【摘要】 目的　用脑片研究花萼海绵诱癌素 (CA)诱导骨架蛋白tau过度磷酸化 ,以及褪黑素 (MT)的保护作用及可能机制。方法　培养大鼠前脑脑片 ,分为 5组 :A组 :正常对照组 ,B组 :0 1μmol/LCA组 ,C组 :10 μmol/LMT +0 1μmol/LCA组 ,D组 :4 0 μmol/LMT +0 1μmol/LCA组 ,E组 :80 μmol/LMT +0 1μmol/LCA组。用免疫印迹法检测tau的磷酸化程度 ,同时检测脑片组织丙二醛 (MDA)含量及超氧化物歧化酶 (SOD)活性。结果0 1μmol/LCA使tau蛋白在Ser396 / 4 0 4、Ser198/ 199/ 2 0 2位点的磷酸化程度显著升高 ,脑片的MDA含量及SOD活性显著升高 ;MT能使tau蛋白在Ser396 / 4 0 4、Ser198/ 199/ 2 0 2位点的磷酸化水平显著降低 ;显著降低CA处理增高的脑片MDA水平 ,提高SOD活性。结论　CA能够诱导前脑脑片tau蛋白发生过度磷酸化 ;MT对CA诱导的tau蛋白过度磷酸化具有保护作用。为深入探讨阿尔茨海默病发病机制和防治方法提供了实验依据。更多还原

【Abstract】 Objective To investigate hyperphosphorylation of tau induced by calyculin A (CA), the protective effect of melatonin (MT) and the mechanism. Methods The forebrain slices were cultured and divided into 5 groups: group A (control group), group B (0.1 μmol/L CA), group C (10 μmol/L MT+0.1 μmol/L CA), group D (40 μmol/L MT+0.1 μmol/L CA), group E (80 μmol/L MT+0.1 μmol/L CA). The level of phosphoprotein of tau, the content of maleic dialdehyde (MDA) and the activities of superoxide dismutase (SOD) were detected. Results The treatment of forebrain slices with 0.1 μmol/L CA resulted in hyperphosphorylation of tau at Ser396/404, Ser198/199/202. It also elevated the level of MDA with a concurrent activation of SOD. MT significantly reduced phosphorylation level of tau at Ser396/404, Ser198/199/202. Additionally, MT significantly reduced MDA level that had been increased by CA and increased the activities of SOD. Conclusion CA can induce hyperphosphorylation of tau in cultured forebrain slices; MT has a protective effect on hyperphosphorylation of tau induced by CA. The experimental results provide the experimental evidence for further studying the pathogenesis and prevention and treatment of Alzheimer disease.更多还原