脱氢表雄酮唾液酸苷对Aβ_(25-35)致海马神经元损伤作用研究

Study on Effect of Dehydroepiandrosterone Derivative on A β_(25-35) induced Damages of Hippocampal Neurons in Vitro

目的 :应用原代培养胎鼠海马神经元 ,观察脱氢表雄酮唾液酸苷对 β 淀粉样蛋白 (Aβ2 5-3 5)损伤海马神经元的保护作用。方法 :海马神经元分别与Aβ2 5-3 5(0 .1μM )、脱氢表雄酮硫酸酯及脱氢表雄酮唾液酸苷孵育 2 4h后 ,检测细胞内漏出的乳酸脱氢酶 (LDH)、谷胱甘肽过氧化酶 (GSH Px)活性、脂质过氧化物 (MDA)含量及细胞存活率的变化。结果 :海马神经元与Aβ2 5-3 5共同孵育 2 4h后 ,细胞存活率显著下降、GSH Px活性降低、LDH和MDA含量升高 ;海马神经元与不同浓度脱氢表雄酮硫酸酯和脱氢表雄酮唾液酸苷共孵 2 4h后 ,能改变Aβ2 5-3 5引起的损伤 ,使细胞存活率显著升高、GSH Px活性升高、LDH活力和MDA含量降低。唾液酸苷衍生物在对部分指标的影响上 ,效价高于相应的硫酸酯。结论 :脱氢表雄酮唾液酸苷可对抗Aβ2 5-3 5所造成的神经元损伤 ,作用可能是通过清除氧自由基、抗脂质过氧化作用和提高神经元产生抗氧化能力实现的。

Objective: To study the protecting effects of dehydroepiandrosterone derivative on cultured hippocampal neurons injuried by A β 25-35, dehydroepiandrosterone sulfate was used as control.Method: After hippocampal neurons were incubated with A β 25-35 ( 0.1 μM), dehydroepiandrosterone sulfate, and dehydroepiandrosterone derivative for 24 h, respectively, the neurons surviving rate, lactate dehydrogenase (LDH), glutathione peroxidase(GSH-P X), and the contents of malondialdehyde(MDA) were measured.Result: When hippocampal neurons were incubated with A β 25-35 24 h, the neurons surviving rate descrease remarkably, GSH-Px activity was decreased, the contents of LDH and MDA were increased. After dehydroepiandrosterone derivative and dehydroepiandrosterone sulfate were used to incubate for 24 h, the surviving rate of hippocampal neurons was increased, the activity of GSH-Px was increased, LDH activity and MNA content were decreased compared with A β 25-35 group. Conclusion: These results suggested that dehydroepiandrosterone derivative may protected hippocampal neurons against damages induced by A β 25-35, and the protective effect of dehydroepiandrosterone derivative may be due to anti-lipid peroxidation via free-radical scavenging activity.