Apigenin Plays A Positive Role In Reducing The Expression Of HMGB1/RAGE/NF-κB Passway In The Rat Model Of Alzheimer’s Disease

Objectives:As the development of times and scientific progress,people’s material culture has been enhanced.We pay attention not only to the material pursuing but also to spiritual enjoyment.However,Alzheimer’s disease effects the quality of significantly.Congnitive disorder is one clinical symptom of Alzheimer’s disease,which influences people’s later life the most.There are 356000000 patients with Alzheimer’s disease all around the world in 2012 and 7700000 cases will increase per year.Alzheimerls disease is a hard treated neurodegenerative disease.The morbidity of Alzheimer’s disease rise with age.Forgetfulness,congnitive disorder,mental emotional disorder and behavior disorder are clinical symptoms and the pathological features of Alzheimwer’s disease are plaques,neurofibrillary tangles（NFTs）,hippocampal pyramidal cell particles vacuoles degeneration,extensive loss of neuronal.β-amyloid（Aβ）plaques accumulation,tau protein hyperphosphorylation,nerve vascular dysfunction,abnormal cell cycle,inflammation,oxidative stess and mitochondrial disorder may be the pathogenesis of Alzheimer’s disease.It has been discovered that inflammation is the commom point of all known pathogenesis and nervous lesion in the brain,NFTs can lead to neuroinflammation.The inflammation of Alzheimer’s disease can be caused by the nervoud lesion which generated by the inflammatory mediator released by activated neurogliocyte aroung Aβ.High Mobility Group-B1（HMGB1）is a inflammatory mediator which can be relseased by the microgliacyte,astrocyte and neuron.HMGB1 is able to bring about inflammatory reaction to cause cells death.HMGB1 is closely related to the toxicity and metabolism of Aβ,moreover,the inflammatory response which resulted from Aβ can add the expression of HMGB1.Nuclear factor-κB（NF-κB）will trans from cytoplasm to karyon to bring about inflamatory reaction,if HMGB1 is combined with Receptor For Advanced Glycation Endproducts（RAGE）.Thus it can be seen that we can try to cut down the the expression of HMGB1/RAGE/ NF-κB passway to lighten the inflammatory reaction and slow the process of Alzheimer’s disease.Apigenin（Api）is a kind of flavonoid that can be extracted from fruits,vegetables and other variety of plants.It is avirulent and no mutated.Study showed that Apigenin is able to inhibit inflammatory reaction,moreover,it can light inflammatory reaction through restrain NF-κB nuclear translocation.More and more reseaches are on curing Alzheimer’s disease with Apigenin,but there is a few of Apigenin action on HMGB1/RAGE/ NF-κB passway.Methods:48 aged 10-12 weeks clean grade healthy male SD rats were prepared（none of them was congenital dementia or with other unsuitable factors）.SD rats were assigned randomly into four groups: Sham group,Sham +Api group,AD group and AD+ Api group.Sham +Api group and AD+ Api group were intraperitoneal injected（ip）with Apigenin 20mg/kg/day.At the same time,Sham group and AD group were intraperitoneal injected with isometric solvent everyday.With the help of stereotaxic apparatus,Dissolved Aβ_1-42 were injected into the hippocampus of AD group,AD+ Api group and isometric solvent were injected into the hippocampus of Sham group,Sham +Api group.Then,test the behavior of SD rats with Morris water maze.The differences of pathologic chances of each group were observed by hematoxylin-eosin（HE）pigmentation.The expressions of GFAP、Iba-1、HMGB1、RAGE and NF-κB p65 were measured with immunohistochemical and Western-blot detection.Results:1 Morris water maze:The learning and memory ability of AD group was worse then other three groups.2 HE pigmentation:The pathologic chances of each group were not the same.The cellular forms and structures of Sham group had no obvious change.Sham group and Sham +Api group were similar.The CA1 region cells of AD group hippocampus were lost of normal form,heavy staining and not well aligned.Abnormal cells of AD+Api group were fewer than AD group.3 Immunohistochemical Result: The expressions of GFAP and Iba-1 of AD group increased obviously（P<0.05）and decreased after Apigenin injection.HMGB1 mainly expressed in cytoplasm in AD group and other groups expressed in karyon.RAGE expressed more in AD group than others.NF-κB p65 mainly expressed in karyon in AD group and other groups expressed in the cytoplasm.4 Western-blot detection Result:The expressions of GFAP、Iba-1、HMGB1 and RAGE were higher than other groups（P<0.05）.NF-κB p65 of AD group expressed the most in karyon of these four groups and the least in cytoplasm.Conclusions:1 The model of Alzheimer’s disease is succeed after Aβ_1-42 injecting into bilateral hippocampus.AD group rats appears congnitive disorder and behavior disorder.Pathologic chances of Alzheimer’s disease can be seen in hippocampus.2 The injection of Aβ_1-42 activates microgliacyte and astrocyte.The expression levels of GFAP、Iba-1、HMGB1、RAGE、NF-κB p65 fully prove that Aβ_1-42 can arouse inflammatory response and this inflammatory response plays an important role in Alzheimer’s disease.3 Apigenin can decline the congnitive disorder,behavior disorder and GFAP、Iba-1、HMGB1、RAGE、NF-κB p65 which are caused by Aβ_1-42.This research reveals that Apigenin is able to protect nerves and down regulate the inflammatory reaction.