远志皂苷减轻Aβ_(1-40)诱导的AD大鼠脑神经元tau蛋白Ser^(396)位点的过度磷酸化  

Effect of tenuigenin on tau protein phosphorylation at Ser^(396) site in neurons of AD rats induced by Aβ_(1-40)

作　　者：徐柯乐[1] 陈勤[1] 刘伟[1] 姚媛媛[1] 夏醒醒[1] 张蓓蕾[1] 李燕斐[1] 

机构地区：[1]安徽大学生命科学学院安徽省中药研究与开发重点实验室,安徽合肥230039

出　　处：《中国病理生理杂志》2012年第9期1605-1609,共5页Chinese Journal of Pathophysiology

基　　金：安徽省教育厅自然科学研究项目(No.KJ2009A116;No.KJ2011068);安徽省教育厅省级<细胞生物学>精品课程项目(No.2009024);教育部大学生创新性实验项目(No.2041044)

摘　　要：目的:探讨远志皂苷对β-淀粉样肽1-40(Aβ1-40)诱导的阿尔茨海默病(AD)大鼠脑神经元tau蛋白过度磷酸化的影响。方法:大鼠右侧海马CA1区注射Aβ1-40建立AD模型,并用远志皂苷(18.5 mg/kg、37.0mg/kg和74.0 mg/kg)对大鼠进行灌胃治疗;免疫组织化学染色法观察大脑神经元中总tau蛋白、p-tau(Ser396)、蛋白激酶A(PKA)和蛋白磷酸酶2A(PP2A)蛋白的表达;蛋白免疫印迹技术检测大脑神经元中总tau蛋白含量、tau蛋白Ser396位点磷酸化以及PKA、PP2A蛋白的表达水平。结果:与对照组相比,Aβ1-40组大脑神经元中总tau蛋白含量、tau蛋白Ser396位点磷酸化水平和PKA蛋白的表达水平显著升高,而PP2A蛋白的表达水平明显降低。与Aβ1-40组相比,远志皂苷各治疗组大鼠大脑神经元中总tau蛋白含量、tau蛋白Ser396位点磷酸化水平和PKA蛋白表达水平下降明显,而PP2A蛋白表达水平显著升高。结论:远志皂苷可能是通过下调PKA蛋白表达量,上调PP2A蛋白表达量,减轻AD大鼠脑神经元中tau蛋白Ser396位点的过度磷酸化,使神经细胞免遭Aβ1-40的毒害。AIM ： To investigate the effect of tenuigenin （TEN） on hyperphosphorylation of tau protein in neu- rons of amyloid β - peptide1 -4o （ Aβ1-40 ） - induced Alzheimer disease （AD） rats. METHODS： Aβ1-40 was injected into hippocampus CA1 region of the rats to establish AD model. TEN at different doses （ 18.5 mg/kg, 37.0 mg/kg and 74.0 mg/kg） was intragastrically administered. The protein expression of protein kinase A （ PKA）, protein phosphatase 2A （PP2A）, total tan and p -tau （Ser^396） in the neurons was observed by the method of immunohistochemistry. The protein content of total tau and p - tau （ Ser^396 ）, and the expression level of PKA and PP - 2A were detected by Western blotting analysis. RESULTS： In Aβ1-40 group, the level of total tau, the phosphorylation of tau protein and the expression of PKA were significantly increased compared with those in Sham operation group. Meanwhile, the expression of PP2A in Aβ1-40 group was lower than that in sham operation group. In TEN treatment group, the level of total tan, the phosphorylation of tan protein and the expression of PKA were markedly decreased, and the expression of PP2A was increased as compared with Aβ1-40 group. CONCLUSION： TEN may protect the neurons from the toxic effect of Aβ1-40 and reduce the hyper- phosphorylation of tan （ Ser^396 ） in the neurons of AD rats by activating the expression of PP2A and inhibiting the expression of PKA.

关 键 词：远志皂苷 Β-淀粉样肽 阿尔茨海默病 大鼠 TAU蛋白 磷酸化 

分 类 号：R966[医药卫生—药理学]