Effect Of Danggui Shaoyao San On Intestinal Flora Of APP/PSN Alzheimer's Disease Model Mice And Molecular Mechanism

Objective:To analyze the intestinal flora of APP/PSN Alzheimer's disease(AD)model mice and C57BL/6(B6)mice,and to study the effects of Danggui Shaoyao San(DSS)on differential intestinal flora.To explore the possible effects of differential flora on AD mice.By detecting the biochemical indicators,A? protein content and behavioral changes associated with AD,the detection indicators and learning function of AD mice were evaluated after DSS treatment.Methods:Forty APP/PSN double-transgenic AD model mice were randomly divided into model group,Danggui Shaoyao San low,medium and high dose groups,10 rats in each group,and another 10 B6 mice were used as the control group.DSS was administered to AD mice in the treatment group for 2 months.The model group and the control group were replaced with normal saline.The spatial learning and memory of each group were detected by Morris water maze video tracking and analysis system.The brains of each group were detected by Western Blot.The expression level of A?1-42 protein in hippocampus was labeled by immunofluorescence to A?1-42 protein in mouse CA1 region.16 S rRNA gene high-throughput sequencing method was used to detect the intestinal flora and intestinal flora community distribution structure and species relatives of AD and B6 mice with different levels of phylum,class,order,family,genus and species.Abundance;the concentration of serum serotonin and ?-aminobutyric acid in each group of mice was determined by ELISA.Results:(1)The spatial learning ability of mice in the model group was worse than that in the control group.After DSS treatment,the spatial learning ability of AD miceimproved.(2)The expression of A?1-42 protein in the hippocampus of the model group was up-regulated compared with the control group.DSS down-regulated the expression of A?1-42 protein in the hippocampus of AD mice in a dose-dependent manner.(3)The density of A?1-42 protein in the CA1 region of the model group was higher than that of the control group.DSS could reduce the deposition of A?1-42 protein in the CA1 region of AD mice.(4)The abundance of De-fervation,?-proteobacteria,Campylobacter,Helicobacter pylori and mucinous bacteria in the model group were significantly increased compared with the control group,and the relative abundance of the species with significantly increased abundance of DSS decreased.And presented in a dose dependent manner.The abundance of Lactobacillus was significantly reduced in the model group compared with the control group,and DSS increased the relative abundance of Lactobacillus.(5)The serum 5-HT and GABA concentrations in the model group were lower than those in the control group,and the 5-HT in the serum could be obtained after DSS treatment.The concentration of GABA has increased to varying degrees.Conclusion:1.DSS may improve the expression of A? protein in APP/PSN double transgenic AD mouse model by increasing 5-HT in serum.2.DSS may have a positive effect on the learning and memory of hippocampus by increasing the serum GABA concentration in the APP/PSN double-transgenic AD mouse model.3.DSS may increase the abundance of Lactobacillus family and reduce the relative abundance of mucinous bacteria in Helicobacter pylori and Deferobacteria in Campylobacter variabilis.APP/PSN double transgenic AD model mice Have a positive impact.mucinous bacteria.