阿魏酸钠通过ERK和PI3K信号传导通路对抗淀粉样β蛋白片段1-42引起的海马神经元凋亡  

Sodium ferulate inhibits Aβ_(1-42)-mediated hippocampal neuronal apoptosis through activation of ERK and PI3K signaling pathways

作　　者：闫恩志[1] 范莹[1] 隋海娟[1] 刘婉珠[2] 金英[1] 

机构地区：[1]辽宁医学院,药理学教研室,辽宁锦州121001 [2]辽宁医学院,机能实验中心,辽宁锦州121001

出　　处：《中成药》2013年第5期880-884,共5页Chinese Traditional Patent Medicine

基　　金：辽宁省教育厅科学研究项目(L2012310);辽宁省教育厅创新团队项目(LT 2010064)

摘　　要：目的研究阿魏酸钠对β蛋白片段1-42(Aβ1-42)引起培养海马神经元损伤的保护作用的信号传导机制。方法原代培养SD大鼠海马神经元,阿魏酸钠(100,200μmol/L)预处理6 h后,加入50 nmol/L的Aβ1-42作用72 h,MEK阻断剂PD98059(10μmol/L)、Akt阻断剂tricribine(1μmol/L)分别在加入阿魏酸钠前30 min加入,Ho-echst33258细胞核荧光染色观察细胞凋亡变化,Western蛋白印迹法检测海马神经元磷酸化的MEK1、ERK1/2、CREB、Akt/PKB、p70s6K、GSK-3β蛋白表达。结果与对照组相比,经Aβ1-42损伤的海马神经元细胞凋亡率明显增加(P<0.01),相应磷酸化的MEK1、ERK1/2、CREB、Akt、p70s6K、GSK-3β蛋白表达水平明显降低(P<0.01)。应用阿魏酸钠预处理可明显拮抗Aβ1-42引起的海马神经元细胞凋亡和磷酸化蛋白表达水平的降低(P<0.01),但阿魏酸钠的作用可被PD98059、tricribine所抑制。结论阿魏酸钠可通过激活Akt/p70S6K、Akt/GSK-3β和MEK/ERK信号传导通路对抗Aβ1-42引起的海马神经元损伤。AIM To investigate the protective effect and mechanism of sodium ferulate on neurotoxicity of cul- tured hippocampal neurons induced by beta-protein fragment 1-42 （Aβ142）. METHODS The primary culture of hippocampal neurons derived from neonatal SD rats was exposed to 50 nmol/L Aβ1.42 for 72 h after pretreatment with 100 and 200 μmol/L sodium ferulate for 6 h. 10 μmol/L PD98059 and 1 μmol/L tricribine were added re- spectively to the cells 30 min prior to sodium ferulate treatment. The morphological change of the apoptosis cells was observed by Hoechst 33258 fluorescence staining. Western blotting was used to detect the expression levels of phospho-MEK1, phospho-（ERK） 1/2, phospho-CREB, phospho-Akt, phospho-pT0s6K and phospho-GSK-3β in cellullar extracts. RESULTS Sodium ferulate increased Aβ1.42-induced apoptosis rate, and decreased expression levels of phospho-MEK1, phospho-（ERK） 1/2, phospho-CREB, phospho-Akt, phospho-p70s6K and phospho- GSK-3β protein. Protective effect of sodium ferulate against Aβ142-induced neuronal apoptosis could be blocked by PD98059 and tricribine. CONCLUSIOI Sodium ferulate can prevent the cultured hippocampal neurons from Aβ1-42 neurotoxicity by activing Akt/p70S6K, Akt/GSK-3β and MEK/ERK signaling pathways.

关 键 词：阿魏酸钠 Β淀粉样蛋白 海马神经元 细胞外信号调节激酶 蛋白激酶B 

分 类 号：R285.5[医药卫生—中药学]