| Objective:Depression is one of the most common mental disease and one of the reason that result in major psychosocial disorders and social dysfunction.Although there are many psychotropic drugs to choose,the drugs has no effect on about 40 percent of patients with depression.The reason lies in lack of knowledge about the depression at the onset of illness,inapprehension of pathophysiological mechanisms of depression and most clinical drugs currently used are biosynthetic.Promoting regeneration of hippocampal nerve play an important role in the mechanism of antidepressant therapy.MieroRNA has received high attention in the regulatory mechanism of neurologic disease due to its decisive role in the regeneration of nerve.miR-124 which is abundant in the brain is the important regulator of the process of neurogenesis.According to the theory of traditional Chinese medicine,the liver is mainly used to relieve and regulate the emotion,the liver-regulating compound recipe has been widely used in the treatment of the emotional illness.JWSNS compound recipe is based on the theory of zang-manifestations,and has been used in the comprehensive treatment of the liver dysfunction.JWSNS have the whole regulation function,which shows the prospect of development.In this study,we further study the anti-depression mechanism of liver-regulating compound recipe in the view of the relationship between miR-124 and neurogenesis to provide a new idea for prevention of emotional illness which caused by liver dysfunction,moreover to lay the foundation for the development of new traditional Chinese drugs those apply to anti-chronic psychological stress as well.Methods:Step one.Prepare the unpredictable chronic stress rat model,detect the changes of relate index by using the means of real-time fluorescence quantitative per,immunofluorescence and hybridization in situ.Observe the depression changes of the unpredictable chronic stress rat model,the changes of miR-124 content in hippocampus DG region,and the proliferation and differentiation of neural stem cells in hippocampus DG region as well.The relationship between miR-124 and neurogenesis in the DG region was observed in parallel;Step two.Culture the hippocampal neural stem cells.The miR-124 functional gain model and the miR-124 functional loss model were prepared,and the relationship between miR-124 and neurogenesis of hippocampal neural stem cells was further study by using cellular immunofluorescence double labeling;Step three.Use liver-regulating compound recipe JWSNS to intervene the miR-124 functional gain model and the miR-124 functional loss model,to observe the effect of liver-regulating compound recipe on neural stem cell miR-124 and the proliferation of neural stem cells.Results:Part one.Different behavior happen at different times in the process of got depressed caused by chronic stress.Compared with the normal group,the loss of weight of model group rats first appeared in the third week of modeling,the decrease of spontaneous activities of model group rats first appeared in the fifth week of modeling,the decrease in preference of sugar water of model group rats first appeared in the sixth week of modeling.Part two.Compared with the normal group,the expression of miR-124-3p in DG region of the model group showed bilateral change in the process of got depressed.The content of miR-124-3p in DG region of the model group increased in the fifth week and the sixth week of modeling,while the content decreased in the seventh week and the eighth week of modeling.Part three.Compared with the normal group,The number of Brdu/DCX?NeuN positive cells of the model group rates decreased significantly in the eighth week of modeling of process of got depressed caused by chronic stress.Part four.Observe the Brdu/DCX double standard fluorescence experiment results.Compared with the normal group,the ratio of the GOF model group was not significantly changed,while that of the LOF model group was significantly decreased.Part five.Observe the Brdu/Nestin double standard fluorescence experiment results.Compared with the normal group,the ratio of the LOF model group was decreased,while that was intervened by JWSNS was significantly increased.Conclusions:Part ole.The chronic unpredictable stress rat model can lead to abnormal expression of miR-124 in DG region,with two-stage changes of phased elevation and decrease.Part two.The decreased content of miR-124 may be partly responsible for the obstacle in proliferation and differentiation of neural stem cells.Part three.JWSNS can regulate the obstacle in proliferation and differentiation of neural stem cells due to the decreased content of miR-124. |
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