| Alzheimer’s disease(AD)is a neurodegenerative disease which has multiple pathogenesis and whose pathogenesis is not entirely clear.It is characterized by progressive cognitive decline,learning and memory capacity retrogression,daily activity disorders,neuropsychiatric symptoms and daily behavioral abnormalities.Neuroinflammatory response and neuronal apoptosis and Aβ formation and clearance imbalance induced by the extracellular amyloid beta protein(Aβ)abnormal deposition and intracellular tau hyperphosphorylation into neurofibrillary tangles(NFTs)are the main pathologic features.AD is the most common type of dementia all over the world.As the global population ages,the incidence is expected to increase rapidly,which will bring patients,families and society a heavy financial burden.Although the study of the pathogenesis of AD is getting deeper,AD is still refractory in the present and it can be difficult to stop the process of the disease,whereas research and development of effective AD drugs has become a huge challenge.Therefore,it would be of great social significance to explore a cost-effective drug to prevent and treatment AD on the basis of existing medications according to its pathogenesis,it will has a huge social significance and economic benefits.A large number of studies have substantiated that central inflammatory response plays a key role in the development and progression of AD.Neuroinflammatory reaction can induce the production of proinflammatory cytokines interleukin 1β(IL-1β)and tumor necrosis factor α(TNF-α).Anti-inflammatory factors IL-4,IL-10 and other deficiencies may also deteriorate the inflammatory response.The neurotoxicity of IL-1β and TNF-α can not only damage neurons and synapses,but also activate NF-κB.Furthermore,activated NF-κB can induce the expressions of IL-1β,TNF-α,i NOS and lipopolysaccharide factor,which formulated a malignant loop of chronic neuroinflammatory response.With the persistence of neuronal inflammatory response,unremitting lack of anti-inflammatory response to Pro-inflammatory stimulus,results in the imbalance of anti-inflammatory / proinflammatory cytoplasm,further intensifying the development of neuroinflammatory response.Therefore,the usage of it may be a potential new strategy for the prevention and treatment of AD to utilize anti-inflammatory drugs to inhibit neuroinflammation,protect neurons,and thus improve neuropathological changes.Aspirin is a classic non-steroidal anti-inflammatory drug(NSAIDs).A considerate number of clinical studies have suggested that the incidence of AD in people with long-term aspirin is lower than that of non-steroids.Therefore,this study established the AD animal model by injecting Aβ25-35 into the lateral ventricle of SD rats,and explored the anti-inflammatory effect of aspirin on the spatial learning ability and the expression level of anti-inflammatory cytokines IL-1β,TNF-α,IL-4 and IL-10 and nuclear transcription factor NF-κB,i NOS in the hippocampus of AD model rats,in order to provide empirical basis in the clinical trials and practical application of aspirin for AD prevention and treatment applications.Objective The central nervous system inflammatory response and anti-inflammatory/Objective The central nervous system inflammatory response and anti-inflammatory/ proinflammatory expression imbalance is thought to play a key role in the development and progression of AD.In this study,the AD model was established by injecting Aβ25-35 into the lateral ventricle of SD rats.After the intervention with aspirin,to study the effect of aspirin on the spatial learning and memory ability and the expression of inflammatory factors(IL-1β,TNF-α,IL-4 and IL-10)in hippocampus of AD model rats and the effect on the microbalance of anti-inflammatory/pro-inflammatory cytokines,and to further explore the potential preventive effect of aspirin on AD.Methods 40 male SD rats were divided into 4 experimental groups by completely randomized manner,n=10.(1)control group: free drinking distilled water,3 weeks after feeding,the use of brain stereotactic instrument in the right lateral ventricle of the rats injected 5μl of sterile saline,and then fed distilled water for 3 weeks;free to eat.(2)AD model group: After drinking for 3 weeks,5 μl Aβ25-35(10mmol/L)solution was injected into the right ventricle of the rat using the brain stereotactic instrument,and then fed with distilled water for 3 weeks.(3)low-dose of aspirin intervention group(1mg/ml): After drinking for 3 weeks,5μl of Aβ25-35(10mmol/L)solution was injected into the right ventricle of the brain using the brain stereotactic instrument,and then the rats were treated with distilled water for 3 weeks;free to eat.(4)high-dose aspirin intervention group(2mg/ml): free drinking distilled water,3 weeks after feeding,the use of brain stereotactic instrument in the right lateral ventricle injection of 5μl of Aβ25-35(10mmol/L)solution,Distilled water for 3 weeks;free to eat.The levels of IL-1β,TNF-α,IL-4 and IL-10 in hippocampus were detected by double antibody sandwich ELISA after Morris water maze was used to detect the spatial learning and memory ability of rats after 3 weeks of intracerebroventricular injection.The expression of NF-κB and i NOS was observed by immunohistochemical staining.Neuronal apoptosis was observed by Nissl’s staining.Results(1)Space learning and memory ability :Compared with the control group,the spatial learning and memory ability of AD model rats decreased significantly(P<0.001),1mg/ml Asp group compared with the control group,the difference was statistically significant(P<0.05),2mg/ml Asp group and control group,the difference was not statistically significant(P>0.05);Compared with AD model group,1mg/ml Asp group compared with model group,the difference was statistically significant(P<0.05),2mg/ml Asp group compared with mode group,the difference was statistically significant(P<0.01);low and high-dose Asp groups,the difference was not statistically significant(P>0.05).(2)The expression of IL-1β in hippocampus :Compared with the control group,the level increased significantly the expression of IL-1β in hippocampus tissue of rats in model group AD(P<0.001),group Asp intervention group and the control,there were no significant differences(P>0.05);compared with the AD model group,low dose and high dose intervention group the expression of IL-1β in Asp the average water decreased significantly,the differences were statistically significant(P<0.01);Asp intervention group was no statistically significant difference between groups(P>0.05).(3)The expression of TNF-α in hippocampus :compared with the control group,the hippocampal tissue of rats in the model group the expression of TNF-α was significantly increased(P<0.001),1mg/ml Asp group and control group,the difference was statistically significant(P<0.01);2mg/ml Asp group and control group,the difference was not statistically significant(P>0.05);the Asp intervention group compared with the AD model group,hippocampus Asp of rats in 2mg/ml group the expression of TNF-α significantly decreased(P<0.01),while the 1mg/ml Asp group compared with AD model group,the difference was not statistically significant(P>0.05);Asp intervention group was no statistically significant difference between groups(P>0.05).(4)The expression of IL-4 in hippocampus :compared with control group rats,IL-4 expression level decreased significantly in hippocampus tissue of rats in model group AD(P<0.001),1mg/ml Asp group and control group,the difference was statistically significant(P<0.01),2mg/ml Asp group and control group,the difference was not statistically significant(P>0.05);compared with the AD model group,significantly increased IL-4 expression in hippocampus tissue of rats in the Asp group 2mg/ml,the difference was statistically significant(P<0.01),1mg/ml Asp group compared with AD group,the difference was not statistically significant(P>0.05);Asp intervention group,the difference was not statistically significant(P>0.05).(5)The expression of IL-10 in hippocampus:Compared with the control group,the level of expression of IL-10 decreased significantly in hippocampus tissue of rats in model group AD(P<0.01),1mg/ml Asp group and control group,the difference was not statistically significant(P>0.05),2mg/ml Asp group and control group,the difference was not statistically significant(P>0.05);compared with the model group,the hippocampal tissue of rats in the Asp group the 2mg/ml IL-10 expression level was significantly higher(P<0.05),1mg/ml rats in the Asp group compared with AD group,the difference was not statistically significant(P>0.05);Asp intervention group,the difference was not statistically significant(P>0.05).(6)The positive expression of NF-κB and i NOS in hippocampus:Compared with the control group,NF-κB and the positive expression of i NOS in hippocampus in AD model group was significantly increased,neuronal loss is obvious and the Asp in the intervention group had different levels in the hippocampus of NF-κB,i NOS expression and neuronal loss,2mg/ml Asp intervention group and the control group is roughly equal.(7)The neurons of hippocampus:Compared with the control group,the neurons in the hippocampus were significantly absent in the AD model group,and the neurons were varying degrees absent in the hippocampus of the Asp intervention groups.The neurons in the 2mg/ml Asp intervention group were not significantly different from those in the control group.Conclusions Aspirin could improve the spatial learning and memory ability of AD model rats.Aspirin could inhibit the expression of NF-κB pathway and i NOS,adjustment the expression of the pro-inflammatory factors IL-1β,TNF-α and the expression of the anti-inflammatory factors IL-4,IL-10,thus promote pro-inflammatory/anti-inflammatory factors tend to rebalance in the pathogenesis of AD inhibition of the development of inflammatory response,play anti-inflammatory and protective neurons.. |
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