美金胺对缺血性脑损伤保护作用的研究  

Pathological study on the neuroprotection of memantine against cerebral ischemia in SD rats

作　　者：王维维[1] 张光毅[1] 

机构地区：[1]徐州医学院生物化学与分子生物学研究中心,江苏徐州221002

出　　处：《徐州医学院学报》2008年第7期437-440,共4页Acta Academiae Medicinae Xuzhou

摘　　要：目的观察美金胺对SD雄性大鼠全脑缺血/再灌注后海马CA1区锥体细胞的保护作用,并研究其可能的机制。方法采用四动脉结扎法建立大鼠全脑缺血模型,缺血15min后分别灌注6h或5天。大鼠随机分为假手术组、缺血/再灌注组、缺血/再灌注给药组和缺血/再灌注溶剂对照组。缺血/再灌注给药组腹腔注射20mg/kg美金胺。使用免疫印迹、免疫沉淀和焦油紫染色法等技术检测相关信号蛋白的表达、活化水平及神经元细胞的死亡。结果大鼠缺血/再灌注5天后,缺血/再灌注给药组海马CA1区细胞的存活数量较缺血/再灌注组和缺血/再灌注溶剂对照组明显增加;缺血/再灌注6h,缺血/再灌注给药组N-甲基-D-天门冬氨酸(NMDA)受体亚基2A(NR2A)、突触后密集区蛋白95(PSD-95)、非受体型蛋白酪氨酸激酶(Src)三者间免疫沉淀的蛋白量及NR2A的酪氨酸磷酸化水平较缺血/再灌注组和缺血/再灌注溶剂对照组明显降低,而三者的表达量没有明显变化。结论美金胺通过抑制NR2A、PSD-95、Src三者结合及Src介导的NR2A的酪氨酸磷酸化抑制了缺血后NMDA受体功能的增强,从而对大鼠缺血性脑损伤有保护作用。Objective To evaluate the neuroprotection of memantine against cerebral ischemia in SD rat models,and investigate the underlying mechanism.Methods Rats were randomly assigned to 4 groups： sham-operation group,ischemia/reperfusion group,vehicle control group and drug test group.Transient brain ischemia（15 min） and reperfusion was induced by the four-vessel occlusion method（4-VO）.The experiment was performed by using IB,IP and morphologic methods to examine the expression of relevant message proteins and the survival of hippocampal neurons.Results Transient cerebral ischemia/reperfusion induced obvious neuronal death,which could be improved by the use of memantine.It was also found that memantine inhibited the interactions between NR2A,Src and PSD-95,and decreased the tyrosine phosphorylation of NR2A.Conclusions The neuroprotective effects of memantine against cerebral ischemic/reperfusion damage are pathologically confirmed in SD rats models.And the mechanism may involve the tyrosine phosphorylation of NR2A by Src.

关 键 词：脑缺血/再灌注 美金胺 NMDA受体 NR2A SRC 

分 类 号：R364.12[医药卫生—病理学]