摘要
目的:谷氨酸浓度过度升高和谷氨酸受体过度活化引起的兴奋毒性是缺氧缺血性脑损伤hypoxic-ischemicbraindamage,HIBD发生发展的重()要环节,α-氨基-3-羟基-5-甲基异恶唑-4-丙酸(alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionicacid,AMPA型谷氨)酸受体起重要作用。研究选择性AMPA受体拮抗剂GYKI-52466对新生鼠HIBD的保护作用及机制。方法:实验于2003-04/2004-03在解放军第三军医大学新桥医院中心实验室完成。7日龄Wistar大鼠27只,随机分为4组:正常对照组;假手术组;缺氧缺血组;GYKI-52466干预组。正常对照组用于观察脑组织髓鞘碱性蛋白(myelinbasicprotein,MBP)在正常新生鼠的表达情况;干预组在缺氧缺血后即刻开始予GYKI-5246610mg/kg腹腔注射,1次/h,共4次;假手术组予等量生理盐水腹腔注射。缺血缺氧后1周取脑,免疫组化、图像分析法测双侧脑半球横截面积之比,检测脑组织MBP、NF表达及积分吸光度值。结果:缺血缺氧后患侧脑组织横截面积下降。缺血缺氧后1周,缺氧缺血()(组患侧与对侧脑半球横截面积之比L:RAREA为0.680±0.043),较假手术组(0.985±0.023)明显降低(P<0.001);GYKI-52466干预组L:RAREA值为0.804±0.031),明显高于缺氧缺血组(P<0.001)。MBP(第8天无显著表达。生后第11天嗅束、纹状体、胼胝?
AIM: Exitotoxicity caused by over increase of glutamic acid concentration and the over activation of its receptor are the key links for the occurrence and development of hypoxic ischemic brain damage (HIBD), and the glutamic acid receptor of alpha amino 3 hydroxy 5 methyl 4 isoxazolepropionic acid (AMPA) type plays an important role. This paper aims to determine the protective effect of selective AMPA receptor antagonist GYKI 52466 on HIBD in neonatal rats and investigate its mechanism.METHODS: The experiment was done in the Central Laboratory of Xinqiao Hospital, Third Military Medical University of Chinese PLA from April 2003 to March 2004. Twenty seven 7 day old Wistar rats were randomly divided into normal control group, sham operated group, HIBD group and GYKI 52466 intervention group.Expression of myelin basic protein (MBP) was observed in the normal control group, rats in the GYKT 52466intervention group received intraperitoneal injection of GYKI 52466 (10 mg/kg, once an hour for 4 times) immediately after hypoxia ischemia (HI), while those in the sham operated group were treated with intraperitoneal injection of saline of the same volume. Brain tissues were taken one week after HI, immunohistochemistry and image analysis were performed to determine the cross section area ratio of bilateral cerebral hemispheres, and detecte the expression of MBP and the integral absorbance (A). RESULTS: The cross section area of the damaged side of brain tissue after hypoxia ischemia was decreased. One week after HI, the ratio of left to right hemispheric cross sectional area (L:R AREA) in the HIBD group (0.680 ± 0.043) was obviously decreased as compared with that in the sham operated group (0.985± 0.023) (P< 0.001), and it was significantly higher in the GYKI 52466 intervention group (0.804± 0.031) than in the HIBD group (P< 0.001).There was insignificant MBP expression on the 8th day. On the 11th day, positive olfactory tract, corpus striatum, corpus callosum, external
出处
《中国临床康复》
CSCD
北大核心
2005年第11期173-175,共3页
Chinese Journal of Clinical Rehabilitation
