阿里红多糖对阿尔茨海默症小鼠认知功能的作用机制研究

Effects of Fomes officinalis Ames polysaccharides a and b components on the behavior of Alzheimer’s disease mice

目的考察阿里红多糖(FOPS)改善淀粉样前体/早老素(APP/PS1)阿尔茨海默症小鼠的认知功能及潜在机制。方法C57BL/6J雄性小鼠作正常组;根据体重将APP/PS1双转基因雄性小鼠随机分为4组:模型组、对照组、FOPS-a实验组和FOPS-b实验组,每组8只。模型组正常饲养,对照组给予0.65 mg·kg^(-1)盐酸多哌奈齐,FOPS-a实验组给予60 mg·kg^(-1) FOPS-a,FOPS-b实验组给予60 mg·kg^(-1) FOPS-b,灌胃给药;qd,连续给药3个月。用Morris水迷宫实验检测小鼠学习记忆能力,实时荧光定量-聚合酶链反应法测定海马区糖原合成酶激酶-3(GSK3α)、淀粉样前体蛋白(APP)、β淀粉样蛋白(Aβ)基因转录情况,蛋白质印迹法检测GSK3Α、APP、Aβ_(1-42)、早老素(PS-1)蛋白的表达。结果模型组、正常组、对照组、FOPS-a组、FOPS-b剂量组第4天逃避潜伏期分别为(48.29±10.49),(27.36±17.25)(28.91±20.31),(23.21±17.60)和(24.25±16.40)s;这5组的GSK3αmRNA转录水平分别为7.17±0.46,1.03±0.27,3.11±0.45,4.15±0.67和4.41±0.43;这5组APP mRNA转录水平分别为1.12±0.04,0.36±0.02,0.40±0.04,0.45±0.07和0.50±0.08;AβmRNA转录水平分别为1.12±0.04,0.24±0.10,0.44±0.06,0.45±0.07和0.50±0.08;蛋白结果的趋势与基因一致。上述指标,模型组与正常组比较、实验组与模型组相比,差异均有统计学意义(均P<0.05)。结论阿里红多糖组分能够改善APP/PS-1转基因小鼠学习记忆障碍,其机制可能与抑制GSK3α,APP,Aβ_(1-42),PS-1蛋白表达和降低海马区Aβ_(1-42)沉积有关。

Objective To investigate the effect of Fomes officinalis Ames polysaccharide(FOPS)on cognitive function and its potential mechanism in amyloid precursor/presenilin(APP/PS1)mice with Alzheimer’s disease.Methods C57 BL/6 J male mice were used as normal group;according to body weight,APP/PS1 double transgenic male mice were randomly divided into 4 groups:model group,control group,FOPS-a experimental group and FOPS-b experimental group,each group has 8 male mice.The model group was fed normally,the control group was given 0.65 mg·kg^(-1) dopenezil hydrochloride,the FOPS-a experimental group was given 60 mg·kg^(-1) FOPS-a,the FOPS-b experimental group was given 60 mg·kg^(-1) FOPS-b,oral administration;qd,continuous administration for 3 months.Morris water maze was used to detect the changes in the learning and memory ability of mice,the HE method was used to detect the pathological changes in the hippocampus of each group of mice,the real-time fluorescent quantitative polymerase chain eaction method was used to determine the transcription of glycogen synthase kinase-3(GSK3α),amyloid precursor protein(APP),βamyloid protein(Aβ)mRNAs in the hippocampus,and the Western blot method was used to investigate GSK3α、APP、Aβ_(1-42)、presenilin 1(PS-1)protein expression.Results Model group,normal group,control group,FOPS-a groups,FOPS-b groups,the escape latency on day 4 was(48.29±10.49),(27.36±17.25)(28.91±20.31),(23.21±17.60),and(24.25±16.40)s;the GSK3αtranscription levels of mRNA in these 4 groups were 7.17±0.46,1.03±0.27,3.11±0.45,4.15±0.67,and 4.41±0.43,respectively;APP mRNA transcription levels were 1.12±0.04,0.36±0.02,0.40±0.04,0.45±0.07,and 0.50±0.08;AβmRNA transcription levels were 1.12±0.04,0.24±0.10,0.44±0.06,0.45±0.07,and 0.50±0.08.The trend of protein results is consistent with that of gene.Conclusion For the above indicators,there were statistically significant differences between the model group and the normal group,and between the experimental group and the model group(all P<0.05).Conclusion The mechanism may be related to the inhibition of GSK3α,APP,Aβ_(1-42),PS-1 protein expression and the reduction of Aβ_(1-42) deposition in the hippocampus.