Shenrong Mixture's Anti-A?_25-35-induced Tau Protein Phosphorylation And Its Related Mechanism In Alzheimer's Disease Mouse Model

Objective:To research the effect of Shenrong Mixture on the expression of P-tau in brain tissues and evaluated the possible mechanism.Materials and Methods:The mice were randomly select 16 mice into sham group and injected in the dose of 3?l normal saline into the lateral ventricle,the rest of mice were injected in the dose of 3?l A?_25-35?1mg/ml?into the lateral ventricle.When molding finished,put the mice back.And observe the mice'condition in the next day.Put the molding mice into model group,donepezil 1.3mg/kg control group,Shenrong Mixture 6.5g/kg group,Shenrong Mixture 13g/kg group,Shenrong26g/kg group randomly.And The mice were dosed last for 21 days.The Y-maze behavioral test was performed one hour after the end of the 15-day administration,and then the morris water maze behavior test was lasted for 6 days.Some of the mice were perfused and fixed and the tissue was taken for the HE staining and immunohistochemistry.The other part was taken out of the brain tissue for Western Blot test,such astau-5?P-tau?Ser 404?Thr181?Thr231?Ser396??PI3K?P-PI3K?AKT?P-AKT?GSK3??P-GSK3??PP2A?PKA?ERK.To evaluate the pharmacodynamics of Shenrong Mixture on the deposition of A?deposition and abnormal phosphorylation of tau protein in AD model mice.Results:1?Shenrong Mixture improve the learning and memory ability of AD model mice and have obviously protect effects on neurons.2?Shenrong Mixture can activate the PI3K/AKT/GSK3?and PP2A/PKA-ERK pathway to reduce the tau abnormal phosphorylation degree.Conclusion:1?Shenrong Mixture can reduce A?_25-355-35 induced neuronal damage,improving the capability of learning and memory in AD model mice.2?Shenrong Mixture can activate the PI3K/AKT/GSK3?pathway to reduce the tau abnormal phosphorylation level,in according to improve AD symptom.3?Shenrong Mixture can activate PP2A/PKA-ERK pathway to balance the tau phosphorylation level.