洛伐他汀减轻冈田酸诱导的大鼠皮质神经元Tau蛋白过度磷酸化  

Lovastatin Attenuates Okadaic acid-induced Tau Protein Superphosphorylation in Rat Cortical Neurons

作　　者：马涛[1] 陈耀民[1] 赵永波[1] 

机构地区：[1]上海交通大学附属第一人民医院神经科,上海200080

出　　处：《实用临床医药杂志》2008年第3期34-37,48,共5页Journal of Clinical Medicine in Practice

基　　金：美国阿尔茨海默氏症协会基金资助项目(IIRG-06-26070)

摘　　要：目的探讨洛汀(LOV)对冈田酸(OA)诱导的大鼠皮质神经元Tau蛋白过度磷酸化的影响。方法选用孕期17d的SD大鼠,取皮质神经元接种培养。待优化OA处理时间和剂量等条件后,实验分为阴性对照组、OA组、LOV组、LOV预处理+OA组。通过免疫印迹法检测皮层神经元Tau蛋白磷酸化水平、总Tau蛋白水平。结果应用OA 30 nmmol/L处理大鼠皮质神经元1 h,成功诱导Tau蛋白过度磷酸化,而不明显影响细胞活力。LOV 500 nM预处理4 d能在Thr181(AT270),Thr231(AT180),Ser202/Thr205(AT8)和Ser396等磷酸化位点显著减轻冈田酸诱导的大鼠皮质神经元Tau蛋白过度磷酸化,而不影响总Tau蛋白水平。结论洛伐他汀减轻冈田酸诱导的大鼠皮质神经元Tau蛋白过度磷酸化,提示洛伐他汀对Tau相关神经病理有潜在的神经保护作用。Abnormal phosphorylation of microtubule-associated protein tau plays a critical roie in Alzheimer＇s disease （AD）. Okadaic acid （OA）, a specific inhibitor of protein phosphatase-2A （PP-2A） and PP-1, is used as a research model of AD to increase the tau phosphorylation. To search for the means to arrest Alzheimer-like damages, in this study we treated rat cortical neurons with okadaic acid to mimic an Alzheimer-like phosphatase-deficient system and induced the tau hyperphosphorylation, then observed the effect of lovastatin on tau hyperphosphorylation induced by OA. The levels of total and phosphorylated tau were measured. It was found that lovastatin attenuated OA-induced hyperphosphorylation of tau at Thrl81 （AT270）, Thr231 （AT180）, Ser202/ Thr205 （AT8） and Ser396. These results indicate that lovastatin has potential neuroprotective effects on Tau-related neuropathology.

关 键 词：洛伐他汀 阿尔茨海默病 冈田酸 TAU蛋白 磷酸化 

分 类 号：R741.02[医药卫生—神经病学与精神病学]