天津医药

天津医药 ›› 2018, Vol. 46 ›› Issue (7): 673-677.doi: 10.11958/20180368

• 细胞与分子生物学 •    下一篇

杜拉鲁肽对阿尔茨海默病样神经退行性变的保护作用

陈沿霖，郭爱，彭鹏，周梅，谷中娅，刘筱晗，张梦喆，邓艳秋△   

  1. 天津医科大学基础医学院生理学与病理生理学系（邮编300070）
  • 收稿日期:2018-03-13 修回日期:2018-05-30 出版日期:2018-07-15 发布日期:2018-07-15
  • 通讯作者: 陈沿霖 E-mail:196179862@qq.com
  • 作者简介:陈沿霖（1990），男，硕士在读，主要从事神经退行性变方面研究
  • 基金资助:
    减弱的胰岛素信号在AD神经退行性变的作用和相关的治疗研究;西格列汀对AD样小鼠学习记忆障碍的保护作用及机制;杜拉鲁肽鼻腔给药对AD样小鼠学习记忆障碍的保护作用及机制

The protective effects of dulaglutide on AD-like neurodegenerative changes

CHEN Yan-lin, GUO Ai, PENG Peng, ZHOU Mei, GU Zhong-ya, LIU Xiao-han, ZHANG Meng-zhe, DENG Yan-qiu△   

  1. Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China △Corresponding Author E-mail: 1766464240@qq.com
  • Received:2018-03-13 Revised:2018-05-30 Published:2018-07-15 Online:2018-07-15
  • Contact: Yan-Lin CHEN E-mail:196179862@qq.com
  • Supported by:
    Impaired insulin signaling in the neurodegeneration of AD and related treatment

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摘要： 目的 研究杜拉鲁肽（dulaglutide）对阿尔茨海默病（AD）样神经退行性变的保护作用及其机制。方法 应 用糖尿病治疗新药杜拉鲁肽观察和探讨其对人神经瘤母细胞SH-SY5Y细胞AD样变的影响及机制。采用MTT方法 检测各药物杜拉鲁肽、PI3K抑制剂渥曼青霉素（wortmannin）、胰高血糖素样肽-1（GLP-1）受体拮抗剂Ex9-39对细胞 活性的影响；采用蛋白免疫印迹方法检测各组细胞tau蛋白和神经丝（neurofilaments，NFs）蛋白以及PI3K/GSK-3β信 号通路中关键酶磷酸化水平。结果 杜拉鲁肽改善wortmannin诱导的细胞活性损伤，减少神经细胞内tau和NFs蛋 白的磷酸化水平，提高p-PI3K（p85）和p-GSK3β（S9）的表达水平。而Ex9-39则拮抗杜拉鲁肽的神经保护作用。结 论 杜拉鲁肽可通过PI3K /GSK-3β胰岛素信号通路来保护SH-SY5Y神经细胞的AD样退行性变。

关键词: 阿尔茨海默病, 胰高血糖素样肽1, 1-磷脂酰肌醇3-激酶, tau蛋白质类, 杜拉鲁肽, 胰岛素信号通路

Abstract: Objective To investigate the protective effects of dulaglutide on Alzheimer’s disease (AD) - like neurodegenerative changes and its mechanism thereof. Methods Dulaglutide，a new drug for diabetes, was applied to observe and explore AD-like neurodegenerative changes induced by PI3K inhibitor wortmannin in SH-SY5Y cells. MTT assay was used to observe the cell vitality induced by dulaglutide, wortmannin and glucagon-like peptide (GLP-1) 1 receptor antagonist ex9-39. Western blot assay was used to detect the levels of phosphorylated Tau, neurofilaments (NFs) and the proteins of PI3K/GSK-3β signaling pathway. Results Dulaglutide improved the impaired vitality, increased the levels of phosphorylated PI3K and GSK-3β and decreased phosphorylation levels of tau and NFs induced by wortmannin in SHSY5Y cells. Ex9-39 antagonized the effects of Dulaglutide. Conclusion Dulaglutide protects SH-SY5Y cells from ADlike neurodegenerative changes through improving PI3K /GSK-3β insulin signaling pathway.

Key words: Alzheimer disease, glucagon-like peptide 1, 1-phosphatidylinositol 3-kinase, tau proteins, dulaglutide, insulin signaling pathway