Humanin通过JNK途径减轻Aβ_(31-35)诱导的皮层神经元的凋亡  

Humanin inhibit Aβ_(31-35)-induced neuronal apoptosis by JNK pathway

作　　者：李灵敏[1] 乔建天[2] 张策[2] 

机构地区：[1]山西医科大学病理学教研室,太原030001 [2]山西医科大学生理学教研室,太原030001

出　　处：《山西医科大学学报》2009年第10期871-873,F0003,共4页Journal of Shanxi Medical University

摘　　要：目的研究JNK信号通路在Aβ31-35诱导神经元凋亡中的作用以及Humanin(HN)的神经保护机制。方法原代培养大鼠皮层神经元随机分为对照组、Aβ31-35组(1h,4h,8h,16h,24h)、抑制剂SP600125组、HN预处理组。应用流式细胞术观察各组神经元凋亡率,应用免疫细胞化学法观察各组磷酸化c-Jun(p-c-Jun)和FasL蛋白表达情况。结果对照组仅有少数神经元发生凋亡;Aβ31-35诱导培养皮层神经元异常凋亡;JNK抑制剂SP600125抑制了Aβ31-35诱导的神经元凋亡;HN(20μmol/L)16h预孵育部分抑制了Aβ31-35的致凋亡作用,各组神经元凋亡率分别为7.43%,32.6%(24h),8.8%,20.36%。对照组仅有少量p-c-Jun及FasL蛋白的表达;Aβ31-35时间依赖性诱导了p-c-Jun、FasL蛋白的表达;SP600125抑制了Aβ31-35诱导的p-c-Jun、FasL蛋白的表达;20μmol/LHN16h预孵育部分抑制了p-c-Jun及FasL蛋白的表达。结论JNK通路可能参与了Aβ31-35诱导的神经元凋亡过程;HN可在一定程度上阻抑JNK信号通路,减轻Aβ31-35诱导的神经元凋亡。Objective To explore the effect of the JNK signaling pathway on Aβ31-35-induced neuronal apoptosis and neuroprotection mechanism of Humanin（HN）. Methods Primary cortical neurons were divided into four groups：control group, Aβ31-35 group, JNK inhibitor group,HN ＋ Aβ31-35 group. In Aβ31-35 group,cells were exposed to Aβ31-35 （25 μmol/L） for 1 h,4 h,8 h,16 h,24 h,respectively. In JNK inhibitor group, cells were pretreated with SP600125 （100 nmol/L）30 rain and additional Aβ31-35 8 h. In HN ＋ Aβ31-35 group, ceils were pretreated with H N （20 μmol/L）16 h and additional Aβ31-35 8 h. Apoptotic cell numbers were observed by flow cytometric assay. The expression of phosphorylation c-Jun（p-c-Jun） and Fas ligand was assessed by immunocytochemistry. Results Following incubation with Aβ31-35 for 24 h, 32.6% of the cells underwent abnormal apoptosis, significantly higher than in the controls （7.43% ,P 〈0.05）. The rate of apeptosis decreased to 8.8% in JNK inhibitor group. HN showed a significantly protective effect on the Aβ31-35-induced apoptosis. The cell apoptosis rate was 20.36% in HN ＋Aβ31-35 group. Cortical neurons exposed to Aβ31-35 time-dependently enhanced expression of p-c-Jun and Fas ligand protein. SP600125 completely abolished the up-regulated expression of p-c-Jun and Fas ligand protein induced by Aβ31-35. HN partly inhibited the expression of p-c-Jun and FasL induced by Aβ31-35. Conclusion JNK signaling pathway may mediate the Aβ31-35-induced neuronal apoptosis. Humanin inhibit Aβ31-35-induced neuronal apoptosis by JNK pathway.

关 键 词：HUMANIN Aβ31-35 JNK 神经保护 

分 类 号：R363[医药卫生—病理学]