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Gloomy Particles Antidepressant Effect And Mechanism

Posted on:2008-10-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:X JinFull Text:PDF
GTID:1114360215473496Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Depression is a psychosis, which is characterized by various manifestations of affective disorder.It affects patients' working,learning and living so that they have difficulty adapting themselves to society, even induce suicidal behavior at last. With intense social competition and fast working pace, more and more people will feel tensive, exhausted and melancholy. Incidence rate of depression will show an upward tendency. Furthermore, relief of depression is related to the rehabilitation of body disease. Psychopathology of depression is not known. Treatment on depression that is based on the hypotheses has a variety of defects. Today,the research is focused on the pathogenesis of depression and the new drugs that are effective and have fewer side effects.On the basis of the traditional theories, traditional Chinese medicine (TCM) had played more and more important role in treating depression. Guided by TCM' s theories, combining with contemporary theories, experimental and clinical results of TCM and Western medicine, developing new Chinese herbal preparation with good curative effects and fewer side effects is a new project.It will be of great importance to improve the effect of TCM on treating depression and understand the mechanism of treating depression of classical prescriptions."Kaiyu Grain"is created to treat depression due to pathogenic fire derived from stagnation of liver-qi and phlegm-heat attacking the heart, accompanied by deficiency of the spleen. Our studies include prescription, pharmacy, action, toxicology and mechanism exploration.1 The demonstration of Kaiyu Grains' prescription2 Pharmacodynamics research of Kaiyu Grains2.1 Effects of Kaiyu Grains on Behavior despair of animal2.1.1 Effect of Kaiyu Grains on the tail suspension test with ratsThe findings revealed that Kaiyu Grains 12g/kg,8g/kg can significantly diminish the immobility time(P<0. 01, P<0.05 compared with control).2.1.2 Effect of Kaiyu Grains on the forced swimming test (FST) with ratsCompared with the results of each group in the FST, we found that Kaiyu Grain 12g/kg,8g/kg can significantly reduce the immobility time (P<0. 01, P<0.05 compared with control).2.2 Effect of Kaiyu Grains on the chronic stress depression model with ratsAfter chronic unpredictable stress(including: moistened breed, foot shock, swim in ice water, bake at 45℃, clip tail, day and night reverse, prohibit food for 24 hours, prohibit water for 24 hours) exerted on each rat excluding the control ones for 21 days, we found that the Kaiyu Grains can improve the symptoms appeared in the model rats. The Kaiyu Grains 12g/kg,8g/kg,4g/kg can signif- icantly antagonize slowly increasing of the model rats' body weight, increase the consumption of 1 percent sugar water(P<0.01, P<0.05 compared with control).The numbers of crossings and rearings in the open field test were increased as well.3 The research on mechanisms of Kaiyu Grains treating depression3.1 Kaiyu Grains ' effect on rats' brain 5-HT, NEThrough testing rat's brain single pendulum and metabolite by HPLC and ECD, we found that after dosing 21 days, Kaiyu Grains 12g/kg,8g/kg,4g/kg had distinct difference from the control group (p<0.01) in rat's brain's 5-HT, NE 's metabolite DOPAC; Kaiyu Grains in the group with large amount had distinct difference from the control group (p<0.01), the content of 5-HT and NE had increased; The result showed that dosing Kaiyu Grains for long may increase rat's brain's content of 5-HT, NE's metabolite DOPAC for the chronic stress stagnation of liver-energy rats. This way maybe is one of the mechanisms of anti-depression.3.2 The alteration of GIRK1 mRNA expression in the brain of depression rats.It showed that GIRK1 CA1, CA3 and dentate with control(P<0.05).GRRK1 mRNA expression significantly increased in gyrus of hippocampus and parietal cerebral cortex the CA1, CA3,compared with control group.3.3 The effects of Kaiyu Grains hippocampus of Chronic Mild Stress on BDNF expression at cortex and model ratsHE tincture: hippocampal pyramidal cells arranges tightly and neurone cell shape have no abnormalities in control rats.In model rats, cells arrange confused and raritas, most cells pyknosis and the number of cells reduced obviously. GYC could reduce cell damage.In BDNF immunohistochemical study, compared with control, the BDNF levels were decreased, the number of the BDNF positive cells was reduced and their color became lighter in model. Kaiyu Grains could elevate BDNF levels and positive cells, and improve the color of the cells in cortex and hippocampus.
Keywords/Search Tags:Antidepressant
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