钙调神经磷酸酶对阿尔茨海默病大鼠模型海马区PSD-95及Homer、Shank基因各亚型表达的影响  

Effect of Calcineurin on the expression of PSD-95 and Homer、Shank gene subtypes in hippocampus region of rats with Alzheimer's disease

作　　者：刘倩倩[1] 石胜良[1] 高怀清[1] 王成志[1] 郑明华[1] 

机构地区：[1]广西医科大学第一附属医院神经内科,广西南宁530021

出　　处：《中风与神经疾病杂志》2014年第11期982-985,共4页Journal of Apoplexy and Nervous Diseases

基　　金：广西壮族自治区卫生厅重点科研课题(重2012066)

摘　　要：目的探讨钙调神经磷酸酶(Calcineurin,Ca N)对阿尔茨海默病(Alzheimer’s disease,AD)大鼠模型海马区PSD-95及Homer、Shank基因各亚型表达的影响及其作用机制。方法采用Aβ1-42海马注射建立AD大鼠模型,并用他克莫司(FK506)干预,以Morris水迷宫检测大鼠的空间学习记忆能力,并用实时定量PCR(RealTime PCR)检测大鼠海马区PSD-95及Homer、Shank各亚型的mRNA表达情况。结果与对照组相比,模型组大鼠学习记忆能力明显减退(P<0.01),PSD-95、Homer1b、Shank1、Shank3的mRNA表达均下调,而Homer1a的mRNA表达上调(P<0.05)。FK506干预后,与模型组比较,学习记忆能力显著改善(P<0.01),同时PSD-95、Homer1b、Shank1、Shank3的mRNA表达均上调(P<0.05),而Homer1a的mRNA表达下调(P<0.01)。Shank2的mRNA表达在三组中均未见显著性差异(P>0.05)。结论抑制Ca N激活可明显增高海马区突触相关蛋白在基因的表达水平,从而影响突触的功能和可塑性,这可能是其改善AD症状的作用机制之一。Objective To explore the effect of Calcineurin on the expression of PSD-95 and Homer,Shank gene subtypes in hippocampus region of rats with Alzheimer＇ s disease （AD）. Methods Rats models of Alzheimer＇ s disease were established by direct β-amyloid protein （Aβ1-42） injection method. For FK506 intervention, the learning and memory ability was observed. The gene expression of PSD-95 and Homer,Shank gene subtypes in hippocampus region were analyzed by semiquantitative RT-PCR. Results Compared to control group, the learning and memory ability were obviously decreased in AD model rats （P 〈 0.01 ） , and the gene expression of PSD-95 ,Homerl b,Shankl ,Shank3 were reduced, the expression of Homerl a was raised （P 〈 0.05 ）. Compared to AD model rats, after FK506 treatment, the learning and memory ability were improved （ P 〈 0.01 ）, and the gene expression of PSD-95, Homerl b, Shankl, Shank3 were raised （ P 〈 0.05 ）, but the expression of Homerl a was lowered （ P 〈 0.01 ）. The mRNA expression of Shank2 had no significant difference between the three groups. Conclusion Inhibiting Calcineurin can obviously heighten the synaptic related proteins in gene expression levels, which affects axonal function and plasticity, this may be one of its mechanisms in improving symptoms of AD.

关 键 词：阿尔茨海默病 钙调神经磷酸酶 HOMER SHANK PSD-95 

分 类 号：R749.16[医药卫生—神经病学与精神病学]