| Along with the increasing social competition and relieve the pressure of life lack technique,more and more people suffer from a serious disease of depression,looking for the early prevention and treatment means has become the primary issues in medical research.The clinical findings of depression to a certain stage of development,in addition to depression,loss of interest,there are other complicated symptoms of a variety of systems such as extreme fatigue,lazy lie,insomnia,forgetful,anorexia and epigastric discomfort.Wang Yongyan academicians believe that the pathogenesis of these characteristics is mainly related to liver qi stagnation and spleen deficiency and dampness closely.Flow data also showed that liver qi stagnation and spleen deficiency is an important pathogenesis and common syndromes of depression.The stagnation of liver qi stagnation and spleen deficiency often evolved.A classical theory and technology named "See the liver disease,know that the spleen will be involved,and need to strengthen the spleen first "has long-term guide the practice of emotional disease of traditional Chinese medicine,and also be thought as a typical example,but its dynamic evolution mechanism of the scientific connotation is not clear.Mitochondria are the "power plants" for the life activities of eukaryotic cells,and are the sites where the carbohydrate,fat and amino acids are ultimately oxidized to release energy.Mitochondrial damage can cause cell dysfunction and show multiple system involvement symptoms,which is highly consistent with the characteristics of extreme fatigue and multiple system symptoms in patients with liver qi stagnation and spleen deficiency.Studies have shown that the pathogenesis of depression is not only related to the mitochondrial energy metabolism disorders,but also with neuroendocrine disorders,immune inflammatory network disorders and other related.However,it is not clear how the regulation of neuroendocrine immune inflammatory network and mitochondrial damage in the pathogenesis of depression of liver qi stagnation and spleen deficiency.Chronic stress is the main cause and trigger condition of depression.Chinese medicine believes that stress affects the movement of qi,which is consistent with the pathogenesis of liver qi stagnation,stress in the later can see liver qi stagnation and its evolution,such as liver qi stagnation and spleen deficiency.According to modern stress theory,stress is the first cause of neuroendocrine disorder,which leads to multiple system dysfunction.Therefore,we propose that the important microscopic mechanism of liver qi stagnation and spleen deficiency pathogenesis of depression may be related to the disorder of mitochondrial energy metabolism and the imbalance of related neuroendocrine inflammatory network.This paper first carries on a preliminary exploration which detect the energy metabolism characteristics of liver qi stagnation and spleen deficiency in patients with depression,and further reveal the mitochondrial energy metabolism characteristics of liver qi stagnation and spleen deficiency of depression and the effect mechanism of traditional Chinese medicine through the animal experiment,to further enrich the scientific connotation of interpretation of depression of liver qi stagnation and spleen deficiency,provide an objective basis for clinical practice of traditional Chinese medicine for the prevention and treatment of depression.Clinical study:The levels of ATP,ADP and AMP in serum of patients with depression of liver qi stagnation and spleen deficiencyObjective:To explore the characteristics of energy metabolism in patients with depression of liver qi stagnation and spleen deficiency.Methods:There are three groups consist of the depression group of liver qi stagnation and spleen deficiency,the subthreshold depression group of liver qi stagnation and quality health group.Peripheral blood serum content of ATP ADP,AMP of three groups were detected by the method of HPLC,and were compared between groups.Result:Compared with the liver qi stagnation of subthreshold depression group,ATP content of depression group of liver qi stagnation and spleen deficiency decreased.Conclusion:Patients with depression of liver qi stagnation and spleen deficiency have energy metabolism disorder,which provides an objective basis for revealing the microscopic mechanism of depression of liver qi stagnation and spleen deficiency from the angle of energy metabolism disorder.Experimental study:To study the mitochondrial energy metabolism characteristics of liver qi stagnation and spleen deficiency of depression and the effect mechanism of Xingpi Jieyu decoction based on the model of CUMSObjective:To reveal the microscopic mechanism of liver qi stagnation and spleen deficiency of depression and to elucidate the effect mechanism of Xingpi Jieyu decoction through the correlation analysis of mitochondrial energy metabolism of depression rats of liver qi stagnation and spleen deficiency and its correlation of immune neuroendocrine inflammation index dynamic changes,.Methods:8 week old male Wistar rats were randomly divided into control group,model group,Chinese medicine low(3.6g/kg/d),Chinese medicine middle(7.2g/kg/d),Chinese medicine high(14.4g/kg/d)dose group,western medicine group(Seculin,4.5mg/kg/d),using CUMS methods last for 6 weeks,during the period of stress administered orally,on the sugar consumption test and forced swimming behavior assessment at 2 and 6 weeks,serum,skeletal muscle,hippocampus,duodenum were obtained and the mitochondrial damage index(mtDNA content,Ⅰ Ⅱ Ⅲ Ⅳ activity),mitochondrial biogenesis pathway index(the expression of SIRT1,PGC-1 protein)and THE energy index(ATP content,Na-K-ATPase activity,Ca-Mg-ATPase activity)and nerve endocrine immune inflammatory markers(CORT,TNFAlpha,gamma,IL-6,IL-4,IFN-γ IL-10)dynamic correlation between mitochondrial energy metabolism characteristics of model rats and the neuroendocrine immune index,reveal the microscopic mechanism of depression of liver qi stagnation and spleen deficiency,and to elucidate the mechanism of the effect of Xingpi Jieyu decoction.Result:1 The model of liver qi stagnation and spleen deficiency of depression:when the stress for 6 weeks,compared with the blank control group,the rate of preference of sugar in the model group was reduced,the immobility time of forced swimming was prolonged,and the depression rat model was established.According to the macro characterization(rat lazy,dry hair,loose stools/tail clamp increased defecation and body mass of slow growth),behavior(sucrose preference rate-anhedonia and immobility time-weary lazy),medicine(Xingpi Jieyufang)required to indicate the presence of liver qi stagnation and spleen deficiency.2 The changes of mitochondrial index,energy index and neuroendocrine immune index in rats2.1 Mitochondrial damage index-mtDNA,complex Ⅰ Ⅱ Ⅲ ⅣAt 2 weeks of stress:the activity of I in hippocampus of model group was significantly lower than that of control group.At 6 weeks of tress:compared with the control group,in the hippocampus,the content of mtDNA of the model group decreased significantly,complex Ⅰ Ⅲ Ⅳ activity decreased,in skeletal muscle mtDNA content decreased significantly,complex Ⅰ Ⅲ Ⅳ activity decreased,in the intestinal tissue,complex Ⅰ Ⅲ Ⅳ activity decreased..2.2 Mitochondrial biosynthetic pathway indicators-SIRT1,PGC-1 alphaAt 2 weeks of stress:compared with the blank control group,the expression of PGC-1 in skeletal muscle of model group was increased.At 6 weeks of stress:compared with the blank control group,the expression of SIRT1 and PGC-1 in hippocampus,skeletal muscle and small intestine were significantly increased in the model group.2.3 Energy indicators-ATP,Na-K-ATPase,Ca-Mg-ATPaseAt 2 weeks of stress:the Ca-Mg-ATPase activity in skeletal muscle of model group was lower than that of blank control group.At 6 weeks of stress:compared with control group,in the hippocampus,the content of ATP of the model group decreased,Na-K-ATPase and Ca-Mg-ATPase activity decreased,in skeletal muscle,the content of ATP decreased,Na-K-ATPase activity decreased,in small intestine,ATP content decreased,Na-K-ATPase activity decreased.2.4Neuroendocrine immune indexAt 2 weeks of stress:compared with the blank control group,the model group CORT,TNFalpha,IFN-gamma,IL-6 content increased,IL-10 content decreased.At 6 weeks of stress:compared with the blank control group,the model group CORT,TNFalpha,IFN-gamma,IL-6 content increased,IL-4,IL-10 content decreased.3 The intervention effect Xingpi Jieyu decoction3.1 Behavioral evaluationSugar consumption test:at 6 weeks of stress,compared with the model group,the intervention of Chinese medicine in each dose group and western medicine group,the rate of preference in sugar syrup increased,in which the middle dose of Chinese medicine was significantly higher than that in the western medicine group.Forced swimming test:at 6 weeks of stress,compared with the model group,the middle dose of chinese medicine can significantly shorten the time of forced swimming in rats.3.2 Mitochondrial damage index-mtDNA,complexⅠ Ⅱ Ⅲ ⅣAt 2 weeks of stress:compared with the model group,the middle,high dose of traditional Chinese medicine and western medicine group could increase the activity of complex Ⅰ.At 6 weeks of stress:compared with the model group,in the hippocampus,the low dose of Chinese medicine group can increase the content of mtDNA,enhance the activity of complexⅠ Ⅲ,the middle dose of traditional Chinese medicine group can increase the content of mtDNA,the high dose of traditional Chinese medicine group can increase the content of mtDNA,enhance the activity of comples Ⅲ Ⅳ,the western medicine group can increase the content of mtDNA,enhance the complex Ⅰ Ⅳ activity.In skeletal muscle tissue,the low dose of Chinese medicine group can enhance the activity of complex Ⅲ Ⅳ,the high dose of traditional Chinese medicine group can increase the content of mtDNA,enhanced Ⅰ Ⅲ Ⅳactivity,the western medicine group can increase the content of mtDNA,enhance the activity of complex III,in small intestine,the low dose of traditional Chinese medicine can enhance the activity of complex I IV,the middle dose of traditional Chinese medicine can enhance the activity of comples IV,the high dose of traditional Chinese medicine can enhance the activity of comples Ⅰ Ⅲ Ⅳ,the western medicine group can enhance the activity of complex Ⅰ Ⅲ Ⅳ.3.3 Mitochondrial biosynthetic pathway indicators-SIRT1,PGC-1 alphaAt 2 weeks of stress,there was no significant difference between the two groups.At 6 weeks of stress:compared with the model group,in the hippocampus,in the low,middle dose of traditional Chinese medicine group the expression of SIRT1 decreased,in the low,middle dose of traditional Chinese medicine group and western medicine group,PGC-1 expression decreased;compared with the model group,in skeletal muscle tissue,in the low,middle dose of traditional Chinese medicine group the expression of SIRT1 decreased,in the low,middle dose of traditional Chinese medicine group and western medicine group,PGC-1 expression decreased;in the small intestine,compared with the model group,in the low,middle dose of traditional Chinese medicine group and western medicine group,SIRT1 and PGC-1 expression decreased.3.4 Energy indicators-ATP,Na-K-ATPase,Ca-Mg-ATPaseAt 2 weeks of stress:compared with the model group,the skeletal muscle tissue of Western medicine group can increase the activity of Ca-Mg-ATPase.At 6 weeks of stress:compared with the model group,in hippocampus,the low dose of traditional Chinese medicine group can enhance Na-K-ATPase activity,the high dose of traditional Chinese medicine group can increase the content of ATP,enhanced Na-K-ATPase and Ca-Mg-ATPase activity,the western medicine group can increase the activity of Na-K-ATPase;compared with the model group,in skeletal muscle tissue,the high dose of traditional Chinese medicine group can increase the activity of Na-K-ATPase;compared with the model group,in small intestine,the western medicine group can increase the content of ATP.3.5 Endocrine immune indexAt 2 weeks of stress:compared with the model group,the middle dose of traditional Chinese medicine group can reduce CORT,IFN-gamma,IL-6 content,IL-10 content increased;the high dose of traditional Chinese medicine group can reduce the IFN-gamma and IL-6 content;the western medicine group can reduce CORT and IL-6 content,IL-10 content increased.at 6 weeks of stress:compared with the model group,the low dose of traditional Chinese medicine group can reduce CORT,TNF-alpha content;the middle dose of traditional Chinese medicine group can reduce CORT,TNF-alpha,IFN-gamma,IL-6 content,increase IL-4 and IL-10 content,the high dose of traditional Chinese medicine can reduce the CORT,TNFalpha,IL-6 content,IL-10 content increased;the western medicine group can reduce CORT,TNF-alpha,IL-6 content.Conclusion:1 In the hippocampus,skeletal muscle and small intestine of liver qi stagnation and spleen deficiency of depression rats,mitochondria damage,mitochondrial biosynthesis regulation,energy metabolism disorder and endocrine inflammation network disorder are exist.at 2 weeks of stress,endocrine inflammatory network has obvious disorder,at 6 weeks of stress,both endocrine immune disturbance,apparent mitochondrial damage,mitochondrial biogenesis pathway and abnormal energy metabolism disorder appeared.With the extension of stress time,the degree of injury gradually increased.2 In the process of stress induced depression,endocrine disorders and inflammation occurring in the first place,along with the stress,then appeared endocrine-inflammation network and mitochondrial energy metabolism.These characteristics meets the traditional Chinese medicine theory "See the liver disease,know that the spleen will be involved,and need to strengthen the spleen first",and the mitochondrial damage,mitochondrial biogenesis abnormal regulation and energy metabolism disorder is key pot of spleen deficiency syndrome elements.3 Based on the pathogenesis of liver qi stagnation and spleen deficiency,Xingpi Jieyu decoction play a protective effect of anti-stress injury through the angle of behavioral levels,molecular levels,gene level and signal pathway.Different dose of Xingpi Jieyu decoction have different effective characteristics.4 Both Xingpi Jieyu Decoction and sertraline can improve the mitochondrial energy metabolism and neuroendocrine-inflammatory indicators of depressed rats,however the effective characteristics are not the same,combined traditional Chinese medicine and western medicine can play a synergistic antidepressant effect. |
PDF Full Text Request