The Effect Of Atorvastatin To AD Rat Model Through Inhibiting The NF-κB Signal Pathway And The Generation Of BACE1

Alzheimer’s disease (Alzheimer’s Disease, AD) is an age-related disease.the most common cause of disease is neurodegenerative disease anddementia.Worldwide every year nearly5million new-onset Alzheimer’sdisease patients.The disease is relatively Hidden.The mainly slow progressmemory loss,verbal,visual spatial and cognitive dysfunction.The late dailyliving in patients with serious loss and greatly increases economic burden andcare burden of the family and the social.However, the cause of ADpathological mechanisms are not yet fully understood, the current lack ofeffective drugs and methods.Therefore, the pathogenesis of AD is based on theresearch of new therapeutic targets and treatment has a very importantsignificance.In recent years, studies have shown that statins by inhibiting TNF-αreceptor, blocking the activation of NF-κB, may reduce the occurrence ofAD.NF-κB, a transcription factor of eukaryotic cells, is mainly involved in thebody’s defense response and tissue damage and stress and cell differentiationand apoptosis and the information transfer of the tumor growth inhibitionprocess.it exists in almost all cells,involved in multiple signal transductionpathway, is the focus of current research.Many studies have shown thatBACE1gene containing the NF-κB binding sites, the NF-κB activation canincrease the expression of the bace1in make bace1, so that the increase in Aβdeposition in turn lead to the AD.Objective:To discuss the relationship between NF-κB signal pathway,the generation of BACE1and the pathogenesis of Alzheimer disease anddiscuss the effect of Atorvastatin to Alzheimer disease (Alzheimerdisease,AD). Method:In this experiment, the rat model of AD was constructed byinjecting Aβ1-42to the rats’ bilateral hippocampal area using stereotaxisinstrument. Totally30male rats were divided into five groups, control group(6rats), sham operation group (6rats), model group (6rats), atorvastatin lowdose (8mg/kg) group (6rats), and atorvastatin high dose (16mg/kg) group (6rats).Morris water maze experiment was used to test the rats’ latency changesin positioning navigation and the frequency of crossing platform throughspace exploration, so as to observe the influence of atorvastatin at differentdoses on rats.Western-Blot method was used to detect the expression of NF-κB/P65and BACE1in the rats’ brain tissue, so as to confirmed the relationshipbetween AD and NF-κB/P65signal pathway, BACE1formation.Results:The results show that, experimental animal rats’ latency of fivedays was significantly decreased in the model group and the treatmentgroup.Compared with the control group, experimental animal rats in themodel group have significant barriers in spatial discrimination and thelearning and memory ability(P<0.01); compared with the modelgroup,experimental AD model rats in both the atorvastatin low dose group(8mg/kg) and atorvastatin high dose group (16mg/kg) showed greatimprovement in spatial discrimination and learning and memory ability, therewas a significant difference(P<0.05or P<0.01). At the same time, there is asignificant difference between the atorvastatin low dose group (8mg/kg) andatorvastatin high dose group (16mg/kg).Space exploration after jumpingnumber of changes with the change of the incubation period the sameexperiment.The expression of NF-κB/P65and BACE1protein detected byWestern-Blot method, compared with the control group, the difference wasstatistically significant in the model group(P<O.05), the expression of NF-κB/P65and BACE1protein in atorvastatin different dose group (8mg/kg and16mg/kg) decreased to different extent, among these groups, the high dosegroup (16mg/kg) decreased the most, compared with the model group, thedifference was statistically significant (P<0.05). Conclusions:Stimulated by inflammation and oxidative stress, theexpression of inflammation factor NF-κB protein increased in the ADrats.And as a transcription factor, NF-κB existed in BACE1promoter region,thus leading to the expression of BACE1protein increased..Atorvastatin candecrease the experimental AD model rats’ NF-κB and BACE1proteinexpression and improve their learning and memory ability. Data show that, thelearning and memory ability changes in AD rats created by atorvastatin wasprobably achieved by anti-inflammatory effect, which may be one of themechanisms of atorvastatin against AD.This experiment will provide newtheoretical basis and new ideas for the clinical treatment of AD.