NVP-AAM077和Ro25-6981对全脑缺血小鼠海马神经元损伤及BDNF表达的影响  

Effect of NVP-AAM077 and Ro25-6981 on hippocampal neuronal injury and brain derived neurotrophic factor expression in global cerebral ischemic mice

作　　者：陈远寿[1] 罗孝美[1] 陈旻[2] 张弛[2] 

机构地区：[1]遵义医学院生理学教研室,贵州遵义563003 [2]中国科学院神经科学研究所神经科学国家重点实验室,上海200031

出　　处：《中国药理学通报》2010年第8期1010-1013,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30721004)

摘　　要：目的探讨N-甲基-D-天冬氨酸受体(NMDA)亚基NR2A和NR2B特异性拮抗剂对脑缺血/再灌注后海马CA1区神经元损伤的不同影响及其可能机制。方法制作三动脉阻断(3-VO)小鼠全脑缺血模型,小鼠随机分为假手术组、脑缺血/再灌注(I/R)对照组、NVP-AAM077(NVP)干预组和Ro25-6981(Ro)干预组;应用Fluoro-JadeB(F-JB)和Nissl染色检测海马神经元变性死亡和存活情况,Western blot对脑源性神经生长因子(BDNF)蛋白表达水平进行定量分析。结果①小鼠全脑缺血12min/再灌注3d后,海马CA1区出现选择性迟发性神经元死亡,NVP干预组增加了缺血所致的海马神经元死亡(P<0.05),而Ro干预组CA1区神经元存活数量明显多于缺血/再灌注组(P<0.01);②NVP干预能明显下调缺血/再灌注所致的海马组织BDNF蛋白表达升高(P<0.01),而Ro干预能明显上调BDNF蛋白的表达(P<0.05)。结论 NMDA受体亚基NR2A和NR2B在小鼠脑缺血/再灌注损伤中具有不同的作用,其机制可能与调节BDNF表达改变有关。Aim The aim of the present study is to in-vestigate the effect of the specific antagonist NVP-AAM077 and Ro25-6981 of NMDA receptor subunit NR2A and NR2B on global cerebral ischemia-induced neuronal injury in the CA1 region. Methods Male C57BL/6 mice subjected to global ischemia by the three-vessel occlusion（ 3-VO） method,were divided into four groups： sham-operated group,ischemia/reperfusion control group,NVP-AAM077 treatment group,and Ro25-6981 treatment group. Hippocampal sections were processed for Fluoro-Jade B staining to detect degenerating neurons and for Nissl staining to identify surviving neurons. The expression of brain derived neurotrophic factor（ BDNF） were measured by Western blot. Results ① Transient brain ischemia induced selective and delayed neuron death in the CA1 region of the hippocampus at 12-minute ischemia after reperfusion 3 days. NR2A subtype specific antagonist NVP-AAM077 enhanced neuronal death after transient global ischemia （ P〈0. 05） . In contrast,NR2B subtype specific antagonist Ro25-6981 attenuated ischemic cell death when compared with the ischemia/reperfusion control groups （ P〈0. 01） . ② The NR2A subtype specific antagonist NVP-AAM077 significantly attenuated ischemia-induced BDNF expression（ P〈0. 01） . In contrast,NR2B subtype specific antagonist Ro25-6981 significantly enhanced BDNF expression（ P〈0. 05） . Conclusions These results suggest that NR2A-and NR2B-containing NMDA receptor subtypes play differential roles in ischemic neuronal death; the effect might be related to regulation of BDNF expression in mouse brain.

关 键 词：NVP-AAM077 Ro25-6981 NMDA受体 脑缺血 脑源性神经营养因子 海马 

分 类 号：R-332[医药卫生] R322.81