黄芪多糖对AD大鼠模型氧化应激反应与Wnt信号通路的影响

EFFECTS OF ASTRAGALUS POLYSACCHARIDE ON OXIDATIVE STRESS RESPONSE AND WNT SIGNALING PATHWAY OF AD RAT MODEL

目的探究黄芪多糖(APS)对阿尔茨海默病(AD)大鼠模型氧化应激反应与Wnt信号通路的影响。方法雄性SD大鼠随机分为空白对照组、假手术组、模型组、APS组,每组10只。后两组在大鼠双侧海马CA1区立体定向注射β淀粉样蛋白(Aβ)造AD模型,假手术组注射等量生理盐水,正常对照组不做处理。造模1个月后APS组予以400 mg/kg APS灌胃,1次/d,其他组予以等量生理盐水灌胃,均连续治疗60 d。治疗后,测定各组大鼠脑海马组织丙二醛(MDA)及超氧化物歧化酶(SOD)一抗、过氧化氢酶(CAT)一抗活性;观察APS对AD大鼠海马Tau蛋白上部位磷酸化位点及Aβ前体APP水平的影响,检测β-联蛋白(β-catenin)和糖原合成激酶3β(GSK-3β)水平及Aβ沉积程度。结果与模型组比较,APS组大鼠MDA含量明显降低(P<0.05),SOD及CAT活性明显升高(P<0.05)。模型组大鼠脑皮质区Aβ沉积明显,可见细胞间隙呈褐色改变,而APS组大鼠脑皮质区Aβ沉积明显降低。与模型组比较,APS组大鼠Tau磷酸化水平及GSK-3β活性降低(P<0.05),β-eatenin蛋白表达量升高(P<0.05)。结论黄芪多糖能明显改善AD大鼠氧化应激反应,并可能通过激活Wnt信号通路抑制Aβ蛋白引起的神经毒性,发挥神经保护作用。

Objective To investigate the effects of astragalus polysaccharide(APS)on oxidative stress response and Wnt signaling pathway of Alzheimer’s disease(AD)rat model.Methods Male SD rats were randomly divided into blank control group,sham operation group,model group and APS group,10 rats in eachgroup.In the latter two groups,stereotactic injection ofβ-amyloid protein(Aβ)was performed in bilateral hippocampal CA1 region of rats to establish AD model.The sham operation group was injected with same amount of normal saline.The normal control group was not treated.At 1 month after modeling,APS group was given intragastric administration of 400 mg/kg APS,once a day.And the other groups were given same amount of normal saline for 60 days.After treatment,the contents of MDA and SOD and CAT activities in the hippocampus of each group were detected.The effects of APS on phosphorylation sites of Tau protein and APP levels of Aβprecursor in AD rats hippocampus were observed.Theβ-catenin(β-catenin)and glycogen synthase kinase3β(GSK-3β)levels,and Aβdeposition degree were detected.Results Compared with model group,MDA content in APS group significantly decreased(P<0.05),while SOD and CAT activities significantly increased(P<0.05).The Aβdeposition was obvious at cerebral cortex in model group.There was brown change in intercellular space.The Aβdeposition at cerebral cortex in APS group significantly reduced.Compared with model group,tau phosphorylation level and GSK-3 activity in APS group decreased(P<0.05),whileβ-eatenin protein expression quantity increased(P<0.05).Conclusion Astragalus polysaccharide can significantly improve oxidative stress response of AD rats,which can inhibit neurotoxicity induced by Aβprotein by activating Wnt signaling pathway,and exert neuroprotective effects.