Research On The Changing Biorhythm Of Fei-we-qi Deficiency Syndrome And Intervention By Compound Based On Metabonomics

The theory of Fei-Wei(肺卫), as an important part of Traditional ChineseMedicine (TCM), has been expounded in Huang-di Nei-jing(黄帝内经)andlaid its basic academic ideas and theoretical framework at the same time.Wei-qi(卫气) refers to the qi that Fei governs, and the main function of whichis to resist exogenous pathogenic factors, warm the skin, open and close thesweat pore. The Fei (肺) governs qi and disperse Wei-qi to body surface toagainst invaded. Wei-qi bases on Fei-qi and relies on its dispersing. Theirfunctions are closely related to each other, so they are collectively called the"qi of Fei-Wei"(QFW) generally.With the continuous development of modern research and clinical practice,physicians and scholars gradually realize the importance of QFW on humanbody. Therefore, study on QFW has a great guiding significance to preventand cure disease. Recently, some scholars tried to explain the essence of QFWvia the modern technology. The theories such as immune andthermometabolism are connected with the material basis of QFW and docontribute to the improvement of the theory.But these theories explained QFW from its segmentary function and lackedcomprehensive elaboration of its material basis. The theory of Fei-Wei, underthe guidance of “the integration concept” and “correspondence between manand nature”, considers that QFW shows rhythmic changes which are due tobeing affected by natural sunlight, temperature and other exogenousinfluences. But the studies on endogenous substance basic and regulatorymechanism study of Fei-Wei rhythm are less studied up to now and remain tobe further discussed. More should to be done by using the new technology platform in the new technical level. Metabonomics technology provides agood starting point.Metabonomics is a new branch of system biology after the rise of genomics,transcriptomics and proteomics. It is a kind of technology that studies themetabolic network of biological systems by investigating the metabolite mapand its dynamic change before or after the biological systems is stimulated ordisturbed (such as a particular genetic mutation or environmental changes).Regardless of the complicated interactions among biochemical molecules andchanges in metabolic process, metabonomics has analyzed comprehensivelythe terminal product of metabolic as a whole in a diversified way and showedthe changes of organic inner state. It avoids using a single or a few indicatorsto research a certain pathological and physiological changes. With the holistic,dynamic and comprehensive characteristics, this analysis method is in linewith the integrity principle of TCM.For the first time, we break the framework which searches the essence ofQFW from its single function, using metabonomics technology to study thechange of endogenous metabolism by medicine interference along withFei-Wei rhythm changes. We expect to discover the small molecular metabolicmarkers of Fei-we-qi deficiency syndrome (FWQDS) through comparing thepatients with FWQDS before and after being invented by YuPingFeng Granule(玉屏风,YPFG). Furthermore, to select the material classification and scopeconsistent with the Fei-Wei rhythm, providing a new method to diagnose andtreat the respiratory system disease related to Fei-Wei.This paper mainly includes two parts: the theory and experiment.Part1Overview Resarch on Fei-Wei TheroyObjective: Summarize the understanding, research results andexploration of the Fei-Wei syndrome useing new technology platform throughthe overview of Fei-Wei theory.Method: Elaborate the relationship between Fei and Wei, the materialbasis, function, year rhythm of QFW, the pathological basis of FWQDS, andfeasibility of study Fei-Wei syndrome via metabonomics and so on. Conclusion: At present, researches of QFW focus on searching theessence from single function rather than exploring the material method fromthe circadian rhythms. Therefore, it is difficult to fully interpret the essence ofit. The range of material base of QFW should be studied further in an overalland comprehensive level. The metabonomics technology provides thepossibility.Part2Experiment and Clinical Researchs on FWQDSExperiment1Curative Efficacy Observation of Yupingfeng Granule inTreating the Patients of Recurrent Upper Respiratory Infection withFei-Wei-qi deficiency syndrome (FWQDS)Objective: Evaluate the clinical efficacy of Yupingfeng Granule (YPFG)in treating the patients of recurrent upper respiratory infection (RURI) withFWQDS by means of observing its influence on the clinical syndromes, totaleffective.Method: Forty cases of FWQDS were recruited as treated group, YPFGwas given as an intervention; twenty-two cases as controlled group,Thymopentin (TP-5) was given as intervention. Two months is one therapeuticcourse. The integral of symptoms were recorded respectively before and aftertreatment.Results: After60days the clinical symptoms of treated group improvedsignificantly(P＜0.01), upper respiratory infection(URI)numbers reducedclearly(P＜0.01),the total-clinical effective rate was92.5%.The clinicalsymptoms of controlled group improved obviously(P＜0.01,P＜0.05), URInumbers reduced clearly(P＜0.01),the total-clinical effective rate was90.9%.The change of clinical symptoms,URI numbers and the total-clinical effectiverate of the two groups have no statistical significance (P＞0.05).Conclusions: YPFG and TP-5both have good effect in treating thepatients of RRI with FWQDS. The curative effect is similar. This observationprovides a solid clinical support to in-depth study on our paper.Experiment2Studies of Plasma Metabonomics on Fei-Wei-Qi DeficiencySyndrome Patients which are Intervened by Yupingfeng Granule Objective: Use metabonomics methods to study the patients of recurrentupper respiratory infection with FWQDS and intervened by YupingfengGranule (YPFG) thus disproving the reliability of the possibly existentbiomarkers.Methods: Eighty-five cases of FWQDS were recruited as sick group,YPFG was given as intervention, two mouths is one therapeutic course; Ahealthy control group (eighty-five cases) was set up at the same time．Theblood was collected respectively on patients in control group and sick groupbefore and after treatment. The plasma metabolites were detected using highperformance liquid chromatography-mass spectrometry (HPLC-MS),statisticaldata were analyzed by principal component analysis (PCA) and partial leastsquares (PLS).The original spectrum and data of plasma metabolites werecompared among the three groups．Results: The metabolic spectrum before treatment in sick group wassignificantly different with control group.L-Cystein, L-Leucine, L-Methionine,L-Threonine and Pyroglutamic acid were inferred as possibly potentialsyndrome biomarkers of FWQDS at first. The spectrum showing regressivetrend to control group after the patients were intervened by YPFG. L-Cysteine,L-Methionine, L-Threonine and Pyroglutamic acid showed callback to controlgroup after treatment but L-Leucine deviated from control group further.Conclusions: There are positive changes in the metabolic profiling of thepatients with FWQDS which intervened by YPFG. L-Cysteine, L-Methionine,L-Threonine and Pyroglutamic acid showed callback after the patientsreceived treatment and were disproved their reliability as possibly potentialsyndrome biomarkers of FWQDS, correcting the amino acid metabolismdisorder may be one of mechanisms of YPFG in treating FWQDS at themolecular level.Experiment3Research on year biorhythm of Fei-Wei-qi DeficiencySyndrome Based on the Plasma Metabonomics Objective: Study the Plasma metabonomics characteristics of Fei-Wei-qideficiency syndrome (FWQS), and explore the potential syndrome biomarkersalong with its year biorhythm.Methods:23cases,17cases,15cases,30cases of FWQS were recruitedas sick groups respectively in spring, summer, autumn, and winter.26cases,10cases,18cases,31cases of health people were set as control groupscorrespondently. The blood was collected respectively from sick groups andcontrol groups in every season. The plasma metabolites were detected usinghigh performance liquid chromatography-mass spectrometry(HPLC-MS),Statistical data were analyzed by principal component analysis (PCA) andpartial least squares (PLS).The original spectrum and data of plasmametabolites were compared among the two groups in every season.Results: The potential syndrome biomarkers of FWQDS were inferredrespectively in spring, summer, autumn and winter, such as L-Cysteine,L-Methionine, L-Leucine, L-Aspartic acid, L-Homocysteine and others.Among these markers, L-Cysteine and L-Methionine can be found in fourseasons and are strong in spring and summer, weak in autumn and winter. Thistrend conformed to the year biorhythm of FWQS.Conclusions: There were not exactly the same potential syndromebiomarkers in every season. This result is associated with biorhythm ofFei-Wei. L-Cysteine and L-Methionine were inferred as the potentialbiomarker along with the year biorhythm of FWQDS.