代谢型谷氨酸受体1亚型选择性拮抗剂LY367385对抗大鼠缺血性脑水肿  

Alleviation of brain ischemic edema in rats by LY367385, a selective antagonist of metabotropic glutamate receptor 1

作　　者：袁芳[1] 王忠诚[1] 徐立新[1] 张亚卓[1] 

机构地区：[1]北京市神经外科研究所,100050

出　　处：《中华神经外科杂志》2006年第4期245-248,共4页Chinese Journal of Neurosurgery

基　　金：北京市科技新星计划项目(953813000)北京市自然科学基金项目(7043065)

摘　　要：目的研究代谢型谷氨酸受体1亚型(mGluR1)选择性拮抗剂LY367385对大鼠缺血性脑水肿的影响。方法 Wistar雄性大鼠(280-320g)线栓法复制大脑中动脉闭塞(MCAO)脑缺血模型。动物随机分为生理盐水(NS)对照组、LY367385给药组及MK-801给药组,于MCAO后1min, 侧脑室内注射NS或LY367385(500nmol)5μl,或腹腔注射MK-801(1mg／kg)。各组动物分别于 MCAO 6、24h进行神经病学评分、脑含水量测定及脑梗死面积测定。结果 LY367385明显改善大鼠脑缺血引起的神经症状,而MK-801在MCAO 6h增加神经病学评分。LY367385降低大鼠MCAO引起的脑含水量增加,MK-801无明显作用。LY367385及MK-801均降低脑梗死面积百分率,且 LY367385作用优于MK-801。结论 LY367385能对抗大鼠脑缺血性脑水肿,作用明显优于MK-801。Objective To study effects of LY367385 （2- methyl- 4- carboxyphenylglycine ）, a selective antagonist of metabotropic glutamate receptor 1 （ mGluR1 ）, on brain ischemic edema in rats, and compare its effects with MK- 801 （5- methy- 10, 11- dihydro- 5H- dibenzocyclohepten- 5, 10- imine maleate） , an antagonist of NMDA receptor. Methods Male Wistar rats （280 -320g） were used to induce brain ischemia by inserting a nylon thread through fight internal carotid artery to the middle cerebral artery （MCA occlusion, MCAO）. Rats were randomly divided into three groups, which were normal saline （NS） group, LY367385 group and MK- 801 group. 10 minutes after MCAO, 5μl of LY367385 or NS were microinjected into lateral ventricles respectively, and MK- 801 （lmg/kg） was administrated intraperitoneally. Scoring of neurologic deficit and measuring of brain water content and brain infarcted area were processed 6h and 24h after MCAO. Results Neurologic deficit scores of rats with MCAO were decreased by LY367385, but increased by MK- 801 at MCAO 6h. The increases of brain water content induced by MCAO were not affected by MK- 801 treatment, but attenuated by LY367385 at MCAO 24h. Red tetrazolium staining showed both LY367385 and MK- 801 reduced infarcted areas induced by MCAO, and LY367385 was more effective. Conclusions LY367385 can alleviate brain ischemic edema in rats and is more effective than MK- 801.

关 键 词：脑缺血 脑水肿 MGLUR1 NMDA受体 

分 类 号：R743.3[医药卫生—神经病学与精神病学]