中文摘要：

阿尔茨海默症（Alzheimer’s disease，AO）是老年人群中最常见的认知障碍疾病之一。阿尔茨海默症与糖尿病（diabetes mellitus，DM）拥有某些相似的病理机制，因此我们推测抗糖尿病钒化合物可能具有抗AD活性。本文研究了双乙酰丙酮氧钒（vanadyl acetylacetonate，VO（acac）2）和肉桂醛（cinnamaldehyde，CA）对SH—SY5Y神经细胞及AD模型的作用。结果显示，VO（acac）2在微摩尔浓度水平可以提高SH．SY5Y神经细胞及过表达p淀粉样蛋白（A13）细胞的活力；VO（acac）2与CA的联合使用对正常和负载A13的神经细胞都具有加和的保护作用。更进一步实验发现，VO（acac）2可以激活神经细胞中PPAR7-AMPK的信号转导通路，抑制导致Tau蛋白的过度磷酸化的重要酶—GsK3p的活化；而CA可以恢复A13诱导的线粒体分裂，从而增强线粒体功能。此外，VO（acac）：与CA都能降低细胞内活性氧水平并抑制毒性的低分子量A13寡聚体形成。综上所述，VO（acac）：能与CA协同作用，改善B淀粉样蛋白导致的神经细胞损伤。本工作为钒金属药物的应用提示了新的发展方向。

英文摘要：

The Alzheimer＇s disease （AD） is one of the common cognitive disorders in the elderly. AD shares some similar pathological characters with diabetes mellitus （DM）, suggesting potential application of anti-diabetic agents, such as vanadyl complexes, in therapeutic treatment of AD. In the present work, we studied the effects of vanadyl acetylacetonate （VO（acac）2） and cinnamaldehyde （CA） on an AD model based on SH-SY5Y neural cells. The experimental results showed that VO（acac）2 at sub-micromolar concentrations could improve the viability of neural cells with or without increased β-amyloid （Aβ） burden; and the combination of VO（acac）2 and CA showed an additive cell protection effects. Further investigation revealed that for SH-SY5Y neural cells, VO（acac）2 could activate PPART-AMPK signal transduction and inhibit GSK 3β, one of the major kinases for Tau hyperphosphorylation. Meanwhile, CA could correct the abnormal mitochondrial morphology due to Aβ-induced excessive mitochondrial fission, thus restoring/enhancing the mitochondrial function. In addition, both VO（acac）2 and CA decreased intracellular reactive oxygen species （ROS） level and inhibited formation of toxic Aβ oligomers. Overall, VO（acac）2 might work with CA in improving the neural cell viability under the Aβ burden, suggesting application of vanadium metallodrugs in AD treatment.