中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (29): 2744-2753.doi: 10.3969/j.issn.1673-5374.2013.29.006

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

Toll样受体4介导的信号通路参与海马神经元凋亡

  

  • 收稿日期:2013-06-08 修回日期:2013-07-22 出版日期:2013-10-15 发布日期:2013-10-15

Toll-like receptor 4-mediated signaling participates in apoptosis of hippocampal neurons

Yue He1, 2, Ailing Zhou1, Wei Jiang3   

  1. 1 Department of Pathophysiology, Medical College, Nantong University, Nantong 226001, Jiangsu Province, China
    2 Department of Neurology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
    3 Department of Scientific Technology and Property, Nantong University, Nantong 226019, Jiangsu Province, China
  • Received:2013-06-08 Revised:2013-07-22 Online:2013-10-15 Published:2013-10-15
  • Contact: Ailing Zhou, Master, Professor, Department of Pathophysiology, Medical College, Nantong University, Nantong 226001, Jiangsu Province, China, ALZ@ntu.edu.cn.
  • About author:Yue He, Master.

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摘要：

磷脂酰肌醇-3激酶/蛋白激酶B信号转导通路被视为是参与细胞存活的最重要的信号通路之一，能够介导多种抗凋亡效应。实验利用此种信号通路之一相关的特异性抑制剂及Toll样受体抗体影响培养的海马神经元中Toll样受体4-磷脂酰肌醇3激酶/蛋白激酶B-糖原合酶激酶3β信号转导通路的作用。结果发现与正常培养的海马神经元相比，脂多糖刺激后海马神经元凋亡率增加，细胞中磷酸化蛋白激酶B Ser473和磷酸化糖原合酶激酶βSer9表达均明显下降，但Caspase-3表达和Bax/Bcl-2比值增加；而在脂多糖干预前加入Toll样受体4抗体或糖原合酶激酶3β抑制剂氯化锂（LiCl），均能拮抗上述现象；但加入蛋白激酶B-抑制剂LY294002则加剧上述现象。结果证实Toll样受体4-磷脂酰肌醇3激酶/蛋白激酶B-糖原合酶激酶3β信号通路可能参与了脂多糖诱导的海马神经元的凋亡。

关键词: 神经再生, 脑损伤, 海马, 神经元, Toll样受体4, 磷脂酰肌醇3激酶/蛋白激酶B-糖原合酶激酶3β信号通路, 细胞凋亡, 基金资助文章

Abstract:

The phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling pathway is considered important for cell survival and has been shown to mediate various anti-apoptotic biological effects. This study explored the role of the Toll-like receptor 4 (TLR4)-mediated PI3K/AKT-glycogen syn-thase kinase 3β (GSK-3β) signaling pathways in lipopolysaccharide-induced apoptosis in a primary culture of hippocampal neurons. Results demonstrated that the apoptotic ratio of hippocampal neurons stimulated by lipopolysaccharide was significantly higher compared with the control group. Both the expression of P-AKTSer473 and P-GSK-3βSer9 in hippocampal neurons stimulated by lipo-polysaccharide decreased compared with the control, while the level of active Caspase-3 and the ratio of Bax/Bcl-2 were significantly increased. The level of active Caspase-3 and the ratio of Bax/Bcl-2 in hippocampal neurons treated with TLR4 antibody or the GSK-3β inhibitor, LiCl, de-creased before intervention with lipopolysaccharide, but increased after treatment with the AKT in-hibitor, LY294002. These findings suggest that the TLR4-PI3K/AKT-GSK3β signaling pathway may be involved in lipopolysaccharide-induced apoptosis of hippocampal neurons.