维生素C保护Aβ1-40Cu(Ⅱ)复合物引起的神经元氧化损伤

老年斑中存在大量β 淀粉样蛋白（β-amyloid, Aβ）是老年痴呆症（Alzheimer′s disease, AD）的重要病理特征.大量数据表明，Aβ上具有与过渡态金属离子共价结合的位点，二者能结合成为寡聚复合物. Aβ_1-40Cu（Ⅱ）复合物通过Cu²⁺的还原催化O₂产生H₂O₂但反应机制不清.本文尝试以天然抗氧化剂维生素C（VC）来对抗Aβ_1-40及Aβ_1-40Cu（Ⅱ）复合物产生的H₂O₂对原代培养的神经细胞的毒性.结果表明，VC能够起到显著的保护作用，其有效浓度为1mmol/L.本文用胞外乳酸脱氢酶泄漏量和H₂O₂生成量的数据证实了细胞存活率（MTT实验）的实验结果.这些结果表明，Aβ_1-40Cu（Ⅱ）复合物能够释放更多的H₂O₂，引发细胞膜破裂并最终引起细胞死亡.加入VC后，神经元受到的损伤较轻，提示VC在保护细胞免受氧化损伤方面发挥了重要作用.

Protective Effects of Vitamin C Against Oxidative Stress Induced by Aβ1-40 Cu(Ⅱ) Complexes

An important pathologic hallmark of Alzheimer′s disease (AD) is senile plaque that mainly consists of β-amyloid (Aβ) peptide. Mounting evidence show that Aβ can form oligomeric complexes via binding transitional metal ions, such as Cu(Ⅱ) andFe(Ⅲ). Aβ_1-40Cu(Ⅱ) complexes generate neurotoxic H₂O₂ from O₂ via Cu²⁺ reduction, though the precise reaction mechanism is unclear. In the present study, vitamin C was used to abolish the cytotoxicity that was induced by Aβ_1-40 or the Aβ_1-40Cu（Ⅱ）complexes to cultured primary cortical neurons. The results favor markedly protective effects of vitamin C on injured neurons with the effective concentration being 1 mmol/L. The data derived from lactate dehydrogenase (LDH) released and the production of H₂O₂ were in accordance with the results obtained from the MTT assay, which indicated that binding of copper to Aβ₁-₄₀ increased the production of H₂O₂, leading to a breakdown in the integrity of the plasma membrane and eventually cell death. By contrast, neurons treated with vitamin C exhibited much slighter such damage. These results suggest that vitamin C plays a key role in protecting cells from oxidative damage.