Humanin通过内源性途径抑制Aβ_(31-35)诱导的神经元凋亡(英文)  

Humanin protects neurons against apoptosis induced by Aβ_(31-35) through suppression of intrinsic pathway

作　　者：李灵敏[1] 张宇[2] 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：《生理学报》2010年第2期93-100,共8页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China (No. 30572085);Natural Science Foundation of Shanxi Province,China (No. 2007011111)

摘　　要：为了探讨Humanin(HN)对Aβ31-35诱导的培养皮层神经元凋亡的影响,本研究采用不同浓度(5、10、20μmol/L)的HN预孵育体外培养的皮层神经元不同时间(0、8、16h),加入Aβ31-35(25μmol/L)24h后,应用电子显微镜观察神经元的凋亡情况;流式细胞术、TUNEL法检测神经元的凋亡率;酶标仪检测caspase活性;Westernblot检测Bax蛋白的表达。结果显示:HN(20μmol/L)预孵育16h明显抑制了Aβ31-35诱导的神经元凋亡;HN降低了Aβ31-35诱导的caspase-3、9活性的升高;HN抑制了Aβ31-35诱导的Bax从胞浆到线粒体的转位。以上结果提示,HN通过阻断内源性凋亡途径抑制Aβ31-35诱导的神经元凋亡。The present study aimed to investigate the effects of humanin （HN） on primary cortical neuronal apoptosis induced by Aβ31-35,and explore the potential mechanisms.Cultured cortical neurons were pretreated with different concentrations of HN （5,10,20 μmol/L） for different time period （0,8 and 16 h） respectively,and then exposed to Aβ31-35 （25 μmol/L） for additional 24 h and the neuronal apoptosis was examined by morphological analysis,flow cytometric assays and TUNEL staining.Caspase activities were measured using a spectrophotometer.Bax expression was measured by Western blot.The results were as follows.（1） Pretreatment with HN （20 μmol/L） for 16 h significantly prevented Aβ31-35-induced apoptosis in cortical neurons;（2） HN significantly decreased Aβ31-35-induced elevation of caspase-3 and -9 activities;（3） HN suppressed Aβ31-35-induced translocation of Bax from the cytosol to mitochondria,but had no effect on overall Bax expression.In conclusions,HN attenuated Aβ31-35-induced cortical neuronal apoptosis by blocking intrinsic caspase-dependent apoptotic pathways.

关 键 词：Aβ31-35 HUMANIN 凋亡 神经保护 内源性途径 

分 类 号：R33[医药卫生—人体生理学]