摘要
目的探讨核因子红系2相关因子2(nuclear factor erythroid derived 2-related factor 2,Nrf2)激活剂莱菔硫烷(sulforaphane,SFP)对糖基化终末产物(advanced glycation products,AGEs)诱导大鼠海马氧化应激损伤和炎症反应的保护作用及其机制。方法 40只Wistar大鼠被随机分为4组:生理盐水组(Control组)、SFP对照组、AGEs组和SFP组,给予AGEs组及SFP组大鼠双侧海马立体定向注射AGEs 5μL,造成AGEs组大鼠海马损伤,Control组及SFP对照组注射等量的生理盐水作为对照;造模前1周给予SFP组和SFP对照组大鼠5 mg·kg^(-1)·d^(-1)SFP腹腔注射,连续4周,AGEs组及Control组则同时给予同体积的生理盐水,造模结束后3周进行Morris水迷宫实验,测定大鼠逃避潜伏期及穿越平台次数;生化试剂盒检测大鼠海马超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)活性及丙二醛(MDA)水平;ELISA和Western blot法测定肿瘤坏死因子(TNF-α)以及白介素-1β(IL-1β)的表达水平。结果与Control组比较,AGEs组大鼠逃避潜伏期明显延长,穿越平台次数减少;海马氧化应激及炎症反应水平明显升高。SFP组较AGEs组逃避潜伏期显著降低、穿越平台次数明显增加;海马组织抗氧化系统水平升高;炎症因子表达减少。结论 SFP作为Nrf2激动剂,能改善AGEs引起的氧化应激和炎症反应,具有神经保护作用。
Objective To investigate the protective effects of the Nrf2 agonist sulforaphane（ SFP） on the advanced glycation products（ AGEs）-induced oxidative stress and neuroinflammation and the related mechanisms.Methods Fourty Wistar rats were randomly divided into 4 groups： normal control（ Control）,SFP control,AGEs and SFP groups. The bilateral hippocampus of rats in AGEs group and SFP group were injected AGEs to make injuring rat models. Control group and SFP group were intraperitoneal injected SFP 5 mg·kg^-1·d^-1 for 4 weeks before the animal models were produced,rats in AGEs and Control groups were injected equal volume of saline intraabominally.Morris water maze was used for testing escape latency and the number of crossing,related kits were used for detecting superoxide dismutase（ SOD） activity,glutathione peroxidase（ GSH-Px） activity,catalase（ CAT） and malondialdehyde（ MDA） content in the hippocampus,Western blot and enzyme-linked immunosorbent assay（ ELISA） were used for detecting the expression level of neuroinflammation factors,tumor necrosis factor（ TNF-α） and interleukin-1 beta（ IL-1β）. Results Compared with Control group,EL elevated,the number of crossings decreased,oxidative stress and neuroinflammatory cytokines levels increased significantly in AGEs induced injury rats. Compared with AGEs group,SFP obviously decreased EL,increased the number of crossings,increased SOD,GSH-Px,CAT activity and decreased MDA content,reduced the expression TNF-αand IL-1βin SFP group. Conclusion Nrf2 agonist SFP obviously improved cognitive function in AGEs induced brain injury,also improved the antioxidant ability,lowered inflammation levels in the brain,and had neuroprotective effect.
出处
《卒中与神经疾病》
2017年第5期388-392,共5页
Stroke and Nervous Diseases
基金
国家自然科学基金(基金编号为30971036)
山东省自然科学基金(基金编号为Y2008C13)
