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溶血磷脂酸对β-淀粉样蛋白片段AβP31-35所致小鼠大脑皮层离体神经元凋亡的神经保护作用

郑肇青, 方羡君, 张宇, 乔健天

山西医科大学神经生物学研究室. 山西, 太原 030001；弗吉尼亚Commonwealth大学生物化学系. Richmond, VA 23298, 美国

摘要

已报道低浓度溶血磷脂酸(lysophosphatidic acid,LPA)对去血清培养所致的神经元凋亡有神经保护作用.为了进一步观察LPA是否对β-amyloid peptide fragment 31-35(AβP31-35)所致的神经元凋亡也起类似的作用,本研究应用DNA电泳分析、HO33342和TUNEL染色法等技术,对培养的小鼠大脑皮层神经元进行了观察.结果显示,只有使用较低浓度的LPA(1～10μmol/L)、并且将此剂量的LPA比AβP31-35提前12～24 h加入培养液时,才可看到LPA明显削弱了AβP31-35所致的神经元凋亡.以上结果表明,适当浓度的LPA在长时间预作用的条件下,可对AβP31-35所致的皮层神经元凋亡起保护因子或抗凋亡因子的作用,但其作用途径可能较在去血清培养所致的凋亡时更为复杂,因为在去血清的同时加入LPA就能制止去血清所致的凋亡。

关键词： 皮层神经元; 凋亡; β-淀粉样蛋白31-35; 溶血磷脂酸; 神经保护作用; 小鼠

Neuroprotective effect of lysophosphatidic acid on A#beta#P31-35-induced apoptosis in cultured cortical neurons

Zheng Zhaoqing, Fang Xianjun, Zhang Yu, Qiao Jiantian

Department of Neurobiology, Shanxi Medical University. Taiyuan 030001, Shanxi, China；Virginia Commonwealth University, Department of Biochemistry. Richmond, VA 23298, USA

Abstract

It has been reported that lysophosphatidic acid (LPA) at its lower concentrations prevents apoptosis induced by serumdeprivation in cultured cortical neurons when LPA is added into the cultural medium with serum withdrawal. The present study was designed to investigate whether LPA could also block the apoptosis induced by #beta#-amyloid peptide fragment 31-35 (AβP31-35) in cultured cortical neurons by using techniques of DNA fragmentation electrophoresis, HO33342 staining, and TUNEL examinations. The results showed that pretreatment of LPA suppressed the A#beta#P31-35-induced apoptosis only when LPA was applied to the cultured neurons with lower concentrations (1～10 #mu#mol/L) and especially, with a preceding time of 12～24 h before the A#beta#P31-35 exposure. These facts imply that LPA also acts as a neuroprotective factor against A#beta#P31-35-induced apoptosis, though the mechanism underlying the protective action in this case may be more complex than that involved in the serum deprivation-induced apoptosis.

Key words: Cultured cortical neurons;Apoptosis;#beta#-amyloid peptide fragment 31-35;Lysophosphatidic acid;Neuroprotective effect;Mice

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引用本文：

郑肇青, 方羡君, 张宇, 乔健天. 溶血磷脂酸对β-淀粉样蛋白片段AβP31-35所致小鼠大脑皮层离体神经元凋亡的神经保护作用[J]. 生理学报 2005; 57 (3): .

Zheng Zhaoqing, Fang Xianjun, Zhang Yu, Qiao Jiantian. Neuroprotective effect of lysophosphatidic acid on A#beta#P31-35-induced apoptosis in cultured cortical neurons. Acta Physiol Sin 2005; 57 (3): (in Chinese with English abstract).