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二苯乙烯苷对 AD 模型小鼠 Tau 蛋白 Thr205 和 Ser404 位点磷酸

        化的影响          Δ


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        吴文雪 ,苏彦兆 ,刘超宇 ,蒙婉莹 ,李振中 ,黄 健 ,朱晓莹 ,廖艳花 ,黄忠仕 (1.右江民族医学院基础医
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        学院,广西 百色 533000;2.广西中医药大学药学院,南宁 530200;3.右江民族医学院药学院,广西 百色
        533000;4.右江民族医学院临床医学院,广西 百色 533000)
        中图分类号 R285.5         文献标志码 A           文章编号 1001-0408(2020)23-2847-06
        DOI  10.6039/j.issn.1001-0408.2020.23.06
        摘   要  目的:研究二苯乙烯苷(TSG)对阿尔茨海默病(AD)模型小鼠 Tau 蛋白 Thr205、Ser404 位点磷酸化的影响,探索 TSG 抗
        AD 的可能机制。方法:将 APP/PS1/Tau 三转基因痴呆(3×Tg-AD)小鼠随机分成模型组、阳性对照组(石杉碱甲,0.15 mg/kg)和
        TSG 低、中、高剂量组(0.033、0.1、0.3 g/kg),每组6只;另取6只C57BL/6J小鼠作为正常对照组。各给药组小鼠灌胃相应药物,模
        型组和正常对照组小鼠灌胃等体积生理盐水,每天给药1次,连续给药60 d。末次给药结束后,采用免疫荧光染色法检测各组小
        鼠脑组织中Tau蛋白和磷酸化Tau蛋白(Thr205、Ser404位点)的分布和表达;采用Western blotting法检测各组小鼠脑组织中磷酸
        化 Tau 蛋白(Thr205、Ser404 位点)的表达水平。结果:与正常对照组比较,模型组小鼠脑组织中 Tau 蛋白和磷酸化 Tau 蛋白
       (Thr205、Ser404位点)表达增多、容易聚集成团、分布更为广泛,相对表达量均显著升高(P<0.01),且Western blotting结果显示磷
        酸化Tau蛋白(Thr205、Ser404位点)的表达水平显著升高(P<0.01);与模型组比较,阳性对照组和TSG各剂量给药组小鼠脑组织
        中Tau蛋白和磷酸化Tau蛋白(Thr205、Ser404位点)表达和聚集减少、分布范围变窄,相对表达量均显著降低(P<0.01),且West-
        ern blotting结果显示磷酸化Tau蛋白(Thr205、Ser404位点)的表达水平也显著降低(P<0.01);与阳性对照组比较,TSG各剂量给
        药组小鼠脑组织中Tau蛋白和磷酸化Tau蛋白(Thr205、Ser404位点)的分布情况差别不大,相对表达量差异均无统计学意义(P>
        0.05),但Western blotting结果显示TSG中、高剂量组小鼠脑组织中磷酸化Tau蛋白(Thr205位点)的表达水平和TSG各剂量组小
        鼠脑组织中磷酸化Tau蛋白(Ser404位点)的表达水平均显著降低(P<0.05或P<0.01)。结论:TSG可能通过下调脑组织中磷酸
        化Tau蛋白(Thr205、Ser404位点)的表达,从而发挥其对AD模型小鼠的抗痴呆作用。
        关键词 阿尔茨海默病;二苯乙烯苷;3×Tg-AD小鼠;Tau蛋白;磷酸化;Thr205位点;Ser404位点
        Effects of Stilbene Glycoside on the Phosphorylation of Thr205 and Ser404 Sites of Tau Protein in AD
        Model Mice
        WU Wenxue ,SU Yanzhao ,LIU Chaoyu ,MENG Wanying ,LI Zhenzhong ,Huang Jian ,ZHU Xiaoying ,LIAO
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        Yanhua ,HUANG Zhongshi(1. College of Basic Medicine,Youjiang Medical University for Nationalities,
        Guangxi Baise 533000,China;2. College of Pharmacy,Guangxi University of TCM,Nanning 530200,China;
        3. College of Pharmacy,Youjiang Medical University for Nationalities, Guangxi Baise 533000, China;
        4. College of Clinical Medicine,Youjiang Medical University for Nationalities,Guangxi Baise 533000,China)
        ABSTRACT   OBJECTIVE:To study the effects of stilbene glycosidec(TSG)on phosphorylation of Thr205,Ser404 sites of Tau
        protein in Aizheimer’s disease(AD)model mice,and to investigate the potential anti-AD mechanism of TSG. METHODS:APP/
        PS1/Tau three transgenes (3 × Tg-AD) mice were randomly divided into model group,positive control group(huperzine,0.15
        mg/kg),TSG low-dose,medium-dose and high-dose groups(0.033,0.1,0.3 g/kg),with 6 mice in each group. In addition,6
        C57BL/6J mice were chosen as normal control group. Administration groups were given relevant medicine intragastrically. Model
        group and normal control group were given equal volume of normal saline intragastrically,once a day,for consecutive 60 days.
        After last medication,immunofluorescence staining was used to detect Tau protein and phosphorylated Tau protein (Thr205,
        Ser404 sites) distribution and expression in brain tissue of mice in each group. Western blotting assay was used to detect
                                                           phosphorylated Tau protein(Thr205,Ser404 sites)expression
           Δ 基金项目:国家自然科学基金资助项目(No.81860709);广西自
                                                           level in brain tissue of mice in each group. RESULTS:
        然科学基金资助项目(No.2018GXNSFAA294153);广西研究生教育
                                                           Compared with normal control group,the expression of Tau
        创新计划项目(No.YCSW2020231)
                                                           protein,phosphorylated Tau protein(Thr205,Ser404 sites)in
           *硕士研究生。研究方向:抗老年痴呆药物研发。E-mail:
        729011126@qq.com                                   the brain tissue of mice were increased in model group,which
           # 通信作者:教授,硕士生导师,博士。研究方向:抗老年痴呆药                  were easy to aggregate and distributed more widely; their
        物研发。电话:0776-2848023。E-mail:hzs1004@163.com         relative expression were increased significantly (P<0.01).


        中国药房    2020年第31卷第23期                                             China Pharmacy 2020 Vol. 31 No. 23  ·2847 ·
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