中文摘要：

目的探讨褪黑素（Mel）对花萼海绵诱癌素（CA）在成神经瘤细胞诱导的tau蛋白过度磷酸化的影响及其机制。方珐采用鼠野生型成神经瘤细胞（N2awt），给予CA处理，或同时给予50μlmol／LMel处理，用免疫荧光检测tau蛋白磷酸化水平，”P-特异底物标记技术检测GSK-3活性，免疫印迹技术检测P-Ser9-GSK-30和GSK-3β的表达水平，计算P-Ser9-GSK-3β／GSK-38的比率。结果①CA可在N2awt细胞使tau蛋白在Ser396／404位点和Serl98／202位点过度磷酸化，同时伴有GSK-3活性升高和P-Ser9-GSK-3β表达水平降低。②Mel对CA引起的tau蛋白过度磷酸化有保护作用；Mel同时对抗CA诱导的GSK-3活性升高和P-Ser9-GSK-3β表达水平降低。结论Mel可减轻CA引起的tau蛋白过度磷酸化，其机制可能与调节细胞内P-Ser9-GSK-3β的表达水平和改变GSK-3活性有关。

英文摘要：

Objective To investigate the in vivo effect of melatonin （Mel） on calyculin A（CA）-induced tau hyperphosphorylation in neuroblastoma cells （N2awt）. Methods We treated N2awt cells with CA or CA and 50 μmol/L Mel, detected the level of tau phosphorylation with immunofluorescence, and assayed the activities of GSK-3 and the ratio of GSK-3β phosphorylated at Ser9 site to total GSK-3β. Results CA treatment led to tau hyperphosphorylation accompanied with the increased activity of GSK-3 and the decreased ratio of GSK-3β phosphorylated at Ser9 site to total GSK-3β. When the cells were incubated simultaneously with CA and 50 μmol/L Mel, the CA-induced tau hyperphosphorylation, GSK-3 activation and the ratio of GSK-3β phosphorylated at Ser9 site to total GSK-3β decrease were attenuated. Conclusion Melatonin protects neuroblastoma cells from CA-induced tau hyperphosphorylation. Its protection may be related to the regulation of GSK-3 activity and the ratio of GSK-3β phosphorylated at Ser9 site to total GSK-3β increase.