| Depression has the characteristics of high prevalence rate,high suicide rate and high economic burden.At present,more drugs with better efficacy and less adverse reactions are still needed to enrich the treatment.Traditional Chinese medicine has nearly a thousand years of experience in the treatment of depression-related diseases such as yuzheng,visceral irritability,plum core qi and so on.Traditional Chinese medicine treatment can reduce the occurrence of adverse reactions and improve patients' compliance.This study systematically collates the ancient and modern literature related to depression syndrome and depression,summarizes and refines the treatment principles and methods of physicians of previous dynasties,and combines the clinical experience of mentors to create Tianxin Jieyu prescription,which is the principle of warming Yang and relieving depression and the five internal organs are in harmony with each other.And achieved a good effect in clinical observation,In the preliminary clinical observation,the effective rate is about 80.4%.Based on its better clinical effect,to explore its effectiveness,safety,mechanism and characteristics of efficacy.Objectives:1.Systematically collate the ancient literature,modern literature traditional Chinese medicine treatment of depression and depression treatment ideas and experience,to provide theoretical support for the treatment of depression2,To explore the efficacy,safety,therapeutic characteristics and mechanism of Tianxin Jieyu prescription,so as to provide data support for further clinical research.Methods:1.Literature research.1.1 Literature study on the treatment of depression syndrome with ancient Chinese medicine.Search multiple databases such as "Chinese Medical Code"(5th edition),TCM Resource Network,TCM Family,TCM Ancient Books Full-text Database,etc.The search was based on keywords such as "Yu Zheng","Zang Zao","Meiheqi",and"Baihe disease".Relevant sentences were entered into Excel 2017 by reading the date,source,author,symptom,treatment method,formula name,drug composition,etc.one by one to construct the ancient literature database of depression.Summarize and analyze the treatment ideas and experience of depression syndrome.1.2 Literature study on the treatment of depression with modern traditional Chinese medicineThe Chinese Knowledge Network and Wanfang database were searched,and the key words 'depression' or 'Yu Zheng' and 'traditional Chinese medicine' were used to search the original clinical studies published in the past ten years.Requires compliance with TCM syndromes or syndrome types,symptoms,treatment methods,complete prescriptions,and sample size? 60 cases.The types,syndromes,symptoms,prescriptions,etc.were entered into Excel 2017 to build a modern literature database of depression,and to summarize and analyze depression treatment ideas,experiences,and similarities and differences compared with ancient times.1.3 Summary of pathogenesis and treatment of depression.Through the previous literature research results,combined with the experience of doctors of previous dynasties and the progress of modern medicine,this paper briefly summarizes the pathogenesis and treatment of depression,in order to provide theoretical support for the treatment of depression.2.Experimental research.2.1 Study on Target Prediction of Tianxin Jieyu prescription based on Network PharmacologyObtain the active ingredients and targets of 11 flavors of Tianxin Jieyu prescription,obtain the disease targets of depression,and connect the two to obtain the possible antidepressant targets of Tianxin Jieyu prescription.Use cytoscape software to analyze these targets for KEGG pathway and GO Biological annotation,predicting the possible anti-depression pathways and targets of Tianxin Jieyu prescription.2.2 Experimental study of Tianxin Jieyu prescription on chronic reserpine-induced depression in rats.The treatment ideas of the listed drugs are similar to ours and the composition of the drugs are similar to those of warming the kidney group,soothing the liver group,soothing the liver and invigorating the spleen group.The rats after behavioral screening were randomly divided into blank group,model group,Tianxin Jieyu group,western medicine group,warming kidney group,soothing the liver group,soothing the liver and invigorating the spleen group,with 10 rats in each group.The model was made by intraperitoneal injection of chronic reserpine,and the drug was given at the same time.The body weight,behavioral test,the content of monoamine transmitters in serum and hippocampal HE staining were compared to explore the effectiveness and efficacy of Tianxin Jieyu prescription.Immunohistochemistry and western bold analysis were used to verify the mechanism of network pharmacology prediction targets.2.3 Preliminary study on the Safety of Tianxin Jieyu prescriptionAccording to the experimental procedure of animal feeding for 30 days,the rats were randomly divided into a blank group,a low-dose group,and a high-dose group of 9 rats each.The low-dose group was administered with a normal concentration of Tianxin Jieyu prescription,and the high-dose group was administered with a 4-times concentration of Tianxin Jieyu prescription.After 30 days of gavage,the general conditions,blood routine,blood biochemistry,important organ coefficients,and differences in liver HE staining were compared among the rats in each group,and whether the values fluctuated within the 95%normal range to verify the safety of Tianxin Jieyu prescription.Results:1.Literature research results1.1 Summary of the origin and connotation of medication based on ancient literature Yu Zheng evidenceFrom the perspective of development sources,Chinese medicine's understanding of Yu Zheng is a process of gradual development and perfection,which originated in the Warring States Period,developed in the Qin and Han dynasties,was perfected in the Jin and Yuan dynasties,and flourished in the Ming and Qing dynasties.From the perspective of conceptual connotation,the related concepts of Yu Zheng include three aspects of meaning,narrow Yu Zheng,broad Yu Zheng,which belong to process but not concept.The ancient doctors 'treatment of Yu Zheng has changed with the years,and most people think that the stagnation of spleen and stomach is the cause of Yu Zheng,which is related to the ancient doctors' experience and the characteristics of the ancient Yu Zheng.The theory that kidney yang deficiency is the cause of depression has also gone through the budding stage from the Warring States Period to the early Ming and Qing dynasties.In ancient times,the medicinal properties of Yu Zheng were mainly Wenping,and the flavor was mainly Xingan.Guijing was related to the five internal organs.Most of them were treated from the spleen,lung and heart,and the main treatment ideas were Jianpi Liqi.1.2 Summary of treatment ideas and medication characteristics of depression based on modern literatureDifferent from the causes of Yu Zheng,most of the causes of modern depression are Yang deficiency and Qi stagnation,and the common pathological products are blood stasis,phlegm and fiery fever.Different from Yu Zheng treatment ideas,the modern treatment of depression is mostly based on liver,spleen and kidney,and the main drug thinking is to clear the liver and qi,and the prescription is based on the addition and subtraction of Chaihu class prescriptions.These are more in line with the characteristics of modern depression Crowd characteristics.Like Yu Zheng,modern depression is still closely related to the five internal organs of Chinese medicine.1.3 Summary of pathogenesis and treatment of depression.According to the results of literature research and the progress of modern medical research,Yang deficiency and qi depression and five internal organs imbalance are the important pathogenesis of depression,warming yang and dispersing depression and five internal organs are the important treatment of depression,at the same time,attention should be paid to the treatment of blood stasis and phlegm.2.Experimental results2.1 Target prediction results of Tianxin Jieyu prescriptionTianxin Jieyu prescription based on clinical efficacy acts on 44 active ingredients such as ?-sitosterol,kaempferol,luteolin,quercetin,berberine and scopolamine,and acts on IL-6,NF-KB,CREB,ADRB2,BDNF Waiting for 28 effective targets,it is possible to up-regulate neurotrophic factor-related pathways including CAMP signaling pathway and neurotrophin signaling pathway,down-regulate related pathways of inflammatory factors including IL-17 signaling pathway and TNF signaling pathway,and up-regulate serotonin The synapse can increase the release of monoamine transmitters and play a role in treating depression2.2 Experimental study of Tianxin Jieyu prescription on chronic reserpine-induced depression in rats.2.2.1 effects of each administration group on body weight changes and behavior test of depressed ratsCompared with the model group,the Wenshen group and the Shugan Jianpi group can significantly restore the weight of the rats(P<0.01),and increase the horizontal exercise score(P<0.001)and vertical exercise score(P<0.001)in the open field experiments of rats(P<0.05)and total distance score(P<0.001),reducing the time of forced swimming in rats(P<0.05).The Shugan group could significantly restore the body weight of the rats(P<0.05),increase the horizontal exercise score(P<0.001)and the total distance score(P<0.001)in the open field experiments.In addition to improving the above indicators,the Tianxin Jieyu group increased the horizontal exercise score,vertical exercise score,and total distance of the open field experiment(P<0.05)and shortened the duration of forced swimming(P<0.001)Group,Shugan group,Shugan Jianpi group were more obvious.Can also shorten the tail suspension time(P<0.05).2.2.2 effects of different administration groups on serum cytokines in depressed rats.Compared with the model group,the Wenshen group,Shugan group,Shugan Jianpi group and Tianxin Jieyu group increased the levels of monoamine transmitters DA and 5-HT(P<0.001)in the serum,and Tianxin Jieyu group(P<0.001)and the warm kidney group(p<0.01)can increase the CAMP content in the serum of rats,but there is no significant change in the Shugan group and the Shugan Jianpi group(P?0.05).2.2.3 effects of different administration groups on pathological sections of hippocampus in rats with depression.Compared with the model group,the number of hippocampal cell layers in the warm kidney group and Shugan Jianpi group increased to 3-4 layers,with an orderly arrangement,looseness,and mild cell degeneration or atrophy.The number of hippocampal cells in the Shugan group was not significantly increased by 2-3 layers,and the arrangement was disordered,loose,and the cells degenerated or atrophied.The number of hippocampal cell layers in the Tianxin Jieyu group increased to 3-4 layers,and the cells were arranged in an orderly and compact manner,and the cells were slightly degenerated.2.2.4 effects of different administration groups on the expression of related targets in the brain of depressed rats.Compared with the model group,Tianxin Jieyu recipe can increase the expression of PKA in the cortex,promote the expression of CREB in the hippocampus,and decrease the levels of IL-6,IL-1? and TNF-? in the hippocampus.In Tianxin Jieyu group,the expression of BDNF,PKA and ADRB2 protein in hippocampus was significantly increased,while the expression of NF-kB protein was significantly decreased.Compared with the model group,warming kidney group could increase the level of PKA in cortex,soothing liver and invigorating spleen group could reduce the level of TNF-? in hippocampus,warming kidney group and soothing liver group could reduce the level of IL-6 in hippocampus,warming kidney group,soothing liver group and soothing liver and invigorating spleen group could reduce the level of IL-1 ?,but had no significant effect on other targets.2.3 preliminary exploration results of the safety of Tianxin Jieyu prescription.After 30 days of administration,compared with the blank group,the blood routine indexes(including HGB,WBC,RBC,PLT,MONO)of Tianxin Jieyu prescription low dose group and high dose group had no significant change(P>0.05).There were no significant changes in liver function(including ALT,TP,AST,ALB,TBIL,ALP,G),renal function(including UREA,BUN,UA,CREA),blood glucose(GLU)and blood lipid(TCH).There was no significant change in important organ index(including heart index,liver index,spleen index,lung index,kidney index and stomach index)(P? 0.05).And the values fluctuate within the normal range of 95%.The pathological sections of the liver showed that the hepatic lobules were clear and intact,the hepatic sinusoids were not congested and dilated,and the hepatocytes were not denatured and necrotic.Conclusion:1.Yang deficiency and qi depression and disorder of the five internal organs are the important pathogenesis of depression.Based on the relevant theory of the five elements of traditional Chinese medicine,kidney yang deficiency leads to liver qi stagnation,irritability,hypochondriac distension and other symptoms;water can not control fire,make heart fire flourish,palpitation,insomnia and other symptoms;Wood Sheng Ketu,damage spleen soil,appear stunned,worried and other symptoms;soil does not give birth to gold,heart fire Kejin,so that lung qi deficiency,sadness,cough and other symptoms;Gold does not boil water,which further aggravates the deficiency of kidney yang,while deficiency of yang qi encourages the inability to appear three low symptoms such as depression and slow thinking,which in turn affects the function of the brain and leads to the occurrence of depression.Yang deficiency and qi stagnation for a long time will affect the operation of qi and blood,resulting in pathological products of blood stasis,turbid phlegm and fiery heat.Based on the characteristics of the long attack cycle of depression,taking both the symptoms and the root causes,warming Yang to reach depression and five internal organs with the same tone as the important treatment of depression,at the same time,we should pay attention to the treatment of blood stasis,turbid phlegm and fiery heat,which is more in line with the disease characteristics of depression and the overall concept of traditional Chinese medicine.2.Tianxin Jieyu prescription may up-regulate the CAMP/PKA/CREB/BDNF signal pathway and down-regulate the IL-17/NF-KB signal pathway through berberine,kaempferol,luteolin,quercetin and other active ingredients to promote nerves The secretion of trophic factors,regulates neural plasticity,increases the proliferation and regeneration of neuronal cells,reduces inflammatory factors,inhibits abnormal activation of the immune system,and thus exerts antidepressant effects.3.Based on clinical efficacy,Tianxin Jieyu prescription has a good antidepressant effect on the depressive rat model of chronic reserpine injection in the experiment,and has no obvious adverse effects on normal rats in the experiment.It is better than fluoxetine in open field experiments,tailless experiments and brain hippocampus.4.Tianxin Jieyu prescription based on Wenyang Sanyu and Wuzang Tongtiao is more effective in treating liver depression,warming kidney,or invigorating the spleen than in treating liver spleen.The characteristics and advantages are worthy of clinical promotion and application. |
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