| Purpose1.On the premise of sorting out the ancient literature,according to the relevant theory of TCM prescription and syndrome,the clinical literature in the past ten years was sorted out by data statistics method,in order to excavate the corresponding relationship of Shengyang Yiwei Decoction.2.Combining with metabolomics,which is an important component of modern system biology,the differential metabolites of fatigue model rats and normal rats were searched.On this basis,the regulation mechanism of modified Shengyang Yiwei Decoction and its disassembled recipes on chronic fatigue rats was discussed,which provided scientific basis for clinical treatment of chronic fatigue syndrome with modified Shengyang Yiwei Decoction.3.According to the theory of traditional Chinese medicine,Shengyang Yiwei Decoction was divided into two groups,and the difference of metabolic pathways of blood and urine in chronic fatigue model rats was compared between the whole group and each group,which added new scientific contents to the study of compatibility of prescriptions and metabolomics of prescriptions and syndromes.Methods:1.To sort out the different understanding of Shengyang Yiwei Tang prescription and prescription compatibility among doctors in ancient literature,and on this basis,using the databases of China HowNet,Wanfang and Weipu as retrieval databases,the clinical literature and medical case literature published in various domestic medical journals and magazines in recent ten years were selected and analyzed by literature information mining method.2.The model group reproduced the fatigue rat model by compound stimulation(cold water swimming + diet control + tail-clamping stimulation).The general behavior changes,blood biochemical indexes,monoamine neurotransmitters,gastrointestinal function indexes and hematuria metabolic map of rats in blank group and model group were observed dynamically.3.According to the previous literature research and the related theory of prescription and syndrome,the decoction was divided into group A(the whole Decoction group),group B(the whole Decoction group),group C(the whole Decoction group),group D(the whole Decoction group).The changes of general behavior,blood biochemical parameters,monoamine neurotransmitters,gastrointestinal function,energy metabolism and hematuria metabolic profiles were observed in rats treated with modified Shengyang Yiwei recipe and separated prescriptions.Results:1.The results of text mining of Shengyang Yiwei Decoction show that it is widely used in internal medicine,gynecology,surgery and facial diseases.Among them,digestive system diseases were the main diseases(34.4%).It has the functions of Invigorating Qi and yang,invigorating spleen and dispelling dampness,and harmonizing liver and spleen.It is a prescription for the coordination of liver,spleen and lung.Its clinical differentiation is mainly based on discomfort of limbs,fecal discharge,frequency of urination,lack of food,fatigue,dull complexion,pale tongue coating,white fat,big teeth marks,weak pulse,which is consistent with the clinical manifestations of chronic fatigue syndrome.2.The experimental results of rats with chronic fatigue model constructed by complex factors showed that there were changes of physical exhaustion,anger,depression and despair in the process of modeling.Serum BUN increased significantly(P < 0.01),5-HT,DA and NE contents in hypothalamus decreased significantly(P < 0.01),D-xylose excretion rate and MT content decreased(P < 0.01),and VIP increased first and then decreased(P < 0.01).3.The results of hematuria Metabonomics Study in fatigue model rats showed that the disturbance of serum metabolism induced by compound stimulation was mainly related to the following metabolic pathways:(1)biosynthesis of valine,leucine and isoleucine(impact= 1.0);(2)synthesis and degradation of ketone body(impact = 0.60);(3)metabolism of dicarboxylic acid(impact = 0.30);(4)glycine,tryptophan And threonine metabolism(impact= 0.29);(5)pyruvate metabolism(impact = 0.19);(6)citric acid metabolism(impact = 0.13).Urine metabolic disorders in fatigue rat models duplicated by compound stress are mainly related to the following metabolic pathways:(1)taurine and taurine metabolism(impact =0.43);(2)dicarboxylic acid metabolism(impact = 0.30);(3)pyruvate metabolism(impact =0.24);(4)tricarboxylic acid cycle(impact = 0.15);(5)carbohydrate regeneration(impact =0.13).4.Study on the mechanism of Shengyang Yiwei Decoction and its decomposition in intervening chronic fatigue:(1)The results of blood biochemical index experiment showed that the serum BUN content of model rats could be reduced by adding or subtracting Shengyang Yiwei Formula,but the serum BUN content of model rats in each disassembled formula group had no effect.In addition,the serum Cr content of model rats could be increased in each administration group,but the effect of adding or subtracting Shengyang Yiwei Jianpi Formula on the serum CR content was weaker than that of other administration groups.(2)The results of monoamine neurotransmitter test showed that the DA content and5-HT content in hypothalamus of model rats could be increased in each group.(3)The experimental results of gastrointestinal function indicators showed that the D-xylose excretion rate of model rats could be increased in all groups,and the effect of group A and C and D on D-xylose excretion rate was better than that of group B.The MTL content of model rats was increased in all groups(P < 0.01);the VIP content of model rats was inhibited in all groups,and the MTL secretion formula was promoted in group B.Compared with other groups,group D was superior to other groups in inhibiting VTP elevation.The results showed that the combination of soothing liver and regulating qi with removing dampness and reducing turbidity could promote the secretion of MTL,while the combination of Tonifying Qi and invigorating spleen with soothing liver and regulating qi could inhibit the increase of VIP.(4)The experimental results of energy metabolism indicators showed that the ATPase activity in skeletal muscle tissue of rats in the model group was significantly decreased,and the SDH activity and FFA concentration were significantly increased after stimulation with compound factors,suggesting that the energy metabolism of rats in the model group was disordered.Adding or subtracting Shengyang Yiwei Decoction could increase ATPase activity and significantly restore SDH and FFA levels in model rats.(5)Metabonomic studies showed that there were some differences in the metabolic pathways affected by anti-fatigue among the groups.The serum metabolic pathways in thewhole prescription group include the biosynthetic pathways of valine,leucine and isoleucine;the metabolic pathways of glycine,serine and threonine;the butyric acid metabolic pathway,the tricarboxylic acid cyclic metabolic pathway,the pyruvate metabolic pathway,the glycogenesis pathway,the ketone body synthesis and degradation and the dicarboxylic acid metabolic pathway;the urine metabolic pathway also involves the taurine and taurine metabolism.Access.The differences of metabolic pathways among the groups were as follows: in the blood metabolic pathway,the metabolic pathways of glycine,serine and threonine,pyruvate and carbohydrate metabolism in group B(whole prescription reducing Qi and invigorating spleen group)showed transitional callbacks;in group D(whole prescription reducing dampness,removing turbidity and reducing turbidity group),the metabolic pathways of dicarboxylic acid showed transitional callbacks,while the three decomposed prescriptions showed transitional callbacks.No effect on the cyclic metabolic pathway of tricarboxylic acid was found in group A.In the urine metabolic pathway,group D(the group of all prescriptions reducing dampness and turbidity)showed transitional regression effects on dicarboxylic acid cycle,tricarboxylic acid cycle and pyruvate metabolism.Conclusion:1.Compound stress factors were more likely to show fatigue and cognitive behavioral changes than single stress factors.The causes of CFS were simulated from both physical and psychological perspectives,which also accorded with the clinical manifestations of "spleen deficiency" and "liver depression" syndrome in TCM.Therefore,this compound stress modeling method can better reflect the integrity of the body.2.There were disorders in gastrointestinal function,central nervous system,sugar metabolism,amino acid metabolism and energy metabolism in fatigue model rats.The anti-fatigue mechanism of Shengyang Yiwei Decoction may be through reducing the accumulation of metabolites,regulating the functions of central nervous system and gastrointestinal tract,promoting sugar metabolism,energy metabolism and amino acid metabolism.3.The study on decomposition of Shengyang Yiwei Decoction found that the Yiqi Jianpi Pharmaceutical Team played an important role in influencing gastrointestinal function,among which the Shugan Liqi compatibility Qushi Jiangzhuo group was helpful to promote the secretion of MTL,while the Yiqi Jianpi compatibility Shugan Liqi method was helpful to inhibit the rise of VIP.Metabonomics study found that there were some differences in the metabolic pathways affected by the decomposition groups of Shengyang Yiwei Decoction.The three prescription compatibility teams play a stable and balanced role in the metabolism pathway of blood tricarboxylic acid cycle.Among them,the group of eliminating dampness and reducing turbidity had greater influence on the metabolic pathway in urine.The differential expression of hematuria in model rats in the above decomposed prescription groups provides a research direction for us to further study the compatibility of prescriptions. |
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