| Depression is the main type of affective mental disorder. It is a syndrome with significant and persistent depressed mood, accompanied by corresponding abnormal thoughts and behaviors. Patient with depression is self melancholy, pessimistic, and even has suicidal tendency. According to the latest investigation of World Health Organization (WHO), the global incidence of depression is about 11% and the depression has already been the fourth major diseases in the world.In recent years, with the development of immunology, people have realized that the role of immune activation in the pathogenesis of depression. Immune activation is often accompanied with kinds of cytokines production, however uncontrolled cytokine production could also cause damage to the body. In 1991, Smith et al. reported for the first time that the depression was associated with the abnormal secretion of cytokines. With many researches and investigations in this field, peoples raised a"Cytokine Hypothesis of Depression", that the depression might be caused by abnormal cytokines produced by the activated immune cells.SGJYY is a Chinese traditional medical prescription derived from the well known"Shugan powder"and"Xiaoyao powder". It could relieve the liver pen, safeguard stomach against damages and soothe the nerve. SGJYY has been widely used in the clinical treatment of depression, and achieved excellent effect. The symptoms of depression patient treated with SGJYY, such as depression, anxiety, insomnia were ameliorated remarkably. The purpose of this study is to analyze the mechanism of SGJYY from the immunological point of view andexplore the significance of inflammatory cytokines in the pathogenesis of depression.In this study, healthy male Wistar mice were used as experimental animals and randomly divided into six groups, including healthy control group, disease model group, SGJYY large dose group, middle dose group and small dose group, prozac group. All the mice except healthy control group were used to establish the model depression by separate feeding and long-time chronic unpredictable moderate intensity stimulation. During this process, to judge the mental state of the mice, we tested the sugar water consumption and the body weight regularly and used Open-field experiment to monitor the scores of horizontal and vertical movement. After 28 days of continuous stimulation, all the model mice were found to have obvious depressed symptoms, such as low appetite and significant loss of body weight. The consumption of sugar water and the scores of movement were also less than the mice in healthy control group. These results demonstrated that the depression model mice had been established successfully. The symptom of each mouse is similar and all the mice could be used for the subsequent experiments.At the 28th day after the beginning of establishing the depression model, the model mice were treated with indicated agents through intragastric administration for another 28 days, 2 ml per mice, one time a day. The dose of SGJYY was determined in accordance with the clinical project. The SGJYY solution was boiled and evaporated to high concentration for the large dose group, or diluted with PBS for the small dose group. Base on the formula of dose equivalent conversion ratio by the body surface area between animals and humans. During the treatment, separate feeding and chronic unpredictablemoderate intensity stimulation were still kept until the end of experiment. In this process, the body weight and consumption of sugar water were tested regularly,and the Open-field experiment was conducted to monitor the scores of horizontal and vertical movement. At the 56th day, the mice were sacrificed by removing the eyeball. Then the blood was collected for the isolation of serum and the serum was stored at low temperature until use. The brain tissue was also isolated from the mice, and the weight of the brain tissue was examined and recorded. Then the brain tissue was prepared for homogenate and stored at low temperature until use.The level of TNF-α, IL-2 in serum and 5-HT in brain tissue were main index in this experiment. TNF-αis an important pro-inflammatory cytokine, it could mediate the chronic inflammatory response. IL-2, mainly produced by activated T cells, is necessary for T cell proliferation and mediated the Th1 type immune response. IL-2 is not only important for the immune regulation, but also associated with the Th1 type immune diseases. 5-HT is an important monoamine neurotransmitter. According to the neurotransmitter hypothesis of depression, lack of 5-HT in central nervous system might lead to the occurrence of depression. The sandwich ELISA and fluorescence spectrometer were conducted to detect the levels of TNF-α, IL-2 in serum and 5-HT in the homogenate of brain tissue. The therapeutic effect and the mechanism of SGJYY on the treatment of depression were analyzed in accordance with the level of TNF-α, IL-2, 5-HT, the body weight, the sugar water consumption and the scores of behavior.The result showed that, comparing with the healthy control group, the depression model mice grew slowly and the behavior scores and sugar waterconsumption also decreased significantly before the SGJYY treatment. The depression model mice were in a panic, fear and despair state. The results of sandwich ELISA showed that the levels of TNF-αand IL-2 in serum of depression model group were higher than that of healthy control group. This result indicated that the increasing of inflammatory cytokines might lead to depressive disorders, suggesting the depression is associated with abnormal immune activation. The behavior score and sugar water consumption of depression model mice were remarkably increased compared with the depression model group after SGJYY treatment. Moreover, the content of TNF-αand IL-2 in serum decreased significantly, whereas the 5-HT in brain tissue increased. The symptoms of depression model mice were also improved.In summary, this study analyzed the underlying mechanism of SGJYY on the treatment of depression from the immunologic point of view. The curative effect of SGJYY attributes to the decreasing of inflammatory cytokines level to some extent, suggesting SGJYY improved the symptoms of depression model mice and treated patients with depression through regulating the immune system and suppressing the secretion and activity of certain inflammatory cytokines, such as TNF-α,IL-2. In addition,this study supported the"Cytokine Hypothesis of Depression", revealing the relationship between inflammatory cytokines and depression. This study not only provided valuable experimental data for the treatment of depression with traditional Chinese medicine, but also introduced a new direction for the research and development of novel traditional Chinese medicine on depression.
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