| The theory of five elements’ motion and six kinds of natural factors is a concentrated expression of the holistic view of "integration of man and nature" in Chinese medicine.Yunqi theory believes that the occurrence of diseases is affected by the gasification of the world,so the characteristics of Yunqi should be fully considered when diagnosing and treating diseases.Guided by the theory of the five elements’ motion and six kinds of natural factors,Chen Wuze made 16 prescriptions of the five elements’ motion and six kinds of natural factors,which have been used clinically in later generations and have many extraordinary effects,and become the representative in the past to guide clinical medication with Yunqi.However,most of the current researches on Yunqi prescriptions are reports on clinical trials,and there is a lack of systematic animal experimental studies.This study uses the clinical common mental illness depression as an entry point,and uses Chen Wuze’s Sitian prescriptions as interventional prescriptions to compared the antidepressant effect of Yunqi prescriptions on depression model rats in different years,so as to excavate the important value of Yunqi theory for clinical diagnosis and treatment,and provided scientific basis for the clinical use of Yunqi prescriptions.The thesis is divided into three parts:The first part systematically sorts out the relevant literature of the clinical application of Chen’s Yunqi prescriptions,and discovers some problems in the research,and provides a reasonable basis for the experimental design based on the Yunqi theory and the current status of depression treatment.The second part discusses the effects of changes of Yunqi on the occurrence of diseases and the treatment rules established according to the theory of drug properties,and discusses its guiding role in the creation of prescriptions related to Yunqi theory in later generations,focusing on the introduction of Chen Wuze’s Sitian prescriptions,which has a high clinical value,and the medication complies with the principles from The Inner Canon of Huangdi.The third part is the experimental part which adopts depressive rat model established by chronic unpredictable mild stress(CUMS)combined with separated living,and uses the Sitian prescriptions,Jingshun Decoction of Wuxu year in 2018 and Fuhe Decoction of Jihai year in 2019,as the intervention prescription,comparing with the clinical conventional antidepressant medicine fluoxetine and the commonly used classic prescription Chaiqinwendan Decoction.The therapeutic effect of the formula and medicine above on depression model in different years were evaluated by taking various behavioral experiments,and High performance liquid chromatography-electrochemical detection method(HPLC-ECD)was used to determine the Changes in the content of neurotransmitters and metabolites in brain and serum.The experimental results are as follows:1 Experiment 1:experimental results of Jingshun decoction in Wuxu year1.1 The effect of Jingshun decoction on the behavior of depression model rats1.1.1 Sucrose preference experimentAt the end of the experiment(42 days),compared with the blank group,the sucrose preference index of the model group was significantly reduced(P<0.01).Compared with the model group,the indexes of sucrose preference of the rats in fluoxetine group,Chaiqinwendan Decoction group and Jingshun Decoction group were significantly increased(P<0.01).1.1.2 Open field experiment At the end of the experiment(42 days),there was no statistically significant difference in the number of grid crossings of rats in the open field within 3 minutes between the groups(P>0.05).1.1.3 Forced swimming experiment Compared with the blank group,the model group’s forced swimming immobility time was significantly extended(P<0.01).Compared with the model group,the immobility time of forced swimming test of Fluoxetine group was significantly shortened(P<0.05),and the time of Jingshun Decoction group and Chaiqinwendan Decoction group was significantlyshortened(P<0.01).1.1.4 Tail suspension experiment Compared with the blank group,the immobility time of the tail suspension test in the model group was significantly prolonged(P<0.01).Compared with the model group,the immobility time of the tail suspension test of the Jingshun Decoction group and Chaiqinwendan Decoction group,was significantly shortened(P<0.01).1.2 The effect of Jingshun Decoction on the levels of monoamine neurotransmitters and metabolites in different brain regions and serum of depression model rats1.2.1 Changes in the levels of monoamine neurotransmitters and metabolites in the prefrontal cortexCompared with the blank group,the content of NE and 5-HT in the prefrontal cortex of the model group significantly reduced(P<0.05),and the content of DA was significantly reduced(P<0.01);compared with the model group,the content of 5-HT in Chaiqinwendan Decoction group increased significantly(P<0.05),and in Jingshun Decoction,the content of DA increased significantly(P<0.01),and the content of 5-HT increased significantly(P<0.05),There was no statistically significant difference in the content of E,HVA and DOPAC in the prefrontal cortex of rats between each two groups(P>0.05)1.2.2 Changes in the levels of monoamine neurotransmitters and metabolites in the hippocampusCompared with the blank group,the content of NE and 5-HT in the hippocampus of the model group was significantly reduced(P<0.01),and the content of 5-HIAA was significantly reduced(P<0.05);compared with the model group,the content of NE and DA in the hippocampus of the Chaiqinwendan Decoction group increased significantly(P<0.05),the content of NE and 5-HT of the Jingshun Decoction group increased significantly(P<0.01).There was no statistically significant difference of content of E,HVA and DOPAC in hippocampal of rats between each two groups(P>0.05).1.2.3 Changes in the levels of monoamine neurotransmitters and metabolites in the hypothalamusCompared with the blank group,the contents of DA in the hypothalamus of the model group were significantly reduced(P<0.05);compared with the model group and Chaiqinwendan Decoction group,the contents of DOPAC in the Jingshun Decoction group increased significantly(P<0.01).There was no significant difference in the content of NE,5-HT and their metabolites in the hypothalamus between each two groups(P>0.05).1.2.4 Changes in serum levels of monoamine neurotransmitters and metabolitesCompared with the blank group,the content of 5-HT and 5-HIAA was significantly reduced(P<0.01);compared with the model group,the content of 5-HT in the serum of rats of the Chaiqinwendan Decoction group increased significantly(P<0.05),and the content of 5-HT and 5-HIAA in the serum of rats of Jingshun Decoction group increased significantly(P<0.01);compared with the Chaiqinwendan Decoction group,the content of DA and 5-HIAA in the serum of rats of the Jingshun Decoction group increased significantly(P<0.05).2 Experimental results of Fuhe Decoction in Jihai year2.1 Effect of Fuhe Decoction on Behavior of Depression Model Rats2.1.1 Sucrose preference experimentAt the end of the experiment(42 days),compared with the blank group,the sugar preference index of the model group was significantly reduced(P<0.01).Compared with the model group,the sucrose preference indexes of the rats in the fluoxetine group,Chaiqinwendan Decoction group and Fuhe Decoction group increased significantly(P<0.01).2.1.2 Open field experimentAfter the experiment(42 days),compared with the blank group,the number of grid crossings in the model group significantly decreased(P<0.01);compared with the model group,the number of grid crossings of rats in Chaiqinwendan Decoction group,Jingshun Decoction group and Fuhe Decoction group tended to increase but the difference was not statistically significant(P<0.05).2.1.3 Forced swimming experimentCompared with the blank group,the immobility time of forced swimming in the model group tended to increase.Compared with the model group,the difference between the administration groups was not statistically significant(P>0.05).2.1.4 Tail suspension experimentCompared with the blank group,the immobilization time of the tail suspension experiment in the model group was significantly extended(P<0.01).Compared with the model group,the immobility time of rats in the fluoxetine group,Chaiqinwendan Decoction group,and Fuhe Decoction group was significantly shortened(P<0.01),the immobility time of rats in the Jingshun Decoction group was significantly shortened(P<0.05).2.2 The effect of Fuhe Decoction on the levels of monoamine neurotransmitters and metabolites in different brain regions and serum of depression model rats2.2.1 Changes in the levels of monoamine neurotransmitters and metabolites in the prefrontal cortexCompared with the model group,the content of DA in the prefrontal cortex of the rats in the Jingshun Decoction group increased significantly(P<0.05),and the content of 5-HT in the prefrontal cortex of rats of the Chaiqinwendan Decoction group and Fuhe Decoction group increased significantly(P<0.01),and the content of 5-HT in the prefrontal cortex of rats of the Fluoxetine group and Jingshun Decoction group increased significantly(P<0.05).The mean value of the Fuhe Decoction group was higher than that of the other administration groups.2.2.2 Changes in the levels of monoamine neurotransmitters and metabolites in the hippocampusCompared with the blank group,the content of 5-HIAA in the hippocampus of the model group was significantly reduced(P<0.01);compared with the model group,the content of 5-HT in the hippocampus of the rats of the Fuhe Decoction group increased significantly(P<0.05),and the mean value of the Fuhe Decoction group was higher than that of the other administration groups.2.2.3 Changes in the levels of monoamine neurotransmitters and metabolites in the hypothalamusCompared with the model group,thecontent of DA in the hypothalamus of rats of the Jingshun Decoction group and Fuhe Decoction group increased significantly(P<0.05);compared with the Chaiqinwendan Decoction group,the content of E in the hypothalamus of rats of the Jingshun Decoction group and Fuhe Decoction group increased significantly(P>0.05).2.2.4 Changes in serum levels of monoamine neurotransmitters and metabolitesCompared with the blank group,the content of E and 5-HT in serum of the model group was significantly reduced(P<0.05);compared with the model group,the content of 5-HT in the serum of rats of the Chaiqinwendan Decoction Group,Jingshun Decoction Group,Fuhe Decoction Group increased significantly(P<0.01).the content of HVA and 5-HIAA in serum of rats of the Chaiqinwendan Decoction group increased significantly(P<0.01),the content of 5-HIAA in serum of rats of Jingshun Decoction group increased significantly(P<0.05).Analyze the experimental results and draw the following conclusions:(1)Jingshun Decoction improved the depression-like behavior of rats induced by CUMS in 2018,which is the year of Taiyanghanshui Sitian,and it was more obvious than Chaiqinwendan Decoction group.Compared with Chaiqinwendan Decoction,which regulates qi and dissipates phlegm,Jingshun decoction is more effective.and the mechanism of its effect may be related to improving the level of DA and 5-HT level in prefrontal cortex,NE and 5-HT in hippocampus,and 5-HT in serum of model rats.(2)Fuhe Decoction improved the CUMS induced depression-like behavior of rats in 2019,which is the year of Jueyinfeng Sitian,which is more obvious than the other groups.The mechanism of its effect may be related to improving the level of 5-HT in prefrontal cortex,hippocampus and serum,and the level of DA in hypothalamus of model rats.(3)Jingshun Decoction and Fuhe Decoction all showed better therapeutic effects under the Yunqi conditions of the year,and the efficacy was slightly better than conventional antidepressant western medicine and traditional Chinese medicine,and the effect of treatment under the guidance of Yunqi theory is better than that of commonly used classic prescriptions,promting the influence of five elements’ motion and six kinds of natural factors on the occurrence of disease,and it has practical significance to guide clinical medication according to the characteristics of Yunqi. |
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