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

摘要

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 (gp91phox and p47phox),nuclear factor-κB (NF-κB),and inhibitor of κB (IκB) were measured by Western blotting.Results Injection of A1～40 caused a significant increase in the expressions of RAGE,gp91phox,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.%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(gp91phox及p47phox亚基)、核因子-κb(NF-1κB)、NF-κB抑制蛋白(IκB)的表达变化,利用流式细胞仅检测大鼠海马组织活性氧(ROS)的变化.结果 海马注射Aβ1～403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),gp91phox、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阿引起海马组织RAGE的表达升高,NADPH氧化酶/ROS/NF-κB信号通路可能在Aβ秀导海马神经元RAGE的表达过程中发挥重要作用.