Study On The Effect And Mechanism Of Shenqi Xingnao Fang On Improving The Learning And Memory Ability Of AD Mouse Model Based On The Pathogenesis Of "toxic Damage To Brain Collaterals

Objective:This study was based on the Theory of "Toxin Hurts Brain Collaterals" and observed that Shenqi Xingnao extract had three different effects on scopolamine-induced dementia mice,D-galactose-induced dementia mice,and APP/PS1 double-transgenic dementia mice.The effect of learning and memory function in mice with type 1 dementia is to explore the possible pharmacological effects and mechanisms of Shenqi Xingnao Extract on cholinergic,neurotrophic and amyloid protein precipitation.Methods:(1)Effect of Shenqi Xingnao Extract on mice model of memory impairment caused by scopolamine:111 ICR mice,male,were randomly divided into control group,control group,Shenqi Xingnao large dose group,model group,model+Shenqi Xingnao low-dose group,model+Shennao Xingnao middle-dose group,model+Shenqi Xingnao high-dose group,model+Donepezil group were a total of seven groups.A model of memory impairment in mice was induced by intraperitoneal injection of scopolamine and the model was established by intraperitoneal injection 20 minutes before each behavior.Morris water maze and object recognition behaviors were detected on the 15th day after modeling.The brains of mice were taken after the behavior was completed.Western blot was used to detect the content of AchE and ChAT in the cortex and hippocampus of mice.(2)Effect of Shenqi Xingnao extract on mice model of Alzheimer’s disease induced by D-galactose:111 ICR mice,male,were randomly divided into control group,control group.Shenqi Xingnao large dose group,model group.There were 7 groups:model+Shenqi Xingnao low dose group,model+Shenqi Xingnao middle dose group,model+Shenqi Xingnao high dose group,and model+Donepezil group.AD-galactose solution(100 mg/kg)was injected subcutaneously into the back of the neck and injected once a day for a total of 60 days to make a mold.Shenqi Xingnao Extract was continuously administered for 60 days.Morris water maze and object recognition behavioral tests were performed.After the completion of behavior,fresh materials and perfusion were performed.Western blot was used to detect NGF,NueN and synapse-related proteins in mouse cortex and hippocampus.Immunohistochemistry was used to detect the mice.Hippocampus NGF expression.(3)Effect of Shenqi Xingnao extract on APP/PS1 double transgenic mouse model:119 control group,control group and Shenqi Xingnao group.The medium dose group,the model group,the model+Shenqi Xingnao low dose group,the model+Shenqi Xingnao middle dose group,the model+Shenqi Xingnao high dose group,and the model+Donepezil group were a total of seven groups.Shenqi Xingnao Extract was continuously administered intragastrically for 82 days,followed by Morris water maze and object recognition behavior test.At the end of behavior,fresh materials and perfusion were performed.Western blot was used to detect BACE1,SAPPβ,IDE,Ser396,Tyr216,NueN and synapse-related proteins in mouse cortex and hippocampus.The expression of Aβ in hippocampus of mice was detected by immunohistochemistry.Result:(1)The results showed that Shenqi Xingnao Extract could significantly reduce the escaping latency of scopolamine-induced learning disability mice model in the Morris water maze test for 14 days.The discrimination index can reduce the content of acetylcholinesterase in the cerebral cortex and hippocampus of model mice,which helps to slow the degradation of acetylcholine and increase the content of acetylcholine in the brain.(2)Shenqi Xingnao extract can significantly shorten the escape latency of D-galactose mouse model in Morris water maze test,increase the discrimination index of model mice in object recognition test,and can increase the cerebral cortex of model mice.Expression of neuron marker protein NeuN in hippocampus and content of nerve growth factor(NGF).(3)The continuous intragastric administration of Shenqi Xingnao Extract for 82 days can shorten the escape latency of the model mice in the Morris water maze test,and increase the discrimination index of the model mice in the object recognition test.Increase the number of surviving neurons in the brain;Decrease the expression of SAPPβ and β-secretase(BACE1)in the Aβ generation pathway;Increase the expression of the insulin degradation enzyme(IDE)in the Aβ degradation pathway;Reduce the hyperphosphorylation and sugar of the Tau protein in the Ser396 locus Prokaryotic kinase 3-beta(GSK3beta)phosphorylation at the Tyr216 site.The results showed that Shenqi Xingnao extract can reduce Aβ content by inhibiting Aβproduction pathway and enhancing Aβ degradation pathway,and can inhibit Tau protein hyperphosphorylation by reducing GSK3β activity and promote neuron survival,Thus improving AD model mice cognitive dysfunction.Conclusion:The above results show that Shenqi Xingnao extract can significantly improve the cholinergic and neurological impairment of Tau hyperphosphorylation and cognitive impairment in patients with memory impairment and multiple dementia models.(1)In a mouse model of memory impairment caused by scopolamine,Shenqi Xingnao Extract can improve learning and memory ability in scopolamine-induced memory impairment mice.Its possible mechanism of action is related to the decrease of acetylcholinesterase content,thus increasing the synthesis of ACh.(2)In the mouse model of Alzheimer’s disease induced by D-galactose,the mechanism of Shenqi Xingnao extract may be related to the increase of NGF content and the increase of neuron survival.(3)In the AD mouse model of APP/PS1 double-transgenic AD mouse model,themechanism of action of Shenqi Xingnao extract may be mainly to reduce Aβ content by inhibiting the production pathway and enhancing degradation pathway of Aβ.And by reducing activity of GSK3β to inhibit Tau protein hyperphosphorylation,and promote neuron survival,so as to achieve the role of improving cognitive impairment.