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Effect Of Shugan Jieyuyin On Behavior, Activity Of Na~+-K~+-ATPase In Myocardium And MAO In Serum Of Depression Model Rat

Posted on:2011-03-20Degree:MasterType:Thesis
Country:ChinaCandidate:T T WangFull Text:PDF
GTID:2144360305454423Subject:Traditional Chinese Medicine
Abstract/Summary:PDF Full Text Request
Depression is a common emotional disorder, mainly as significant and persistent mood depressed, interest lacked, pessimistic, thinking torpid, self- accusation and self-incrimination, poor diet and sleep, physical unwell feelings, often associated with cognitive or mental function disorders, or a number of physiological changes, in severe cases, suicidal thoughts and behavior can occur. Modern people in 21st century, because of work and unemployment pressure, economic hardship and other reasons, often grow tense, tired and depressed, which leads to the occurrence of depression eventually. World Health Organization Study found that depression has become Chinese second-largest cumbrous disease, and predicted it will become the major killer of human in the 21st century. Therefore, depression has become the hotspot that world medical studies to capture.In recent years, research about pathogenesis of depression and antidepressant is gradually deepening. At present, the researches of depression pathogenesis are mainly about the following aspects: monoamine neurotransmitters, neuroendocrine, lipid peroxidation, and immune function. According to the current antidepressant effects or chemical structure,it can be divided into the following categories: monoamine oxidase (MAO) inhibitor, tricyclic antidepressants, selective 5-HT reuptake inhibitors, 5-HT and NE reuptake inhibitors, etc. Although the study of depression pathogenesis is comparatively in-depth, but Na~+-K~+-ATP enzyme and MAO associated with depression have been few studied. Na~+-K~+-ATP enzyme is a transmembrane protein, which can transport Na~+, K~+ in order to maintain the permeability of cells, keep cell volume, provide nerve impulses transmission and neurotransmitters release. Studies have shown that depression and mania associated with decrements in the activity of the Na~+-Ka~+-ATP enzyme membrane pump.MAO is an insolubility enzyme, which exists on the outer membrane of mitochondria of various types of cells in various organs of vertebrates, and its activity is related to the function of mood- regulating monoamine neurotransmitters. In this experiment, Shugan Jieyuyin is a Chinese medicinal formulae that was Addition or subtraction of the Conference form the old Chinese classical prescription"Chaihu Shugan San"and"Xiaoyao San"by Professor Li Youtian of the First Hospital of Jilin University, with the efficacy of soothing liver-qi stagnation, nourishing the heartand soothing the nerves, strengthening the spleen and stomach, nourishing blood and liver, clearing heat and relieving fidgetness. In the long-term clinical practice, most patients'depression, anxiety, insomnia and other symptoms of depression were improved significantly after taking Shugan Jieyuyin, and this has indicated that the Chinese medicinal formulae is a curative effect significant, stable, safe and reliable prescription. The aim of this study is to analyze the mechanism of SGJYY from the Na~+-K~+-ATP enzyme and MAO activity point of view, and explore the significance of MAO in the pathogenesis of depression.Methods: 48 healthy male and female half and half clean Wistar mice were used as experimental animals, adaptive feed 3 days, in which time monitored and recorded body weight, the number of horizontal and vertical movement, and the sucrose consumption, before divided into six groups random, including healthy control group, disease model control group, prozac group, SGJYY large dose group, medium dose group and small dose group. All the groups except healthy control group mice were induced and established the model of depression by isolated supporting and chronic unpredictable moderate intensity stimulation within 28 days. In the modeling process, we monitored body weight weekly to determine each group rat's appetite and weight loss status. After 28 days of continuous stimulation, each modeling group rats were listlessness, poor appetite, and the average weights were significantly lower than healthy controls. Monitoring the number of horizontal and vertical movement and the sucrose consumption on the 28th day, the result showed that they were all significantly lower than healthy controls. All the above indicate that the rat models of depression have been successfully copied, and the levels of depressive symptoms in each group were similar so as to be used in subsequent experiments.After the model of depression in rats had been successfully copied, the rats were uninterruptedly dosed 28 days by intragastric administration, at the dosage of each 2ml, 1 time per day. In addition to the model control group rats were given the same volume of saline, SGJYY large, medium and low dose groups were given 8g/ml, 4 g / ml, 2g/ml, which were calculated as clinical concentration of 2 times, 1 times and 1/2 times. We select clinical common antidepressant "Prozac" as contrast, according to " the formula of dose equivalent conversion ratio by the body surface area between animals and humans " to calculate the daily dose in rats was 0.36mg/ml, that 20mg fluoxetine would be dissolved in 110 ml normal saline solution in the preparation of 0.18mg/ml. The rats'body weights were needed to monitor every week during this process. After 56 days dosing, we monitored the number of horizontal and vertical movement and the sucrose consumption. Then blood was taken by cardiac puncture, centrifuged 5minitues in low self-poise centrifuge at 2500rev/min, then serum was isolated, placed in -70℃refrigerator after split charging. The rat apical mood, the outer membrane of left ventricular myocardial tissue, preparation of tissue homogenate, the homogenate to 1000rpm/min low speed centrifugation for 5 minutes and the supernatant frozen at -70℃refrigerator.The results showed that, before the drug treatment, in addition to the healthy control group, the others'body weight grew slowly, behavior number scores and sucrose consumption were reduced (compared with the control group, P<0.05). After drug treatment, the fluoxetine group, Shugan Jieyuyin large and middle dose group body weight, behavior number scores and sucrose consumption were increased (compared with the model control group, P <0.05); and compared with healthy control group, there were no significant differences (P>0.05). These results suggest that Shugan Jieyuyin has obviously antidepressant effect. In addition, by colorimetric assay kit detected and calculated, compared with the healthy control group, myocardial Na~+-K~+-ATP enzyme activity of model control group reduce, and serum MAO activity increased (P<0.05); compared with model control group, myocardial Na~+-K~+-ATP enzyme activity of SGJYY large and medium dose and Prozac group was significantly increased, while serum MAO activity decreased significantly (P<0.05), compared with the healthy control group, there was no significant difference (P>0.05). Statistical result points out Shugan Jieyuyin can increased myocardial Na~+-K~+-ATP enzyme activity and reduce serum MAO activity of depression model rat.In conclusion, Shugan Jieyuyin can play an antidepressant effect on increasing Na~+-K~+-ATP enzyme activity and inhibitting MAO activity, thus it plays an important role in the clinical treatment of depression. The result also explain change of Na~+-K~+-ATP enzyme activities is significant related to the pathogenesis of depression have an important relationship. This study also confirms the "monoamine neurotransmitter hypothesis", and proves that there is a link between changes of MAO and occurrence of depression. This research can not only be regarded Experimental basis of Shugan Jieyuyin treating depression, but also provide a new direction and new ideas for further follow-up study.
Keywords/Search Tags:Shugan Jieyuyin, depression, depression rat model, Na~+-K~+-ATP enzyme, monoamine oxidase
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