Study Of Bs-5-YHEDA Iron Chelating Peptide Combined With Semaglutide In The Treatment Of AD Model Mice

Objective: To investigate the effect of bs-5-YHEDA iron chelating peptide combined with Semaglutide on the cognitive ability and pathological characteristics of Gal-D-induced Alzheimer’s disease(AD)model mice.Method: Fifty-six mice were randomly divided into seven groups,namely blank group,model group,bs-5-YHEDA iron chelating peptide group,Semaglutide group,Desferal group,combined treatment group,and Memantine group,with 8 mice in each group,half of each sex.Except for the blank group,the AD mouse model was induced by intraperitoneal injection of D-galactose for 6 consecutive weeks.Each treatment group was given the corresponding drug continuously for 3 consecutive weeks starting from the 4th week,and the blank group and the model group were injected with the same dose of saline.At the end of the treatment cycle,the learning and memory abilities of mice were examined by Morris water maze behavioral assay.Blood samples and brain tissue samples were obtained by autopsy.Brain tissue sections were stained with hematoxylin-eosin(HE)and microscopically observed for pathological changes in the hippocampal region.Aβ expression and Tau protein phosphorylation levels,as well as inflammatory factor content,were further examined by immunohistochemistry,enzyme-linked immunosorbent assay(ELISA),and immunoblot(Western Blot)tests.Result: In the Morris water maze space exploration experiment,the differences in the number of times the mice traversed the platform,the ratio of swimming distance to the target quadrant and the time ratio were statistically significant in each group(P<0.05);compared with the model group,the number of mice crossing the platform significantly increased in the Semaglutide group,and the differences were statistically significant(P<0.001);In contrast,there was no significant increase in the number of platform crossings in both the bs-5-YHEDA iron chelating peptide group and the combination treatment group compared to the PBS administration group.The results of HE staining showed that the hippocampal cone cells in the model group had reduced levels,disorganized arrangement,cell edema and deep staining of nucleus fixation compared with the mice in the blank group.The disorganized cell arrangement,deep staining of nuclei and apoptosis in the hippocampal area of each treatment group were significantly improved after drug treatment.The results of immunohistochemistry and WB showed that the Aβ expression level and Tau protein phosphorylation level of mice in the model group were significantly increased compared with those in the blank group,and the Aβ expression level and Tau protein phosphorylation level of mice in each group were significantly decreased after drug treatment,and the differences were statistically significant(P<0.05).Conclusion: The combination of bs-5-YHEDA iron chelating peptide with Semaglutide can effectively improve the learning and memory ability and pathological characteristics of AD mice,but the treatment effect was not significantly improved in the combination treatment group compared to single bs-5-YHEDA iron chelating peptide or single Semaglutide treatment,which suggests that there may be a threshold effect of our dual-target combination therapy,after which superimposed drug interventions no longer improve disease progression.Therefore,the construction of AD model mice and the duration of treatment need to be further optimized and explored.