Study On The Intervention Of Treadmill Exercise And Curcumin On NF-κB Signal Pathway In Alzheimer’s Disease Model

Research purposes: In our country,the number of elderly people is increasing over time,and senile diseases will also bring more and more serious problems to social and economic problems.Alzheimer’s disease(AD)is harmful to the elderly.Very large,as a neurodegenerative disease,it is chronic and irreversible.The earliest signs of AD are damage to recent memory function and the impact on language skills.AD gradually develops into severe dementia and coma.Bring a heavy burden to society and families.Nuclear factor kappa-B(NF-κB)is a cellular transcription factor.After NF-κB is activated,it will trigger a series of misregulations,which will lead to the occurrence of autoimmune diseases.At the same time,NF-κB also mediates a series of Pro-inflammatory cytokines.In neurons and astrocytes,the immune response of NF-κB appears abnormally active,which activates NF-κB and its associated signaling pathways,thereby making the pro-inflammatory cytokine tumor necrosis factor-α(tumor necrosis factor-α)active.-α,TNF-α),interleukin-1β(Interleukin-1β,IL-1β)and other expression levels increase accordingly.At present,clinical medicine has not been able to completely cure AD.The best method for AD is to prevent its occurrence and development.Exercise exercise can effectively improve the various functions of the brain has been proven by a large number of studies,promote the recovery of AD and other neurodegenerative diseases,exercise exercise has a prominent role in inhibiting the activation of NF-κB signaling pathways,and at the same time reduces glial cell It also has a significant effect on activation,thereby reducing the release of TNF-α,IL-1β and other related inflammatory factors in its signaling pathway,thereby preventing and alleviating the course of AD.At the same time,curcumin has anti-inflammatory and antioxidant effects and can play an important role in the treatment of AD.It can reduce neuronal apoptosis and reduce the production of inflammatory factors and oxygen free radicals by inhibiting the NF-κB signaling pathway.At present,the existing studies are mainly to treat AD through separate exercise intervention or separate drugs,and there are still few studies on the combination of exercise and drugs for AD.Therefore,this study established AD model rats by intraperitoneal injection of D-galactose combined with Al Cl3 gavage,and tried to use treadmill exercise and curcumin to intervene AD model rats through the NF-κB signaling pathway,and explore treadmill exercise and curcumin.The effect of combined intervention on the learning ability and memory ability of AD model rats,as well as the regulatory effect and molecular mechanism of NF-κB signaling pathway in AD.Hope to achieve better results and provide a scientific basis for the treatment of AD.Research method: In this study,60 male healthy SD rats were randomly divided into5 groups with 12 rats in each group.They are: normal control group(Normal Control Group,NC group),AD model group(Alzheimer Control Group,AC group),AD training group(Alzheimer Exercise Group,AE group),AD model control + curcumin group(Alzheimer Control+ Curcumin Group,AC+C group),AD model training +curcumin group(Alzheimer Exercise +Curcumin Group,AE+C group).The remaining four groups except the NC group were injected intraperitoneally with D-galactose [120mg/(kg·d)] and Al Cl3 [40mg/(kg·d)] in the morning every day for eight weeks.The NC group was injected with saline at the same dose as the other four groups.At the same time,every Monday to Friday morning,the AC+C group and AE+C group were given curcumin intragastric administration intervention for 8 weeks,the dose was 200mg/kg.d.The other three groups were given 0.5% sodium carboxymethylcellulose suspension by gavage,which was the same dose as curcumin.The AE group and AE+C group had eight weeks of treadmill training every afternoon.The training time is from Monday to Friday,and Saturday and Sunday are the rest periods.After the training,the Morris water maze experiment was carried out,mainly to evaluate the learning and memory ability and space exploration ability of the rats.After the water maze,the rats were fasted for 24 hours,then weighed,anesthetized,and then collected materials.7 animals in each group were directly decapitated and sacrificed after anesthesia.The hippocampus were taken out and stored in cold storage.The content of NF-κB protein was detected by Western-blot,IL-1β and TNF-a were detected by ELISA,and glutathione peroxidation was detected by enzyme labeling Hydrogenase(GSH-PX)content,superoxide dismutase(SOD)activity and malondialdehyde(MDA)content.The remaining 4-5 rats in each group were perfused after anesthesia,and the whole brain was taken out and placed in 4%paraformaldehyde for fixation for 24h～48h.After fixation,dehydration,transparency,embedding,and sectioning were performed,and HE staining and NIssl staining were performed to observe the changes in the neuron structure of the rat hippocampus.Research results:1)Through the results of the positioning and navigation experiment,it can be seen that the time for each group of rats to escape the incubation period gradually shortened as the experiment progressed.The NC group was the most obvious,followed by the AE+C group,and the other groups had varying degrees of shortening.The three-day shortening was obvious,and the fourth and fifth days were relatively stable.The results of the incubation period of the rats in each group of the five-day positioning navigation are generally NC group<AE+C group<AC+C group<AE group<AC group.2)The results of the space exploration experiment show that the results of the staying time in the quadrant of the virtual platform and the number of crossing the virtual platform of each group of rats are: NC group>AE+C group>AC+C group>AE group>AC group.3)Histological results,the results of HE staining and Nissl staining showed that the cells in the CA1 area of the hippocampus of the NC group were neatly arranged,the cell morphology and size were the same,the structure was complete and the density was higher;compared with the NC group,the AC group rats The cells in the hippocampal CA1 area are arranged chaotically,the intercellular spaces are enlarged and inconsistent in size,a large number of dead cells appear,and the nuclei are condensed and pyknotic;compared with the AC group,the AE group,AC+C group and AE+C group rat hippocampal CA1 area cells The overall arrangement is neat,the number of dead cells is reduced,the cell gap is reduced,and the cell morphology and structure are relatively complete.Among them,the number of dead cells in the hippocampal CA1 area of the AE+C group is the least,and the cell integrity is better.4)Western Blot experiment results showed that compared with the NC group,the expression of NF-κB protein in the AC group,the AE group and the AC+C group all increased significantly(P<0.01),and the AE+C group increased(P<0.05);Compared with the AC group,the AE group and AC+C histone expression decreased(P<0.05),and the AE+C group was significantly decreased(P<0.01);compared with the AE group,the AE+C histone expression decreased(P<0.05).5)The results of the ELISA experiment showed that the expression of IL-1β in the hippocampus of AD rats was increased compared with the NC group.The expression of IL-1β in the AC group,AE group,AC+C group and AE+C group increased(P<0.01);Compared with the AC group,IL-1β expression in the AE group,AC+C group and AE+C group was significantly reduced(P<0.01);compared with the AE group,the AC+C group decreased(P<0.05),AE+C decreased significantly(P<0.01);compared with AC+C group,AE+C group decreased(P<0.05).Compared with the NC group,the expression of TNF-α increased significantly in the AC group,AE group,AC+C group and AE+C group(P<0.01);compared with the AC group,the AE group decreased(P< 0.05),AC+C group,AE+C group decreased significantly(P<0.01);compared with AE group,AC+C group decreased(P>0.05),AE+C group decreased significantly(P< 0.01);Compared with AC+C,AE+C decreased(P>0.05).6)SOD,MDA,GSH-PX test results showed that in the hippocampus of each group of rats,the activity of SOD and GSH-PX was the highest in the NC group,followed by the AE+C group,followed by the AC+C and AE groups.The activity of the MDA group was the lowest.The activity of MDA was highest in the AC group,followed by the AE group and AC+C group,followed by the AE+C group,and the NC group had the lowest activity.Research conclusions: 1)After 8 weeks of treadmill exercise and curcumin intervention in AD model rats,their learning ability and memory ability were very effectively improved,and the effect of the combined intervention group of treadmill exercise and curcumin was the best.2)The 8-week treadmill exercise and curcumin intervention can effectively inhibit the activation of the NF-кB signaling pathway,reduce the inflammatory response in the brain of AD rats,and improve their learning and memory capabilities.Among them,the combined intervention of treadmill exercise and curcumin The effect is best.3)8 weeks of treadmill exercise and curcumin intervention can reduce the oxidative stress in the course of AD,and slow down the progression of AD disease.The combined intervention of treadmill exercise and curcumin has the best effect.