香菇多糖对阿尔茨海默病大鼠海马组织的影响

Effect of lentinan polysaccharides on hippocampus in Alzheimer＇s disease rats

目的 研究香菇多糖（lentinan polysaccharide,LPS）对阿尔茨海默病（Alzheimer＇s disease,AD）模型大鼠中海马组织的影响,为AD的治疗提供新的策略。方法 将96只SPF大鼠随机分成对照组、模型组、LPS低浓度治疗组（200 mg/kg）、LPS中浓度治疗组（400 mg/kg）、LPS高浓度治疗组（600 mg/kg）和阳性药物对照组（吡拉西坦600 mg/kg）6组,每组16只。采用Aβ25-35（80 pmol/μL）双侧脑室注射建模,模型制备成功后,各治疗组分别给予相应浓度药物灌胃,对照组和模型组给予等剂量生理盐水灌胃,1天1次,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,处死大鼠获取各组海马体组织,行常规HE染色观察病理组织学变化,Western blot检测海马组织中肿瘤坏死因子-α转化蛋白（TNF-αconverting enzyme,TACE）、β-淀粉样蛋白（amyloid peptide-β,Aβ）、β-淀粉样前体蛋白裂解酶1（β-site APP cleaving enzyme 1,BACE）和蛋白磷酸酯酶2A（protein phosphatase 2A,PP2A）蛋白的表达。结果 与模型组相比,LPS高剂量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染色结果表明,LPS高剂量治疗组可修复Aβ25-35所致的大鼠海马损伤。Western blot结果表明,与模型组相比,LPS治疗组中Aβ和BACE1的蛋白水平下调,PP2A和TACE的蛋白水平上调。结论 LPS对Aβ25-35所致的AD海马组织具有保护作用,可望成为一种治疗AD的新策略。

Objective To evaluate the effect of lentinan polysaccharide （LPS） on Alzheimer＇s disease （AD） rats, and providing a new idea for prevention and treatment of Alzheimer＇s disease （AD）.Methods 96 SPF rats were randomly divided into control group, model group, LPS low dose-treated group, LPS middle dose-treated group, LPS high dose-treated group and positive control group（piracetam treated）, each had 16 rats.The model of AD was induced by injection of Aβ25-35（80 pmol/μL）, rats in four treatment groups were treated with LPS （200 mg/kg）, LPS （400 mg/kg）, LPS （600 mg/kg） and piracetam（600 mg/kg） orally once a day for 60 days while control group and model group were given equal-dose saline.After treatment, the ability of navigation and memory were 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, the expressions of TACE,Aβ,BACE1 and PP2A protein in hippocampus were detected by Western blot.Results Compared with the model group, high dose LPS could significantly improve the ability of learning and memory （P〈0.01） and improve the ability of locating navigation （P〈0.01）.HE staining results showed that LPS treatment could repair the rat hippocampus injury induced by Aβ25-35 .Western blot analysis showed that the levels of Aβ, and BACE1 were down-regulated in LPS group compared with the model group, while the protein level of PP2A and TACE was up-regulated.Conclusion LPS has a protective effect on Aβ25 -35 induced AD model, and it is expected to be a strategy for treatment of AD .