山茱萸环烯醚萜苷对蛋白磷酸酶抑制剂冈田酸拟阿尔采末病细胞模型的作用  

Effects of cornus officinals iridoid glycoside on cellular model of alzheimer disease induced by protein phosphatase inhibitor okadaic acid

作　　者：褚燕琦[1] 李玮[2] 张兰[1] 王文[1] 艾厚喜[1] 李林[1] 

机构地区：[1]首都医科大学宣武医院药物研究室.教育部神经变性病学重点实验室,北京100053 [2]河南省人民医院神经内科,河南郑州450000

出　　处：《中国药理学通报》2006年第8期960-963,共4页Chinese Pharmacological Bulletin

基　　金：北京市自然科学基金资助项目(No7032013;7050001);北京市科技计划资助项目(NoD0204003000031);北京市科委科技新星计划资助项目(NoH020821390190)

摘　　要：目的探讨中药山茱萸环烯醚萜苷(COIG)对蛋白磷酸酶2A和1(PP2A和PP1)抑制剂冈田酸(okadaicacid,OA)拟阿尔采末病细胞模型tau蛋白过度磷酸化水平和细胞微管的影响。方法COIG与人神经母细胞瘤细胞系SKNSH细胞预孵育24h,再用OA10nmol·L-1与SKNSH细胞共孵育6h,在显微镜下观测细胞形态变化,用Westernblot方法观察磷酸化和非磷酸化tau蛋白表达,用间接免疫荧光法观察神经细胞微管的变化。结果正常SKNSH细胞铺展良好,OA模型组细胞变圆,突起断裂;OA模型组tau蛋白ser199/202和ser404位点磷酸化水平较正常对照组明显增高,非磷酸化水平下降;OA模型组细胞微管平均面积较正常对照组明显减少。COIG(100和200mg·L-1)给药组细胞形态基本恢复正常,tau蛋白ser199/202和ser404位点磷酸化水平较OA模型组明显下降、非磷酸化水平升高,细胞微管平均面积比模型组明显增大。结论山茱萸环烯醚萜苷能够抑制神经细胞tau蛋白过度磷酸化,保护细胞微管结构,因此可能具有治疗AD的应用前景。Aim To investigate effects of Comus Officinals iridoid glycoside （COIG）on hyperphosphorylation of tau protein and microtubule in cellular model of Alzheimer disease （AD） induced by the protein phosphatase inhibitor okadaic acid （OA）. Methods The human neuroblastoma cell line SK-N-SH ceils were cultured with COIG for 24 h, and then incubated with OA at 10 nmol· L^-1 for 6 h. The morphological changes of ceils were observed under microscope. Western blotting was used to determine phosphorylated and nonphosphorylated tau protein expression levels, and indirect immunofluorescence was used to observe the tubule changes of nerve ceils. Results The normal SK-N-SH ceils spread well, but the cell bodies of OA-treated group became round and the processes were broken. At ser-199/202 site and ser404 site, the phosphorylation of tau protein in OA-treated ceils was significantly in-creased compared with the normal group, and the nonphosphorylation of tau protein was obviously decreased. The area of microtubules in OA-treated group was smaller than that of normal control group. Preincubation of COIG （ 100 and 200 mg · L^-1 ） with SK-N-SH ceils prevented above changes induced by OA, including that the cell morphology maintained normal in COIG groups, phosphorylation level was significantly decreased and non-phosphorylation level was increased at ser-199/202 site and ser-404 site of tau protein, and the area of microtubules was obviously enlarged. Conelusiort COIG can inhibit the hyperphosphorylation of tau protein in nerve ceils and protect the structure of microtubules, thus may have potential to treat Alzheimer disease. ：

关 键 词：山茱萸 环烯醚萜苷 冈田酸 TAU蛋白 微管 阿尔采末病 

分 类 号：R282.71[医药卫生—中药学] R322.81[医药卫生—中医学]