| The clinical study shows that Kaixin Jieyu Prescription(KXJYP)can effectively improve the symptom of vascular depression including depressed mood,loss of interest,the effect is better than citalopram and fluoxetine in improving the accompanying physical symptoms especially on chest tightness,sigh,fatigue,insomnia,poor appetite,reflecting KXJYP’ advantage in treatment of vascular depression.In the application,it is found that KXJYP is not only effective for elderly patients with vascular depression,but also has good effects on depression,anxiety,fatigue in young and middle-aged.In order to give full play to KXJYP’value,based on the previous animal experimental in vascular depression model,we further explored the antidepressant effect of KXJYP on the hippocampal structure and adult hippocampus neurogenesis of rats with depression model.In order to make full use of traditional Chinese medicine’ advantages of low side effects and easily accepted by the patients,and develop the application value of effective prescriptions and meet the multifaceted clinical needs of depressive patients,based on the animal model experiment of early vascular depression,this experiment further studied the antidepressant effect and antidepressant mechanism of KXJYP on depressed animal models.ObjectivesBehavioral experiments were carried out on rats with depression,to evaluate the direct effect of KXJYP on the antidepressant.The ultrastructure,pathomorphology and identification of nerve regeneration markers were observed,to explore the protective effect of KXJYP on neurons in hippocampus of key areas in depression and its effect on adult nerve regeneration,furthermore,the effects on brain structure and function plasticity were preliminarily discussed.In order to expand the adaptation of KXJYP,and promote the two development,furthermore,meet the drug needs of patients with depression more efficiently,and further provide basic experimental support.Methods1 Based on the Sucrose preference test(SPT),the rats were divided into normal control group and model group,the chronic unpredictable mild stress interference in healthy adult male rats for 4 weeks,imitating the state of the anhedonia of depression.According to the SPT,again,the model group were randomly divided into model group,fluoxetine group,KXJYP group.The drug groups were given 4 weeks of continuous administration,The model group and normal group were given equal volume of pure water.The SPT were recorded every week in each group,and the forced swimming test was carried out 2 weeks and 4 weeks after administration.2 After 4 weeks of treatment in all groups,the hippocampal DG subarea’ultrastructure was observed by electron microscope,and the whole brain tissue was taken,fixed,embedded,cutted into slices,then the slices were stained with hematoxylin-eosin staining.Under the microscope,the hippocampal CA1,CA2,CA31,CA4,DG’cell levels,cell number,cell arrangement distribution and cell morphology were photographed and were analyzed by descriptive study.3 After 4 weeks of treatment in all groups,take the whole brain and make frozen sections for immunofluorescence staining of DCX.The number of DCX+ cells in SGZ were counted under a fluorescence microscope.Results1Through SPT analysis:compared with the normal group,the sucrose preference of the model group showed a continuous decline,to reach the lowest level in the 5 weeks.Compared with the model group,the sucrose preference in the KXJYP group increased in the first week,up to 3 weeks of drug delivery.Compared with the model group,the sucrose preference in the fluoxetine group increased after 2 weeks of administration,up to 4 weeks of drug delivery.After four weeks of administration,there was no difference in SPT between groups(P>0.05).The immobility time in forced swimming test:after 2 and 4 weeks of administration,compared with the normal group,the model group notably increased the immobility time.Compared with the model group,KXJYP group and fluoxetine group respectively shortened the immobility time,and KXJYP group,the immobility time significantly reduced(P<0.01)in the 2 week and 4 weeks of administration,fluoxetine group’ immobility time significantly reduced(P<0.01)in the 4 weeks of administration.2 Under light microscope,the morphology of neurons in each subarea of hippocampus was analyzed.Compared with normal group,the morphology of the model group’neurons in CA2,CA3 and DG regions showed significant abnormalities.There were no abnormality in CA1 and CA4 regions.In the normal group,the cells in CA2 and CA3 regions were clear,arranged closely and orderly,and the cell structure was clear.In CA2 region,in the model group,the cell level became smaller,the number of cells decreased significantly,the cell gap increased,the arrangement was chaotic and loose,and the cell structure was fuzzy,the fluoxetine group and the KXJYP group were close to the normal group.In CA3 region,in the model group,the number of cells decreased significantly,the cell gap increased,the arrangement was loose,the fluoxetine group and the KXJYP group were close to the normal group,but in KXJYP group some of the cells were lost.In DG region,from the cell level and number,the DG cell layer of the normal group was thick and closely arranged,in the model group,the cell layer became thinner,the number of cells decreased significantly,and the cell gap increased,the fluoxetine group was close to the normal group,and the cell arrangement of the KXJYP group was slightly loose than that of the normal group.In terms of cell morphology,compared with the normal group,the cell structure of each group was clear,but there were different degrees of neuronal cell edema in each drug group,,and the edema cells in fluoxetine group were the most.Under electron microscope,after 4 weeks of administration,granule cell ’structure in normal group was clear,nuclear membrane was smooth,evenly distributed chromatin.In model group,the cell contour disappeared,the mitochondrias was swelling,the mitochondrial crista decreased,or even disappeared,nuclear fragmentation.The cell contour of the fluoxetine group was still in existence,but the cell structure was dense,the cell membrane was dissolved,the cytoplasm was condense,the mitochondria was swollen and their crista fragmented,the nuclear membrane was wavy,the nucleus shrinked,losting the original form.In the KXJYP’ group,the cell profile was clear,the cell structure was not abnormal,the mitochondrias was swelling,the mitochondrial crista decreased,or even disappeared,the nuclear membrane was smooth,and the chromatin was evenly distributed.3 The immunofluorescence staining results of DCX showed that there was no significant difference in the number of DCX+ cells in each group(P>0.05).It can be seen from the standard deviation that the number of SGZ DCX+ in each group is quite different,although there was no statistical significance in each group,the trend that the number of DCX+ cells in model group decreased,in fluoxetine group and KXJYP group increased was present.ConclusionsKaixin Jieyu Prescription has a good antidepressant effect in the depression model rats,and the onset time may be earlier than fluoxetine.The antidepressant effect of KXJYP may be related to the protection of hippocampal neurons,the promotion of nerve regeneration and remodeling of hippocampal structure and function.Hippocampal SGZ nerve regeneration in depression model rats may be influenced by individual differences of experimental animals. |
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