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Humanin 通过内源性途径抑制Aβ 31-35 诱导的神经元凋亡

李灵敏, 张宇, 乔建天, 张策

山西医科大学 病理学教研室；生理学教研室，太原 030001

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、20 μmol/L)的HN 预孵育体外培养的皮层神经元不同时间(0、8、16 h)，加入Aβ31-35 (25 μmol/L) 24 h 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；Western blot 检测Bax 蛋白的表达。结果显示：HN (20 μmol/L)预孵育16 h 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。

关键词： Aβ31-35; Human in; 凋亡; 神经保护; 内源性途径

分类号：R32 9

Humanin protects neurons against apoptosis induced by Aβ31-35 through suppression of intrinsic pathway

LI Ling-Min, ZHANG Yu, QIAO Jian-Tian, ZHANG Ce

Department of Pathology； Department of Physiology, Shanxi Medical University, Taiyuan 030001, China

Abstract

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) fordifferent time period (0, 8 and 16 h) respectively, and then exposed to Aβ31-35 (25 μmol/L) for additional 24 h and the neuronalapoptosis was examined by morphological analysis, flow cytometric assays and TUNEL staining. Caspase activities were measuredusing a spectrophotometer. Bax expression was measured by Western blot. The results were as follows. (1) Pretreatment with HN (20μmol/L) for 16 h significantly prevented Aβ31-35-induced apoptosis in cortical neurons; (2) HN significantly decreased Aβ31-35-inducedelevation of caspase-3 and -9 activities; (3) HN suppressed Aβ31-35-induced translocation of Bax from the cytosol to mitochondria, buthad no effect on overall Bax expression. In conclusions, HN attenuated Aβ31-35-induced cortical neuronal apoptosis by blocking intrinsiccaspase-dependent apoptotic pathways.

Key words: Aβ31-35; humanin; apoptosis; neuroprotection; intrinsic pathways

收稿日期：2009-12-03　　录用日期：2010-01-21

通讯作者：张策　　E-mail: cezh2002@yahoo.com

引用本文：

李灵敏, 张宇, 乔建天, 张策. Humanin 通过内源性途径抑制Aβ 31-35 诱导的神经元凋亡[J]. 生理学报 2010; 62 (2): 93-100.

LI Ling-Min, ZHANG Yu, QIAO Jian-Tian, ZHANG Ce. Humanin protects neurons against apoptosis induced by Aβ31-35 through suppression of intrinsic pathway. Acta Physiol Sin 2010; 62 (2): 93-100 (in Chinese with English abstract).