Research On The Mechanism Of Eeffects Of Alcoholextract Of Euonymus Alatus On Learning And Memoryin Rats With AD Model Based On The NF-?B Signalingpathway

ObjectivesResearch on the Mechanism of Eeffects of Alcohol extract of Euonymus Alatus on Learning and Memory in Rats with AD Model Based on the NF-?B Signaling Pathway.To provide experimental basis for the prevention and treatment of AD by alcohol extract of Euonymus Alatus.Methods60 Rats was divided into 6 groups,them were respectively sham operation group?SG?,model group?MG?,donepezil Hydrochloride group?DPH?,low,medium and high dose groups of Euonymus alatus's alcohol extract?EA-L,EA-M,EA-H?,the treatment group and MG were given A?_25-355-35 bilateral hippocampal injection replication AD model,and the sham operation group was injected with an equal volume of sterile physiological saline.The rats in the sham operation group and the model group were given double distilled water,the western medicine group were given donepezil hydrochloride tablets,the the alcohol extract of Euonymus alatus group were given different doses of alcohol extracts of Euonymus alatus for 4 weeks.After four weeks treatment,the learning and memory ability were tested by Morris water maze test in Rats.Wst-1 method was used to detect the activity of SOD and the content of MDA in the hippocampal tissue of rats.And the effect of the alcohol extract of Euonymus alatus on oxidative stress in AD model rats was observed.The levels of serum 1L-1?and TNF-?inflammatory factors were detected by ELISA.HE and Nissl staining methods were used to observe the histomorphological changes in the hippocampal CA1 area of rats.Western Blot analysis of NF-?B,I?B-?,caspase-3expression.Results1.Morris water maze experiment?positioning navigation and space exploration experiment?:The positioning navigation experiment showed that compared with SG,the migrating latency of MG rats decreased slowly;each treatment group was significantly better than the model group.The space exploration experiment showed that the number of crossings of the MG rats was reduced,the time of passing the original platform for the first time was increased,and the time of swimming in the target quadrant was shortened.Compared with MG,the learning and memory ability of the rats in each treatment group was significantly improved.2.Oxidative stress index in rat hippocampus:Compared with SG,the activity of SOD in brain tissue of MG rats was significantly decreased,and the content of MDA was significantly increased?P<0.01?.Compared with MG,SOD in brain tissue of rats in each treatment group The activity was significantly increased,and the MDA content in brain tissue of EA-M,EA-H and DPH rats was significantly decreased?P<0.05 or P<0.01?.There was a significant dose dependence.3.The content of inflammatory factors in serum of rats:Compared with SG,the levels of inflammatory factors IL-1?and TNF-?in MG rats were significantly increased?P<0.01?.Compared with MG,EA-M,EA-H and DPH were larger.The levels of TNF-?and IL-1?in serum were significantly decreased?P<0.05?,and EA-H and DPH were significantly?P<0.01?.There was a significant dose dependence.4.HE,Nissl staining results:HE:model group,the hippocampus area of rats is abnormal,the number of neurons is significantly reduced,the number of pyramidal cells is reduced,the cells are disordered,thinned,scattered and even interrupted.At the same time,many cells were reduced in size,nucleus pyknosis,deepening staining,and a large number of small glial cells proliferated;in the treatment group,the number of neuronal cells increased,the cells were arranged neatly,the distribution was relatively uniform,and the intracellular structure was clear and normal.Cell proliferation is reduced.Nissl:The positive staining cells in the hippocampus of the model group were significantly decreased,and the cells were loosely arranged.The positive staining cells in the hippocampus of the treatment group were significantly increased,and the cells were arranged relatively closely.5.Western blot results:Compared with SG,the expression of NF-?B and caspase-3 in MG rats was significantly increased?P<0.01?;the expression of I?B-?was significantly decreased?P<0.01?.Compared with MG,the expression of NF-?B?caspase-3protein in EM-M,EA-H and DPH was significantly decreased.?P<0.05 or P<0.01?;the expression of I?B-?in EM-M,EA-H and DPH was significantly increased?P<0.05 or P<0.01?.There was a significant dose dependence.Conclusion1.The alcohol extract of Euonymus alatus can improve the learning and memory ability of AD model rats.2.The mechanism of the alcohol extract of Euonymus alatus to improve the learning and memory ability of AD model rats may be related to its anti-inflammatory and anti-oxidation effects:?1?By increasing the activity of SOD and reducing MDA content in hippocampus;?2?reduce the levels of inflammatory cytokines 1L-1?and TNF-?,inhibit IkB-?,promote the expression of NF-?B and Caspase-3.Through anti-inflammatory and anti-oxidative can inhibit and eliminate the production of A?,the rats'learning and memory ability has increased,and the role of prevention and treatment of AD has exerted.