Dabuyuan Jian Combined With Exercise Improves Learning Memory In AD Rats By Modulating PI3K/AKT/GSK-3β Signaling Pathway

Objective:Alzheimer’s disease（AD）is a progressive central neurodegenerative disorder that occurs mainly in old age and pre-aging,specifically manifested by cognitive dysfunction and behavioral impairment.In this paper,we investigated the effects of 4-week aerobic exercise combined with Tai Teng Yuan Decoction on regulating the expression of apoptosis-related proteins and key proteins in the signaling pathway PI3K/AKT/GSK-3βin AD rats from the perspectives of Chinese medicine theory and exercise physiology and explored the possible mechanisms of the effects of aerobic exercise combined with Tai Teng Yuan Decoction on improving cognitive dysfunction in AD rats from a comprehensive theoretical and experimental study.Methods.1.Theoretical exploration:We reviewed and combed the relevant literature,summarized the knowledge of exercise and AD in ancient medical and exercise physiology,explored the effect of aerobic exercise on cognitive dysfunction,and provided a theoretical basis for the improvement of cognitive dysfunction in AD by combining exercise with Davidian Yuan Decoction.2.experimental study:50 SPF class male SD rats were randomly divided into sham operation group（sham group）,animal model group（AD group）,aerobic exercise group（EX group）,Tai Tonic Yuan Decoction group（TCM group）,aerobic exercise+Tai Tonic Yuan Decoction group（EX+TCM group）using the random number table method,10 rats in each group.the AD group,EX group,TCM group,and EX+TCM group were established for AD The rats were injected with Aβ_25-35in the hippocampus of SD rats,and the rats in the sham group were injected with the same amount of saline instead of Aβ_25-35,and the operation method was the same.4 weeks of aerobic exercise were performed in the EX group and EX+TCM group,and 4 weeks of gavage with the Great Tonic Decoction were given in the TCM and EX+TCM groups.The morphological changes of hippocampal histology were observed by HE staining（hematoxylin-eosin staining）,the ultrastructural morphology of neurons was observed by transmission electron microscopy,and AKT,p AKT,GSK-3β,p GSK-3β,β-catenin,Bcl-2,BAX,Caspase3 proteins were detected in hippocampal tissues by Western Blot（immunoblotting test）.expression levels and the Morris water maze assay was used to detect the spatial memory ability of rats.Results.1.Modeling results:In general state,rats in the sham group were emotionally stable,with neat and shiny fur,active spirit,and normal activities;rats in the AD group were emotionally irritable and in a depressed state,with dry and disorganized fur and uninspired spirit relative to rats in the sham group.Weighing of the rats in each group before modeling showed that there was no significant difference in the bodyweight of the rats in each group,and the comparison of the bodyweight growth rate of the rats after modeling showed that the AD group,EX group,TCM group,and EX+TCM group were significantly lower than the sham group.2.HE staining results showed that the hippocampal cone cells in the AD group were loosely arranged and disorganized with lower density compared with the sham group;compared with the AD group,the cone cells in the EX group,TCM group,and EX+TCM group was regularly arranged and the number of cells increased.The results of transmission electron microscopy showed that the ultrastructure of the hippocampus in the AD group showed myelin-like changes and blurred mitochondrial swelling compared with the sham group;compared with the AD group,EX group,TCM group,and EX+TCM group,the myelin-like changes were reduced and mitochondrial swelling was improved under an electron microscope.4.WB results showed that the levels of Bcl-2,p AKT,and p GSK-3βwere significantly decreased,β-catenin expression was decreased（P<0.01）,and Caspase3 expression was upregulated（P<0.01）in the AD group compared with the sham group;Bcl-2,p AKT and p GSK-3βexpression were increased in the EX,TCM and EX+TCM groups compared with the AD group,and Caspase3expression was increased in the EX,TCM and EX+TCM groups.The expression of Bcl-2,p AKT,and pgs was increased in EX,TCM and EX+TCM groups,and the expression of caspase3 was down-regulated,and the level ofβ-catenin was increased in EX+TCM group,while there was no statistical significance in EX and TCM groups compared with AD group.The results of Morris water maze showed that the latency of evasion was significantly longer and the total swimming distance was significantly increased in the AD group compared with the sham group,and the residence time in the target quadrant was significantly reduced in the spatial exploration experiment（P<0.05）;compared with the AD group,the latency and swimming distance were significantly reduced in the EX,TCM and EX+TCM groups,and the residence time in the target quadrant was increased..Conclusions.1.In this study,the AD rat model was established by Aβlateral ventricular injection,and the behavioral changes,pathological alterations and ultrastructural differences were observed in each group of rats.The above results indicated that the neurons in the hippocampal region of AD rats were damaged,indicating that the hippocampus of the AD group rats basically mimicked the pathological state of AD,and the establishment of the animal model was better accomplished in this experiment.2.It can be further speculated by the pathomorphological results that the protective effect of exercise combined with Chinese medicine on hippocampal neurons is more obvious.It was observed under electron microscope that the comparison of rats with three intervention modalities,aerobic exercise combined with Tai Teng Yuan Decoction was chosen as more appropriate in alleviating synaptic damage in AD brain.3.In conclusion,exercise training combined with Tai Teng Yuan Decoction can improve learning memory function and alleviate hippocampal neuronal damage in AD rats,and the mechanism may be related to the regulation of PI3K/AKT/GSK-3βsignaling pathway and downstream proteinβ-catenin expression,and the combinate,ion of the two is superior to exercise intervention or pharmacological intervention alone.