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山东大学学报(医学版) ›› 2010, Vol. 48 ›› Issue (7): 33-36.

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JAK/STAT途径介导Aβ寡聚体诱导小胶质细胞TNF-α的释放

杨丽玲,王璐,任晓燕,韩晓娟,杜怡峰   

  1. 山东大学附属省立医院神经内科,济南 250021
  • 收稿日期:2009-12-15 出版日期:2010-07-16 发布日期:2010-07-16
  • 通讯作者: 杜怡峰(1962- ),男,教授,博士生导师,主要从事老年性痴呆、神经变性病以及脑血管病发病机制及防治的研究。Email:duyifengpmd2000@yahoo.com.cn
  • 作者简介:杨丽玲(1982- ),女,硕士研究生,主要从事老年性痴呆发病机制的研究。 Email:yangliling.123@163.com
  • 基金资助:

    国家自然科学基金资助项目(30973816)

JAK/STAT signaling pathway mediates β-amyloid protein-induced TNF-α action of microglia in vitro

YANG Li-ling, WANG Lu, REN Xiao-yan, HAN Xiao-juan, DU Yi-feng   

  1. Department of Neurology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, China
  • Received:2009-12-15 Online:2010-07-16 Published:2010-07-16

摘要:

目的 研究β淀粉样蛋白(Aβ)寡聚体对晚期糖基化蛋白相关受体(RAGE)介导小胶质细胞产生炎症反应的影响,分析Janus 激酶/ 信号转导和转录激活子(JAK/STAT)途径与Aβ寡聚体诱导肿瘤坏死因子α(TNF-α)释放的关系。方法  取经过刺激及阻断处理原代培养的小胶质细胞,经酶联免疫吸附法(ELISA)检测细胞上清液TNF-α的水平。结果   经Aβ寡聚体处理24h后TNF-α表达增加,分别经抗RAGE IgG和AG490预处理后再经Aβ寡聚体处理小胶质细胞,TNF-α释放明显被抑制。 结论   RAGE是Aβ寡聚体诱导小胶质细胞炎症反应的受体,JAK/STAT途径可能参与Aβ寡聚体诱导小胶质细胞TNF-α的释放。

关键词: 淀粉样β蛋白;小神经胶质细胞;糖基化终产物,高级;信号传导;肿瘤坏死因子

Abstract:

Objective  To explore the inflammatory response of microglia induced by β-amyloid (Aβ) oligomers through the receptor for advanced glycation end product (RAGE) ,and to further analyze the relationship between Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway and tumor necrosis factor-α (TNF-α) of microglia induced by Aβoligomers. Methods   After the primary rat microglial cells were stimulated and obstructed, the level of TNF-α extracted from supernatant liquid of microglia was measured by enzyme-linked immunosorbent assay (ELISA). Results   TNF-αwas increased after primary rat microglia cells  were treated by Aβoligomers for 24h. However, anti-RAGE IgG and AG490 reduced the activation of microglia cells and obviously inhibited Aβ oligomer-induced release of TNF-α. Conclusions    RAGE is the receptor of microglia in inflammatory response induced by Aβ oligomer. JAK/STAT pathway may participate in the release of TNF-α induced by Aβ oligomer.

Key words: Amyloid beta-protein; Microglia; Glycosylation end products, advanced; Signal transduction; Tumor necrosis factor

中图分类号: 

  • R741.04
[1] 闫鹏 王蓉 杜怡峰 沈伦乾. 老年性痴呆患者尿中AD7c-NTP含量的研究[J]. 山东大学学报(医学版), 2209, 47(6): 106-.
[2] 闫鹏 王蓉 杜怡峰 沈伦乾. 老年性痴呆患者尿中AD7c-NTP含量的研究[J]. 山东大学学报(医学版), 2009, 47(6): 106-.
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