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目的在脑老化和阿尔茨海默尔氏病人脑中,氧自由基的升高是其神经元发生退行性病变,从而导致突触可塑性和认知障碍的机制之一。本文研究了阿尼西坦(aniracetam,一种治疗老年痴呆的药物)对抗双氧水损伤神经元活力,线粒体电位及海马突触传递长时程增强(Long-term potentiation, LTP)的作用。方法用四甲基偶氮唑盐(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide,MTT)法测定神经元的活力,用线粒体荧光探针MitoTracker Red (CMX Ros) 研究线粒体电位的变化,用膜片钳方法记录了海马CA1区的突触传递效能。结果200 μmol/L的双氧水明显损伤小鼠大脑皮层原代培养神经元的细胞活力,降低其线粒体电位,而10 μmol/L或100 μmol/L阿尼西坦预处理能明显对抗双氧水对细胞活力和线粒体电位的降低作用。双氧水在不影响基础突触传递的剂量下(20 μmol/L),却能显著抑制海马LTP的诱导。阿尼西坦在100 μmol/L剂量下,对基础突触传递没有明显影响,对正常小鼠脑片CA1区的LTP也没有易化作用,然而,100 μmol/L的阿尼西坦却能显著地恢复由双氧水损伤的海马LTP。结论本研究结果表明,阿尼西坦对双氧水导致的毒性具有较强的神经保护作用,这为临床上用其治疗神经退行性疾病提供了参考依据。
OBJECTIVE: In the brain of Alzheimer’s disease patients, the elevation of oxygen free radicals is one of the mechanisms of degenerative neuron degeneration, leading to synaptic plasticity and cognitive impairment. This article investigates the role of aniracetam (a drug for the treatment of Alzheimer’s disease) against the neuronal activity, mitochondrial potential and hippocampal synaptic transmission of long-term potentiation (LTP) induced by hydrogen peroxide. Methods The viability of neurons was measured by MTT assay and the mitochondrial fluorescent probe MitoTracker Red (CMX Ros ) To study the change of mitochondrial potential. The synaptic transmission of hippocampal CA1 region was recorded by patch-clamp method. Results Hydrochloric acid (200 μmol / L) significantly injured the cell viability and decreased the mitochondrial potential of primary cultured neurons in mouse cerebral cortex. Pretreatment with 10 μmol / L or 100 μmol / L aniracetam significantly inhibited cell viability And mitochondrial potential reduction effect. Hydrogen peroxide did not affect the basal synaptic transmission dose (20 μmol / L), but significantly inhibited the induction of LTP in the hippocampus. Aniracetam had no significant effect on basal synaptic transmission at 100 μmol / L and no facilitation of LTP in CA1 of normal mice. However, 100 μmol / L of aniracetam Hippocampal LTPs damaged by hydrogen peroxide are significantly recovered. Conclusion The results of this study show that aniracetam has a strong neuroprotective effect on the toxicity caused by hydrogen peroxide, which provides a reference for the treatment of neurodegenerative diseases clinically.