南方医科大学学报 ›› 2013, Vol. 33 ›› Issue (08): 1132-.

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β淀粉样蛋白通过升高ROS水平上调晚期糖基化终末产物受体的表达

孔卫娜,张佳,高维娟,刘清涛,周利明,柴锡庆   

  • 出版日期:2013-08-20 发布日期:2013-08-20

β-amyloid protein up-regulates the expression of the receptor for advanced glycation end products by increasing ROS production

  • Online:2013-08-20 Published:2013-08-20

摘要: 目的探讨β淀粉样蛋白(Aβ)调控海马晚期糖基化终产物受体(RAGE)表达及其机制。方法通过脑立体定向仪及微量注
射器于大鼠海马内注射Aβ1~40,注射3周后,利用Western blot检测海马组织RAGE、还原型烟酰胺腺嘌呤二核苷酸(NADPH)氧
化酶(gp9lphox及p47phox亚基)、核因子-κb(NF-κB)、NF-κB抑制蛋白(IκB)的表达变化,利用流式细胞仪检测大鼠海马组织活性氧
(ROS)的变化。结果海马注射Aβ1~40 3周后,海马组织的RAGE的表达显著升高(P<0.01),同时检测到注射Aβ1~40引起海马组织
内ROS水平明显增高(P<0.01),gp9lphox、p47phox的表达及p47phox的磷酸化水平均显著升高(P<0.01),IκBα的表达显著降低(P<
0.01),IκBα的磷酸化水平显著增加(P<0.01),NF-κB的表达及NF-κB的磷酸化水平均显著升高(P<0.01)。结论Aβ可引起海马
组织RAGE的表达升高,NADPH氧化酶/ROS/NF-κB信号通路可能在Aβ诱导海马神经元RAGE的表达过程中发挥重要作用。

Abstract: Objective To investigate the mechanism of β-amyloid protein (Aβ) in regulating the expression of the receptor for
advanced glycation end products (RAGE). Methods Aβ1-40 was injected into the bilateral hippocampus of rats, and 3 weeks
later, the levels of reactive oxygen species (ROS) production were detected by flow cytometry. The expressions of RAGE,
reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (gp9lphox and p47phox), nuclear factor-κB (NF-κB), and
inhibitor of κB (IκB) were measured by Western blotting. Results Injection of Aβ1-40 caused a significant increase in the
expressions of RAGE, gp9lphox, p47phox, phospho-p47phox, phospho-IκBα, NF-κB and phospho-NF-κB in rat hippocampus but
decreased the level of IκBα. Aβ1-40 injection also resulted in a significantly increased content of ROS in the hippocampus of the
rats. Conclusion Aβ up-regulates the expression of RAGE in rat hippocampus via NADPH/ ROS/NF-κB signaling pathway.