黄芪多糖对阿尔茨海默病模型大鼠的疗效及其作用机制研究

目的 探讨黄芪多糖(Astragalus polysaccharide,APS)对大鼠阿尔茨海默病(Alzheimer's disease,AD)模型大鼠的疗效及其作用机制。方法 将48只SPF大鼠随机分成3组,每组各16只:对照组、模型组和治疗组; 模型组和APS治疗组采用Aβ_25-35(80 pmol/μL)双侧脑室注射大鼠诱导AD模型,模型制备成功后APS治疗组给予APS(400 mg/kg)灌胃,1次/d,连续60 d; 对照组和模型组给予等剂量生理盐水灌胃,1次/d,连续60 d; 治疗结束后采用水迷宫实验(MWM)评价各组大鼠定位航行能力和记忆能力; MWM实验结束后处死各组大鼠获取海马行常规HE染色观察病理组织学变化,行Western-blot检测海马组织中淀粉样蛋白(amyloid peptide protein,APP)、β-淀粉样蛋白(amyloid peptide-β,Aβ)、磷酸化微管相关蛋白(Phosphorylation tau,p-tau)、糖原合成酶激酶3β(glycogen synthase kinase 3beta,GSK3)和蛋白磷酸酯酶2A(protein phosphatase 2A,PP2A)等蛋白的表达水平。结果 与模型组相比,APS治疗组可显著改善大鼠的定位航行能力(P<0.01)与学习记忆能力(P<0.01); HE染色表明APS治疗组可修复Aβ_25-35所致的大鼠海马损伤; Western-blot表明与模型组相比,ASP治疗组APP,Aβ,p-tau,GSK3β和BACE1的蛋白水平下调(P<0.05,P<0.01,P<0.01,P<0.05,P<0.01),PP2A 的蛋白水平上调(P<0.05)。结论 APS对Aβ25-35所致的AD具有保护作用。

Effect of astragalus polysaccharide and mechanism on Alzheimer 's disease rats

ObjectiveTo discuss the effect and mechanism of astragalus polysaccharide(APS)on Alzheimer's disease(AD)rats.Methods Forty-eight SPF rats were randomly divided into three groups named the control group, the model group and the treatment group. The model of AD was induced by injection of Aβ25-35(80 pmol/μL)in APS group and model group. Rats in the APS group were treated with APS(400 mg/kg)orally once a day for 60 days, while the control group and the model group were given equal-dose saline by gavage once a day for 60 days. After treatment had been carried out, the ability of navigation and memory was evaluated by water maze test(MWM). And then, rats in all groups were sacrificed to obtain the hippocampus. HE staining was used to observe the histopathological changes, expression levels of APP,Aβ,p-tau,GSK3β,BACE1and PP2A protein in hippocampus were detected by western blot.Results Compared with the model group, APS could significantly improve the ability of learning and memory(P<0.01)and improve the ability of locating navigation(P<0.01). The consequences of HE staining showed that the rat hippocampus injury induced by Aβ25-35 could be repaired by APS treatment. Western blot analysis showed that the levels of APP, Aβ, p-tau, GSK3β and BACE1 were down-regulated, while the protein level of PP2A was up-regulated(P<0.05)in ASP group which compared with the model group(P<0.05, P<0.01, P<0.01).Conclusion APS had a protective effect on Aβ25-35-induced AD model, and it was supposed to be a strategy for the prevention and treatment of AD.