苯氧茚酮类乙酰胆碱酯酶抑制剂YKY-7对β淀粉样蛋白诱导的神经细胞损伤的保护作用  

Neuroprotective effect of 2-phenoxy-indan-1-one derivatives YKY-7,a novel acetylcholinesterase inhibitor,on β-amyloid peptide induced damage in vitro

作　　者：郑晓亮[1] 程丽艳[1] 屠凌岚[1] 颜冬梅[1] 史红[1] 

机构地区：[1]浙江省医学科学院药物研究所,浙江杭州310013

出　　处：《中国药理学通报》2010年第10期1344-1349,共6页Chinese Pharmacological Bulletin

基　　金：浙江省医药卫生科技重点计划资助项目(No2004ZD001)

摘　　要：目的观察苯氧茚酮类乙酰胆碱酯酶抑制剂YKY-7对β淀粉样蛋白25-35(β-amyloid peptide25-35,Aβ25-35)诱导的神经细胞损伤的保护作用及机制。方法以Aβ25-35诱导原代培养的大鼠皮层神经元和人神经母细胞瘤SK-N-SH细胞损伤模型,光学显微镜下观察细胞形态学以及MTT法检测YKY-7及多奈哌齐(donepezil)对损伤模型中神经细胞活率的影响,荧光显微镜、透射电镜、流式细胞仪检测YKY-7对Aβ25-35诱导的神经细胞病理性凋亡过程的影响,MTT法检测PI3K-Akt阻断剂LY294002对YKY-7神经细胞损伤保护作用的影响。结果 12.5μmol·L-1YKY-7可提高经Aβ25-35处理的大鼠皮层神经元和SK-N-SH细胞活率,且该保护作用强于相同浓度donepezil;12.5μmol·L-1YKY-7可减弱Aβ25-35诱导的SK-N-SH细胞凋亡损伤;LY294002可阻断YKY-7对Aβ25-35诱导的SK-N-SH细胞损伤的保护作用。结论苯氧茚酮类乙酰胆碱酯酶抑制剂YKY-7对Aβ25-35诱导的神经细胞凋亡具有一定的保护作用,该作用可能是通过PI3K-Akt信号通路调控。Aim To explore the neuroprotective effect and the possible mechanism of 2-phenoxy-indan-1-one derivative YKY-7,a novel acetylcholinesterase inhibitor,onβ-amyloid peptide induced damage in primary rat cortical neurons and human neuroblastoma cell lines SK-N-SH in vitro.Methods Rat cortical neurons or SK-N-SH cells were exposured to YKY-7 or Donepezil for 2 h before addition of Aβ25-35 for 48 h and then cell morphology change and cell viability were examined by light microscopy and MTT assay respectively,and SKN-SH cells apoptosis were measured by fluorescence microscopy,transmission electron microscopy and flow cytometric analysis.The interference of PI3K-Akt blocker LY294002 on the neuroprotective effect of YKY-7 was detected by MTT assay.Results Rat cortical neurons and SK-N-SH cells viability were increased by 12.5μmol·L -1 of YKY-7 after Aβ25-35 treatment,and its protective effect was stronger than the same concentration of Donepezil;SK-N-SH cells apoptosis induced by Aβ25-35 was attenuated by 12.5μmol·L -1 of YKY-7;the neuroprotective effect of YKY-7 was blocked by LY294002.Conclusion 2-phenoxy-indan1-one derivative YKY-7,an acetylcholinesterase inhibitor,has the protective effect on Aβ 25-35 induced neurons apoptosis which might be achieved through PI3KAkt signaling pathway in vitro.

关 键 词：乙酰胆碱酯酶抑制剂 原代培养大鼠神经元 人神经母细胞瘤SK-N-SH细胞 Β淀粉样蛋白 细胞凋亡 PI3K-AKT信号通路 

分 类 号：R-332[医药卫生] R329.25