他克莫司对皮层神经元β-淀粉样蛋白生成及突触蛋白表达的影响  

Effect of FK506 on release of β-amyloid protein and expression of synaptophysin in cortical neurons

作　　者：梅峥嵘[1] 司徒冰[1] 曾晓敏[1] 王颖[1] MEI Zheng-rong SI-TU Bing ZENG Xiao-min WANG Ying(Department of Pharmacy, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150)

机构地区：[1]广州医科大学附属第三医院药学部,广州510150

出　　处：《中南药学》2016年第11期1194-1197,共4页Central South Pharmacy

基　　金：广州市教育局基金资助项目(NF-κB和NFAT1的crosstalk激活BACE1表达的体外研究)(No.1201421151)

摘　　要：目的阿尔茨海默病(AD)的主要病理机制是β-淀粉样蛋白(Aβ)的聚集,本实验利用大鼠皮层神经元研究钙调磷酸酶抑制剂他克莫司(FK506)对Aβ产生的影响及可能的机制。方法体外培养大鼠皮层神经元,过表达突变型APP基因,将细胞分为4组,分别为对照组,FK506低剂量、中剂量及高剂量组。MTT法检测细胞活力;ELISA检测细胞分泌Aβ40及Aβ42水平;Western blot及实时荧光定量PCR检测β-分泌酶(BACE1)和synaptophysin的蛋白及基因表达。结果与模型组比较,FK506显著降低Aβ40及Aβ42水平、下调BACE1的表达并上调synaptophysin的表达。结论 FK506可减少大鼠皮层神经元分泌Aβ,阻止突触的丢失,其作用机制可能与抑制BACE1表达有关。Objective To investigate the effect of FK506 on the release of β-amyloid protein（Aβ）, the hallmark of Alzheimer＇s disease（AD） being the accumulation of Aβ in cortical neurons overexpressing mutant human APP, and explore the potential mechanism. Methods Primary neuron cells were cultured and transfected mutant APP gene. Primary neuron cells expressing APP were divided into 4 groups： a control and 3 FK506 dose groups. The cell viability was assessed by MTT; the levels of Aβ40 and Aβ42 were measured by ELISA; gene and protein expression of BACE1 and synaptophysin were analyzed by real time PCR or Western blot. Results Compared with the control group, FK506 significantly reduced the release of Aβ40 and Aβ42, decreased the expression of BACE1, and upregulated the expression of synaptophysin. Conclusion FK506 may decrease Aβ levels and protect synapse against overexpressing APP gene. Its neuronprotection may be related to the inhibition of BACE1 expression.

关 键 词：阿尔茨海默病 Β-淀粉样蛋白 他克莫司 突触蛋白 

分 类 号：R749.16[医药卫生—神经病学与精神病学]