The Effect Of Highly Synergistic Nano-drug Delivery System On The Cognitive Function Of APP/PS1 Transgenic Mice

Objective:To observe the effect of highly synergistic nano-drug delivery system on the cognitive function of APP/PS1 transgenic mice.Method:One hundred APP/PS1 transgenic mice(male,6 months old)were randomly divided into 6 groups: AD model group(routine feeding without any intervention),chloroiodoquinolone(zinc ion chelator)nanoparticles group,donepezil(cholinesterase inhibitor)nanoparticles group,empty nanoparticles group,joint drug-loaded nanoparticles group,and normal saline group.Chloroiodoquinolone and donepezil were intranasally administered solely and jointly by the highly synergistic nano-drug delivery system once per day for concecutive 30 days.All groups were performed Morris water maze behavior test,HE staining,immunohistochemistry,EEG power spectrum,and the ultrastructural observation of hippocampus pre and pro the delivery duration.Results: 1.The Mirros water maze: positioning navigation experimen after drug deliveryt: intra-group comparison: the mean escape latency of the first 3days after the administration of combined granules,donepezil granules,and the mean escape latency of the whole training time were lower than that before the administration,and the difference was statistically significant(P<0.01).Comparison between groups after administration: the difference of the mean evading incubation period before and after administration,the combined drug delivery granule group had the highest value.Space exploration experiment: intra-group comparison: the swimming time in the target quadrant/total time after administration was higher in the donepezil granule group,the empty granule group and combined administration granule group than brfore,and the differernce between the combined administration granule and the donepezil granule group was ststistically significant(P<0.05).2.HE staining: after the administration of high synergistic nano-drug delivery system,the hippocampal CA1 region of the mice in the three groups of chloroiodoquinolone nanoparticles group,donepezil nanoparticles group,joint drug-loaded nanoparticles group was more closely arranged and the number of cellswas increased than that before the administration.3.Immunohistochemistry: expression level of Ach : the Ach expression level in the combined drug group was higher than that in the empty pellet group and APP/PS1group(1 month ago),and the difference was statistically significant(P<0.01).The Ach expression was the highest in the donepezil granules group,and the difference between it and other groups was statistically significant(P<0.05).Expression level of A?: the expression level of A? in the combined group was lower than that in the normal saline group,AD model group and empty granule group,and the difference was not statistically significant(P>0.05).4.Electroencephalogram power spectrum of cognitive cerebral cortex: frontal area:the donepezil granule group was higher than the normal saline group,APP/PS1(1month ago)group and the combined administration group,and the differences were statistically significant(P<0.05).temporal region: ? band: the combined administration group was higher than the normal saline group and the empty particles group,showing a statistical difference(P<0.05).? band: the combined drug delivery granules were lower than those in the normal saline group,donepezil granules group,chloroiodohydroquinolate granules group,empty granules group and AD model group,with statistically significant differences(P<0.05)5.Observation of hippocampal ultrastructure: The synapses in the combined granule group were of obvious semilunar type,and the morphology of mitochondria,endoplasmic reticulum and ribosome was more regular than that in the other groups,and the attachment of postsynaptic membrane densities was obvious.Most of the synapses in the rest groups were mixed with half-moon type and flat type,and the synapses in AD model group,empty particle group and normal saline group were mainly flat type.The number of synapses in the combination granule group,donepezil granule group,and chloroiodohydroxyquine granule group were all increased compared with APP/PS1(1 month ago)after administration.