 周爱民, 赵红岗, 艾洁. 代谢型谷氨酸受体阻断剂#alpha#methyl- (4 tetrazolyl phenyl)glycine 对大鼠海马脑缺血耐受诱导的影响[J]. 生理学报 2003; 55 (3): .

FENG Rong- Fang, LI Wen-Bin, LIU Hui- Qing, LI qing- Jun, CHEN Xiao- Ling, ZHOU Ai- Min，Zhao Honggang, Ai jie, Ai Jie. Effects of #alpha# methyl (4- tetrazolyl phenyl)glycine on the induction of hippocampal ischemic tolerance in the rat. Acta Physiol Sin 2003; 55 (3): (in Chinese with English abstract).