Based On The "neuro-endocrine-immune" Regulation Mechanism, The Effect Of Compound Chaijin Jieyu Tablet On The Synaptic Damage Of Hippocampal Neurons In Depression Model Rats Was Studied

OBJECTIVE:The chronic stress depression model rats and depression model fetal rat hippocampal neurons as the research object,from the behavior,blood biochemistry,histopathology,electrophysiology and molecular biology of cells,and from the perspective of"nerve-endocrine-immune"to investigate the role of the treatment of Compound Chaijin Jieyu Tablet?CJJY?on depression.To study its mechanism of nerve protective effect.To provide theoretical basis for contemporary antidepressants work of traditional Chinese medicine and experimental basis.METHODS:1.In vivo:112 male SD rats were randomly divided into 7 groups based on the partial addicted to sugar water degrees:the blank control group,chronic stress group,CJJY 4 times(2.7 g·kg^-1),2 times(1.35 g·kg^-1),1 times(0.675 g·kg^-1),0.5(0.3375 g·kg^-1)dose group and Venlafaxine group(13.5 mg·kg^-1).Chronic unpredictable stress was used to establish a depression model for28 consecutive days.The changes of partial preference of sugar water were detected weekly.Morris water maze,open-field experiment,novelty-suppressed feeding experiment and forced swimming test were used to evaluate the changes of rats'behavior.Plasma levels of CRH,ACTH,CORT and serum levels of TGF-?,TNF-?,IL-8,IL-10,IL-18 were determined by ELISA.Golgi-cox staining was used to observe the morphological changes of dendritic spines,dendritic branches and cell bodies of neurons in the CA1 and DG regions of the hippocampus.2.In vitro:the cultured hippocampal neurons were randomly divided into 5 groups:blank control group,depression model group,blank serum group,CJJY group,and Venlafaxine group.The corresponding reagents were added to the medium 18h before the test according to the groups:the blank control group was given the same amount of culture medium,the rest groups were added with CORT?50 M?for depression modeling,and the corresponding volume fraction of10%blank serum and drug-containing serum were added for intervention.High content cell imaging was used to detect the concentration of intracellular Ca²⁺and the expression changesof NR2A,NR2B,SynGAP,SYN-?,PSD-95 and CaMK?;Whole-cell patch clamp was used to record the mEPSC of neurons,and the differences in frequency and current amplitude of each group were compared.RESULTS:1.Compared with blank control group,chronic stress group rats partial preference of sugar water decreased obviously?P<0.05?,learning and memory ability decreased?P<0.05?,the number of independent inquiry activity significantly reduced?P<0.01?,the incubation period increased?P<0.05?,the immobility time of swimming significantly prolonged?P<0.01?,the level of CRH,ACTH and CORT in plasma increased?P<0.05 or P<0.01?,the level of TGF-?and IL-10 in serum significantly decreased?P<0.05 or P<0.01?,the level of TNF-?,IL-8 and IL-18 were significantly increased?P<0.05 or P<0.01?,some neurons disappeared in the hippocampus CA1and DG regions,the dendritic distribution was disorderly and loose,and the number of dendritic spines was significantly reduced or absent.Compared with the chronic stress group,the changes of the above indexes could be reversed to a certain extent in each dose group of CJJY and venlafaxine group?P<0.05 or P<0.01?.2.Compared with the blank control group,the average fluorescence intensity of intracellular Ca²⁺and NR2A,NR2B,SYN-alpha,PSD-95 significantly increased?P<0.05 or P<0.01?in the depression model group and blank serum group,the fluorescence intensity of SynGAP and CaMK?decreased?P<0.05?,the mEPSC amplitude and frequency were significantly increased?P<0.05?;Compared with the blank serum group,the changes of the above indicators in both the CJJY group and Venlafaxine group could be reversed to some extent?P<0.05 or P<0.01?.CONCLUSION:1.CJJY can improve anhedonia and lack of interest in chronic stress depression model rats,improve learning and memory ability,and alleviate depression-like behavior;2.CJJY can significantly improve the HPA axis disorder in chronic stress depression model rats,and maintain the homeostasis of the internal environment;3.CJJY can reverse the abnormal proportion of anti-inflammatory and proinflammatory cytokines in rats with chronic stress depression,improve inflammatory response and regulate neuro-immune function;4.CJJY can improve the synaptic function and structural damage of hippocampal neurons in depressed rats,and has an obvious protective effect on neurons;5.The anti-depression effect of CJJY may be the overall regulation of"neuro-endocrine-immune".