| Depression is a common mental disorder,with low mood and loss of pleasure as its main clinical feature.It is accompanied by restless sleep,poor appetite,loss of interest in daily activities,inability to concentrate,inferiority and suicidal thoughts.According to statistics,at least 16 million 100 thousand people in the United States have experienced depressive episodes in 2015,and the incidence of depression has reached 6.7%.Although the commonly used antidepressants are effective,there are many problems such as low cure rate,prominent symptoms,high recurrence rate,and prominent functional damage.From the perspective of traditional Chinese medicine,we can find out the treatment therapy of depression and study its mechanism,which can effectively improve the treatment effect of depression and provide more options for the treatment of depression.Traditional Chinese medicine has the characteristics of multipath,multilevel and multi target.It can be used to treat depression with good effect.Chinese medicine believes that the basic pathogenesis of depression is "liver depression",and the basic therapy is soothing the liver.Combining the idea of the famous doctor Wang Ji,which is that "Regulate and nourish qi and the blood,Strengthen the basic cultivation of Qi".Our project is to study the antidepressant effect and its mechanism of Peiyuan Jieyu Fang,which is the combined formula of Tiansi Yin and Sini San.The previous study has studied the effect and mechanism of Tiansi Yin,Sini San and Peiyuan Jieyu Fang.On this basis,this experiment used pharmacodynamic model to evaluate the Peiyuan Jieyu Fang comprehensive.1 The effect of Peiyuan Jieyu Fang on reserpine antagonistic experiment miceObjective:To study the antidepressant effect of Peiyuan Jieyu Fang on reserpine(RR)mice.Methods:RR model was established in mice by the peritoneal injection of reserpine with a dose of 2.5mg/kg,observe the influence of Peiyuan Jieyu Fang in temperature,ptosis of eyelid,rate of ring out of the RR model mice.Results:Peiyuan Jieyu Fang each dose could antagonize the RR model mice decreased body temperature(P<0.01),in addition,high doses can also improve the reserpine induced ptosis,akinesia condition(P<0.05),middle dose can improve the condition of akinesia(P<0.05).Conclusion:Peiyuan Jieyu Fang has antidepressant like effect on the RR model.2 The effect of Peiyuan Jieyu Fang on acute stess model miceObjective:To study the antidepressant effect of Peiyuan Jieyu Fang on acute stress model,and to explore the mechanism of antidepressant effect.Methods:Using FST to establish the acute stress model in mice,to observe the effect of Peiyuan Jieyu Fang on forced swimming time of FST model.Enzyme-linked immunosorbent assay(ELISA)was used to detect the contents of 5-serotonin(5-HT),norepinephrine(NA)and indolamine-2,3-double oxygenase(IDO)in mice of FST.Results:The medium and low dose group of Peiyuan Jieyu Fang could shorten the immovable time of FST model mice(P<0.05,P<0.01),and significantly increase the content of 5-HT and NA in the brain(P<0.05,P<0.01).There was no statistical difference in the content of IDO in each group.Conclusion:Peiyuan Jieyu Fang has antidepressant effect on FST model,the mechanism may be related with increasing 5-HT and NA contents of monoamine neurotransmitters in the brain of mice.3 The effect of Peiyuan Jieyu Fang on chronic stress model miceObjective:To study the antidepressant effect of Peiyuan Jieyu Fang on chronic stress model mice,and to explore its mechanism of antidepressant effect.Methods:chronic stress model was established by long-term bondage and noise stimulation,to observe the influence of Peiyuan Jieyu Fang on forced swimming time of mice with chronic stress model.The content of 5-HT and IDO in the brain was detected by ELISA,and the expression of IDO mRNA in the brain was detected by fluorescence quantitative PCR.Results:The high,medium and low dose of Peiyuan Jieyu Fang could significantly shorten the immovable time in forced swimming of chronic stress model mice,increase the content of 5-HT in brain tissue,and decrease the content of IDO and the expression of IDO mRNA(P<0.05).Conclusion:Peiyuan Jieyu Fang has some effect to improve the depressive symptoms of mice caused by chronic stress.4 The effect of Peiyuan Jieyu Fang on chronic unpredictable stress ratsObjective:To study the antidepressant effect and mechanism of Peiyuan Jieyu Fang on chronic unpredictable stress rats.Methods:The rats were given daily stimulation to establish chronic unpredictable stress model.And model was evaluated by open field test and sucrose preference test.The positive expression of glucocorticoid receptor(GR),5-HT1A receptor,N-methyl-D-aspartate receptor 1(NMDAR1)in rat hippocampal was detected by immunohistochemistry,and the positive expression of Ki67 and GFAP,Ki67 and Neun in the hippocampus of rats was detected by immunofluorescence.Results:Peiyuan Jieyu Fang can increase open field activity and sucrose preference of the chronic unpredictable rat,and the difference was statistically significant.Compared with the model group,GR in hippocampus of Peiyuan Jieyu Fang high dose group the average optical density value was significantly increased and the number of positive cells was increased(P<0.01,P<0.05).5-HT1AR average optical density in each dose group of Peiyuan Jieyu Fang has the downtrend,but the difference was not statistically significant.The average optical density of NMDAR1 is obviously reduced in the midum and high dose group of Peiyuan Jieyu Fang.There was no significant difference in the positive expression of Ki67 and GFAP,Ki67 and Neun in hippocampus of each group.Conclusion:Peiyuan Jieyu Fang has antidepressant effect on chronic stress rats,and it is related with increasing the expression of GR,restraining the level of NMDAR in the hippocampus.5 The effect of Peiyuan Jieyu Fang on chronic stress combined with lipopolysaccharide depression model miceObjective:To study the antidepressant effect of Peiyuan Jieyufang on chronic stress combined with lipopolysaccharide depression model mice,and to explore its mechanism of antidepressant effect.Methods:The composite model was established by injecting lipopolysaccharide 10mg/kg into mice after restraint and noise stimulation for 10d.Observe the effects of Peiyuan Jieyu Fang on immobility time in forced swimming of chronic stress combined with lipopolysaccharide depression model mice.The content of IL-1 beta,TNF-alpha and IFN-gamma in serum,and the content of IFN-gamma in the brain were detected by radioimmunoassay.The content of interferon gamma in the brain was detected by ELISA,and the concentration of free calcium ion was detected by flow cytometry.Results:Tiansi Yin,Sini San and Peiyuan Jieyu Fang are able to shorten the immovable time in forced swimming of composite model mice(P<0.05).The content of TNF-alpha and IFN-gamma in the serum of model mice can be reduced by Tiansi Yin and Peiyuan Jieyu Fang.The content of IL-1 beta and IFN-gamma in serum of model mice can be reduced by Sini San.Compared with model group,the content of IFN-gamma in the brain of mice in the group of Tiansi Yin,Sini San and Peiyuan Jieyu Fang showed no significant difference.The brain cells' Ca2+ levels in the group of Tiansi Yin,Sini San and Peiyuan Jieyu Fang trend to decreased,but no statistically significant difference compared with the model group.Conclusion:Tiansi Yin,Sini San and Peiyuan Jieyu Fang has certain antidepressant effect on chronic stress combined with lipopolysaccharide depression model.Tiansi Yin,Peiyuan Jieyu Fang can exert antidepressant effects through inhibiting the pro-inflammatory cytokines TNF-alpha,IFN-gamma.Meantime,the antidepressant mechanism of Sini San associated with reducing the level of IL-1 beta,TNF-alpha. |
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