大黄酚通过拮抗Aβ_(1-42)诱导的氧化应激改善大鼠空间记忆能力（英文）

Chrysophanol ameliorates spatial memory ability of rats by inhibiting Aβ_(1-42)-induced oxidative stress

目的:检测大黄酚是否能够拮抗β-淀粉样蛋白1-42(Aβ_(1-42))所致大鼠学习记忆损害以及可能的抗氧化应激机制。方法:Wistar雄性大鼠(n=60)分为对照组、Aβ_(1-42)组、大黄酚组及大黄酚(1、10和100 mg/kg)+Aβ_(1-42)等6组。侧脑室注射Aβ_(1-42)建立阿尔茨海默病模型,单次或多次给予不同浓度(1、10和100 mg/kg)大黄酚处理5 d后进行Y迷宫实验、旷场实验和Morris水迷宫实验检测大鼠的学习和记忆能力。行为学实验结束后,取出各组大鼠海马组织,利用ELISA法检测不同处理组海马组织中丙二醛(MDA)的含量及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶(CAT)的活性。结果:Y迷宫实验和水迷宫实验结果表明,多次注射不同浓度的大黄酚(每天1次,连用5 d)能够剂量依赖性拮抗Aβ_(1-42)造成的认知功能缺损。而且,多次注射不同浓度的大黄酚能够有效拮抗Aβ_(1-42)激发的MDA含量升高以及抗氧化酶(SOD、GSH-Px和CAT)的降低。结论:多次重复给予大黄酚可以减轻Aβ_(1-42)诱导的大鼠认知功能缺陷,这一作用可能是通过调节抗氧化酶的活性来实现的。

AIM： To investigate whether chrysophanol alleviates amyloid β-protein（ Aβ）-induced cognitive dysfunction and the underlying antioxidative mechanism. METHODS： Adult male Wistar rats（ 230 ～ 250 g） were randomly divided into control group,Aβ_（1-42） group,chrysophanol group,and Aβ_（1-42）＋ chrysophanol（ 1,10 and 100 mg/kg）groups. Aβ_（1-42） was delivered by intracerebroventricular injection under the guidence of a brain stereotaxic apparatus. Ymaze test,open-field test and Morris water maze test were performed 1 week after Aβ_（1-42） injection to evaluate the ability of rat spacial learning and memory. Chrysophanol was intraperitoneally injected once daily for 5 consecutive days. After the behavioral tests,the animals were sacrificed immediately by decapitation,and the hippocampus were collected. The malondialdehyde（ MDA） content and the activity of superoxide dismutase（ SOD）,glutathione peroxidase（ GSH-Px） and catalase（ CAT） in the hippocampus were measured. RESULTS： Multiple（ 7 consecutive days,once daily） but not single（ once a day） chrysophanol treatment at 1,10 and 100 mg/kg effectively prevented Aβ_（1-42）-induced cognitive function deficits in a dose-dependent manner as shown by Y-maze test and Morris water maze test. Moreover,the Aβ_（1-42）-induced increase in MDA content and decrease in the activity of antioxidant enzymes（ SOD,GSH-Px and CAT） in the hippocampus of the rats were also attenuated by multiple chrysophanol treatment. CONCLUSION： Repeated chrysophanol treatment attenuates Aβ_（1-42）-induced cognitive deficits and synaptic plasticity dysfunction,and the mechanisms underlying the neuroprotective effects are likely due to its antioxidant activity.