康小红,王艺明
KANG Xiaohong,WANG Yiming

• 1:贵州医科大学附属医院精神科

摘要(Abstract)：

目的 探讨白藜芦醇（Res）对阿尔茨海默病（AD）小鼠前额叶皮质沉默信息调节因子2相关酶I(SIRT1)、维甲纬酸受体β(RARβ)、含有解整合素和金属蛋白酶结构域的蛋白10(ADAM10)表达及Tau蛋白磷酸化水平的影响。方法 选取6月龄C57BL/6雄性小鼠6只作为空白对照组（BC组，生理盐水灌胃），6月龄APPswePSEN1dE9(APP/PS1)转基因小鼠12只制备AD小鼠模型后均分为AD组（生理盐水灌胃）、AD+Res组（800 mg/kg Res灌胃），采用Morris水迷宫实验（MWM）检测3组小鼠6月龄和9月龄时找到水中平台的时间；9月龄小鼠完成MWM后麻醉处死，取前额叶皮质，采用荧光实时定量聚合酶链式反应（RT-qPCR）技术检测3组小鼠前额叶皮质SIRT1和ADAM10 mRNA表达水平，采用免疫蛋白印迹（Western blot）技术检测3组小鼠前额叶皮质SIRT1、RARβ及ADAM10蛋白表达及Tau蛋白磷酸化位点Ser396位点[p-tau(S396)]磷酸化水平。结果 9月龄AD组和AD+Res组小鼠小鼠较本组6月龄时找到水中平台的时间延长（P<0.01）,9月龄AD组小鼠较同月龄BC组小鼠找到平台的时间延长（P<0.01）;AD组小鼠前额叶皮质SIRT1和ADAM10 mRNA表达水平较BC组小鼠下降（P<0.01）,AD+Res组小鼠前额叶皮质ADAM10 mRNA表达水平较AD组升高（P<0.01）;AD组小鼠前额叶皮质SIRT1、RARβ、ADAM10蛋白表达水平较BC组降低（P<0.01）,AD+Res组小鼠前额叶皮质SIRT1、ADAM10表达水平较AD组升高（P<0.05）;AD组小鼠前额叶皮质p-tau(S396)磷酸化水平较BC组升高（P<0.001）,AD+Res组小鼠前额叶皮质p-tau(S396)磷酸化水平较AD组降低（P<0.01）。结论 Res可改善AD小鼠的认知功能，其机制可能与AD小鼠前额叶SIRT1、RARβ及ADAM10表达上调和Tau蛋白磷酸化水平降低有关。
Objective To investigate the effects of resveratrol on the expression levels of silencing information regulator 2 related enzymeⅠ（SIRT1）, retinoic acid receptor β(RARβ), a disintegrin and metalloproteinase domain-containing protein 10( ADAM10), and Tau protein phosphorylation in the mice prefrontal cortex of Alzheimer's disease.Methods Six-month-old mice including six C57BL/6male mice and twelve APPswePSEN1dE9( APP/PS1) transgenic mice. C57BL/6 male mice were selected as blank control group( BC), APP/PS1 mice were divided into Alezhemer's disease group(AD) and restratrol treatment group( AD + Res) by random number table method. AD + Res mice were gavaged with 800 mg/kg resveratrol at a fixed time every day for 3 months, and the other two groups were gavaged with the same amount of normal saline. The cognitive ability of mice aged 6months and 9 months was measured by Morris water maze(MWM). Real time fluorescent quantitative Polymerase Chain Reaction(RT-qPCR) was used to detect the mRNA expression levels of SIRT1 and ADAM10. Western blot was used to detect the protein expression levels of SIRT1, RARβ and ADAM10, as well as the phosphorylation level of Tau protein at Ser396 [p-tau(S396)].Result The mice in AD group and AD + Res group of 9-month-old to find the water platform was longer than 6-month-old in the same set of group(P< 0. 01), and the AD group to find the platform was longer than that of BC group mice(P< 0. 01). The mRNA expression levels ofSIRT1 andADAM10 in prefrontal cortex in AD group were lower than those in BC group(P< 0. 01), and the mRNA expression levels of ADAM10 in prefrontal cortex of AD + Res group was increased compared with that of AD group(P<0. 01). The expression levels of SIRT1, RARβ, and ADAM10 protein in prefrontal cortex of AD group were lower than those in BC group(P< 0. 01), and the SIRT1 and ADAM10 protein in prefrontal cortex of AD + Res group were higher than those in AD group(P< 0. 05). The phosphorylation level of P-tau(S396) in prefrontal cortex of AD group was higher than that of BC group(P< 0. 001), and the phosphorylation level of p-tau(S396) in prefrontal cortex of AD + Res group was lower than that of AD group(P< 0. 01).Conclusion The expressions of SIRT1, RARβ, and ADAM10 in the prefrontal cortex of AD are decreased, and the phosphorylation level of p-tau(S396) is increased. Resveratrol can improve the cognitive function of AD, increase the expression levels of SIRT1, RARβ, and ADAM10 in the prefrontal cortex of AD, and decrease the phosphorylation level of p-tau(S396).

关键词(KeyWords)： 阿尔茨海默病;Tau蛋白质类;白藜芦醇;水迷宫;沉默信息调节因子2相关酶Ⅰ;维甲纬酸受体β;含有解整合素和金属蛋白酶结构域的蛋白10
Alzheimer 's disease (AD);Tau proteins;resveratrol (Res);mirrors water maze (MWM);silencing information regulator 2 related enzyme Ⅰ （ SIRT1 ）;retinoic acid receptor β (RARβ);a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10)

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金（81960262）

作者(Author): 康小红,王艺明
KANG Xiaohong,WANG Yiming

DOI: 10.19367/j.cnki.2096-8388.2022.06.004

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