欧前胡素对Aβ_(1-42)致阿尔茨海默病模型小鼠海马组织氧化应激反应的影响  

Effects of Imperatorin on Oxidative Stress Response in the Hippocampus of the Mouse Model of Alzheimer's Disease Induced by Aβ_(1-42)

作　　者：余盈[1] 于罡 何蔚[1] YU Ying;YU Gang;HE Wei(Department of Pharmacology,Gannan Medical College,Key Laboratory of Cerebrovascular Pharmacology of Jiangxi Province,Ganzhou 341000,China)

机构地区：[1]赣南医学院药理学教研室江西省脑血管药理重点实验室,赣州341000

出　　处：《天然产物研究与开发》2018年第8期1423-1426,1409,共5页Natural Product Research and Development

基　　金：江西省研究生创新专项(YC2017-S419);江西省卫生计生委中医药科技计划(2015B045)

摘　　要：研究欧前胡素对Aβ_(1-42)致阿尔茨海默病(Alzheimer’s disease,AD)模型小鼠海马组织氧化应激反应的影响及作用机制。脑室内注射Aβ_(1-42)制备小鼠AD模型,欧前胡素2.5 mg/kg和5.0 mg/kg在手术后当天开始腹腔注射给药,1次/d,连续给药13天。第14天,分离小鼠海马组织,测定氧化应激反应指标ROS、MDA、SOD、TAOC、GSH-Px、CAT、NO和iNOS,Western Blot检测海马组织核蛋白中Nrf-2的蛋白表达。研究显示,欧前胡素可降低海马组织中ROS、MDA和NO的含量和抑制iNOS的活性,增加SOD、GSH-Px、CAT的活力和T-AOC的水平,上调Nrf2的蛋白表达。研究结果提示,欧前胡素可减轻Aβ_(1-42)致小鼠AD后海马组织氧化应激反应,其机制同欧前胡素抑制活性氧自由基的产生和抑制脂质过氧化反应及增强机体的抗氧化能力有关。The aim of this study was to investigate the effects of imperatorin on oxidative stress response in the hippocampus in the mouse model of Alzheimer’s disease(AD)induced by intracerebroventricular injection of Aβ1-42.Imperatorin(2.5 and 5.0 mg/kg)was injected by intraperitoneally once a day for 13 consecutive days from the day of surgery.The levels of reactive oxygen species(ROS),malondialdehyde(MDA),total antioxidant capacity(T-AOC),nitric oxide(NO)and the activities of inducible nitric oxide synthase(iNOS),superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px)in the hippocampus were determined,and the expression of nuclear factor erythroid 2-related factor 2(Nrf2)protein was detected by western blot.The results showed that imperatorin significantly reduced ROS,MDA,and NO contents and iNOS activities,increased levels of SOD,CAT,GSH-Px and T-AOC,and up-regurated the protein expression of Nrf2 as compared with AD model group.Our study suggests that imperatorin treatment can significantly attenuate oxidative stress injury in the Aβ1-42 induced AD mice,and the mechanisms may be associated with the inhibition of production of active oxygen radicals and lipid peroxides,and enhancement of the antioxidant capacity in the mice.

关 键 词：欧前胡素 AΒ1-42 阿尔茨海默病 海马 氧化应激 

分 类 号：R338.64[医药卫生—人体生理学] R965[医药卫生—基础医学]