Advanced glycation end products (AGEs) are a group of modified proteins and/or lipids with damaging potential. AGEs-RAGE pathway plays a critical role to induce neurodegenerative encephalopathy. Statins can reduce the expression of AGEs-induced AGEs receptor (RAGE) in the aorta. It is not clear whether statins have potential benefits on AGEs-induced cognitive impairment. In this study, the effects of atorvastatin (ATV) on inflammation and oxidation stress in the cerebral cortex were investigated, and the underlying mechanisms were explored. Apolipoprotein E (ApoE)^−/− male mice were divided into four groups: control, AGEs, AGEs + ALT711 (Alagebrium chloride) and AGEs + ATV. β-amyloid (Aβ) formation in the cerebral cortex was assessed through Congo red staining and the functional state of neurons was evaluated by Nissl’s staining. Immunostaining was performed to assess the accumulation of AGEs in the cerebral cortex. The expressions of mRNA and protein of RAGE, Nuclear factor kappa B (NF-κB) p65 and Nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) p47phox were detected by real-time polymerase chain reaction (PCR) and western blot. There were significant increases in AGEs deposit, Aβ formation, and the expressions of RAGE, NF-κB p65, and NADPH oxidase p47phox, and a decrease Nissl body in AGEs group compared with control group. ALT711 group recovered above change compared with AGEs group. Atorvastatin reduced Aβ formation and suppressed AGEs-induced expressions of NF-κB p65 and NADPH oxidase p47phox. Atorvastatin has little effects on AGEs deposit and RAGE expressions. Atorvastatin alleviates AGEs-induced neuronal impairment by alleviating inflammation and oxidative stress via inhibiting NADPH oxidase-NF-κB pathway.

高级糖基化终产物（AGEs）是一组具有潜在破坏力的修饰蛋白质和/或脂质。AGEs-RAGE途径在诱导神经变性脑病中起关键作用。他汀类药物可以减少AGEs诱导的AGEs受体（RAGE）在主动脉中的表达。他汀类药物是否对AGEs引起的认知障碍具有潜在的益处尚不清楚。本研究探讨了阿托伐他汀（ATV）对大脑皮质炎症和氧化应激的影响，并探讨了其潜在机制。载脂蛋白E（ApoE）^-/-雄性小鼠分为四组：对照组，AGEs，AGEs + ALT711（氯化阿勒溴铵）和AGEs + ATV。通过刚果红染色评估大脑皮层中的β-淀粉样蛋白（Aβ）的形成，并通过尼氏染色评估神经元的功能状态。进行免疫染色以评估AGEs在大脑皮层中的积累。实时聚合酶链反应（PCR）和Western blot检测RAGE，核因子κB（NF-κB）p65和烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH氧化酶）p47phox的mRNA和蛋白表达。与对照组相比，AGEs组的AGEs沉积，Aβ形成，RAGE，NF-κBp65和NADPH氧化酶p47phox的表达显着增加，而Nissl体减少。与AGEs组相比，ALT711组的恢复高于变化。阿托伐他汀可减少Aβ的形成并抑制AGEs诱导的NF-κBp65和NADPH氧化酶p47phox的表达。阿托伐他汀对AGEs沉积和RAGE表达几乎没有影响。阿托伐他汀通过抑制NADPH氧化酶-NF-κB途径减轻炎症和氧化应激，从而减轻AGEs诱导的神经元损伤。