[1]缪茂军 陈小武 曹学兵等. mTOR信号通路在左旋多巴诱发异动症中的作用及机制研究[J].卒中与神经疾病杂志,2016,23(03):182-189.[doi:10.3969/j.issn.1007-0478.2016.03.011]
 [J].Stroke and Nervous Diseases,2016,23(03):182-189.[doi:10.3969/j.issn.1007-0478.2016.03.011]
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 mTOR信号通路在左旋多巴诱发异动症中的作用及机制研究(/HTML)
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第23卷
期数:
2016年03期
页码:
182-189
栏目:
论 著
出版日期:
2016-06-24

文章信息/Info

作者:
 缪茂军 陈小武 曹学兵等
 570102 海口,海南医学院附属医院神经内科[缪茂军 陈志斌(通信作者)陈小武]; 华中科技大学同济医学院附属协和医院神经内科(曹学兵)
关键词:
 异动症 帕金森病 mTOR 雷帕霉素 纹状体 突触可塑性
分类号:
R
DOI:
10.3969/j.issn.1007-0478.2016.03.011
文献标志码:
A
摘要:
 目的 探讨mTOR(Mammalian target of rapamycin,哺乳动物雷帕霉素靶蛋白)信号通路的激活在左旋多巴诱发异动症(L-Dopa Induced Dyskinesia,LID)大鼠纹状体中的作用及机制。方法 普通级SD雄性大鼠共54只,随机分为5组,8只正常组(N组),剩下8只帕金森病(Parkinson’s disease)模型; 异动症组10只、余均分为雷帕霉素(Rapamycin)作为药物治疗组即干预组和Rapamycin溶剂的对照组(C组)各14只; 记录下对照组与干预组的行为学并进行异动症AIM评分,每周至少两次; 用western blot技术测定N组、PD组、LID、C组以及R组纹状体组织的免疫印迹,验证所用NMDA受体亚基NR1(Ser896)、NR2A(Y1325)、NR2B(Y1472)位点磷酸化及PSD-95、p-PSD95(S295)磷酸化位点的抗体特异性的变化。结果(1)对照组第1,3,5天时间点行为学AIM评分与干预组无差异(P>0.05),第8天时间点行为学AIM评分与对照组比较,干预组AIM评分有下降(P<0.01),之后第9、10、13、16、18、21天2组仍然有明显差异,干预组AIM评分无反弹上升现象。(2)LID组大鼠纹状体PSD-95及p-PSD95(s295)表达水平较其他组高; 干预后两者的表达水平明显下降(P<0.05)。PSD-95及p-PSD95(S295)在正常组表达水平最低,在异动症组和对照组最高,无差异(P>0.05); 与正常组外其他组对比,干预组两者的表达水平明显下降(P<0.05); 干预组与正常组的表达水平无明显差异(P>0.05)。(3)LID组、对照组NMDA受体亚基NR1(Ser896)、NR2A(Y1325)、NR2B(Y1472)位点磷酸化的表达水平较干预组有所增高(P均<0.05)。结论(1)mTOR参与了LID的发病,应用mTOR特异性抑制剂雷帕霉素对LID的治疗有效。(2)大鼠纹状体区的mTOR信号调理与LID的发生密切相关,mTOR激活对纹状体突触水平具有调节作用,可能通过依赖突触分子PSD-95以及NMDAR各亚型的磷酸化水平导致突触可塑性发生适应改变,最终产生和维持皮质纹状体突触“病理性LTP”,从而介导了LID发生。

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备注/Memo

备注/Memo:
 (2015-11-12收稿 2016-04-12修回)
基金项目:国家自然科学基金资助项目(项目编号为31260241)
更新日期/Last Update: 2016-06-24