丹皮酚通过激活Nrf2/HO-1通路改善阿尔茨海默病大鼠海马组织的氧化应激损伤

Paeonol improves oxidative stress damage in hippocampus of rats with Alzheimer’s disease through activating Nrf2/HO-1 pathway

目的探讨丹皮酚对阿尔茨海默病(AD)大鼠学习记忆能力,海马氧化应激水平及转录因子NF-E2相关因子2/血红素氧合酶-1(Nrf2/HO-1)表达的影响。方法Morris水迷宫评价大鼠行为学,分光光度法检测氧化应激参数,Western blot测定Nrf2、HO-1蛋白表达。结果与假手术组相比,双侧海马内注射β-淀粉样蛋白1-42(Aβ1-42)能够诱导MDA水平明显升高,SOD活力,胞核内Nrf2、HO-1蛋白水平显著降低(P<0.05)。与AD组比较,丹皮酚能显著改善学习记忆能力,同时海马中氧化应激水平明显下降,Nrf2、HO-1蛋白水平显著升高(P<0.05)。结论Nrf2/HO-1通路下调参与了Aβ诱导的氧化应激损伤,丹皮酚可通过激活该通路对AD起到神经保护作用。

Objective To investigate the effects of paeonol on learning ability and memory,oxidative stress and expression of Nrf2/HO-1 pathway in hippocampus of Alzheimer’s disease(AD)rats.Methods The learning ability and memory of rats was evaluated by Morris water maze.The oxidative stress parameters in hippocampus were detected by spectrophotometry.The expression of Nuclear factor-erythroid2-related factor 2(Nrf2)and Heme oxygenase-1(HO-1)protein in hippocampus was determined by western blot.Results Compared with the sham group,hippocampal beta-amyloid(Aβ1-42)injection resulted in increased malondialdehyde(MDA)level,the significantly decreased superoxide dismutase(SOD)activity and the decreased expression of nuclear Nrf2,HO-1 protein in the hippocampus of the AD group(P<0.05).Compared with the AD group,paeonol can ameliorate the learning ability and memory of rats suffering Aβ1-42 injected,significantly decrease the oxidative stress level in the hippocampus and elevate the protein levels of Nrf2 and HO-1(P<0.05).Conclusions The downregulation of Nrf2/HO-1 pathway in hippocampus is involved in Aβ-induced oxidative stress damage.Paeonol can be neuroprotective by activating this pathway.