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当代阿耳茨海默病研究

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

姜黄素通过CaMKKβ依赖性激活AMP激活蛋白激酶信号通路,诱导小胶质细胞转化为M2表型,从而预防神经炎症

卷 17, 期 8, 2020

页: [735 - 752] 页: 18

弟呕挨: 10.2174/1567205017666201111120919

价格: $65

摘要

背景:神经炎症在各种神经退行性疾病的病理生理过程中起着重要作用。众所周知,姜黄素在多种神经炎症模型中具有明显的抗炎作用。然而,它对小胶质细胞极化调制的影响在很大程度上是未知的。 目的:本研究旨在探讨姜黄素是否通过激活AMPK (AMP-activated protein kinase, AMPK)信号通路改变小胶质细胞为抗炎M2表型。 方法:采用LPS处理建立BV2细胞和原代小胶质细胞神经炎症模型。在脑外侧间隔复合体区注射脂多糖(LPS)建立神经炎症小鼠模型。ELISA法测定TNF-α,细胞计数试剂盒-8 (CCK-8)法测定细胞活力。Q-PCR和Western blot检测促炎细胞因子和抗炎细胞因子的表达。免疫荧光法检测BV2小胶质细胞表型极化。 结果:姜黄素在LPS存在或不存在的情况下增强了BV2小胶质细胞中AMPK的激活。在LPS刺激下,姜黄素的加入促进了BV2细胞的M2极化,表现为抑制M1,提高M2信号蛋白和基因表达。姜黄素的作用受到AMPK抑制剂或AMPK基因敲低的抑制。钙调蛋白依赖性蛋白激酶激酶β(CaMKKβ)和肝激酶B1 (LKB1)是激活AMPK的上游激酶。姜黄素可以激活不表达LKB1的Hela细胞中的AMPK。然而,CaMKKβ抑制剂和siRNA都阻断了lps刺激的BV2细胞中AMPK的姜黄素激活。此外,CaMKKβ抑制剂和siRNA削弱了姜黄素抑制对lps刺激BV2细胞M1和M2蛋白及基因表达的影响。最后,在体内神经炎症模型中,姜黄素增强了LPS刺激下小胶质细胞过度激活的脑区AMPK激活。姜黄素在该体内模型中还抑制M1,促进M2信号蛋白和基因表达。 结论:姜黄素通过CaMKKβ依赖性AMPK信号通路增强小胶质细胞M2极化。此外,研究发现姜黄素具有神经保护作用,可作为治疗阿尔茨海默病、帕金森病等神经退行性疾病的新药物。

关键词: 姜黄素,小胶质细胞,AMPK,神经炎症,细胞因子,帕金森病。

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