| As the development of systme biology ,we find that the philosophy of system biology and Traditional Chinese Medicine(TCM) is the same. In the theory and practice of traditional Chinese medicine (TCM), the human body is recognized as a whole system and the status of health or diseases is considered as the balance status of that system[1]. As the terminal of system biology,metabonomics,defined as"the quantitative measurement of the multiparametric metabolic response of living systems to pathophysicological stimuli or genetic modification"[2], is a novel methodology arising from the post-genomics era for the study of molecular systems biology. The strategy of metabonomics coincides with TCM theory and may play an important role in the modern study of TCM. In this study a metabonomic approach is employed for investigation of an animal model induced by a high dose of hydrocortisone, and the therapeutic and metabonomic effects of LWDHT.The first step was to apply the NMR approach and pattern recognise methods : principal components analysis(PCA) and partial least squares-discriminatory analysis(PLS-DA) technique to investigate the fluctuation of metabolites among the kidney-deficiency syndrome rats,the normal rats and the LWDHT treated rats. the results indicated that changes following hydrocortisone intervention of rats could be identified using PCA and PLS-DA, and, the'kidney deficiency syndrome (Shenxu Zheng) rats entered into a state of"hyperfunction", at the end of modeling experiment ,the rats entered a state of slow metabolic pattern, involving a series of changes in metabolic pathway and metabolic network, The response integral area of lactic acid(δ1.37) raised,which indicate the metabolic of lactic acid went into accumulation. The amount of sarcosine(δ3.87) raised which indicate that the disorder of kidney function is concerned with kidney deficiency syndrome. The response of dimethylamine(δ2.718),asparaginic acid(δ2.831), taurine(δ3.44,3.28), hippurate(δ7.84,7.56,3.97) decreased significantly, which indicated that the hydrocortisone cause the adrenal cortex's excreted function injured; The respones integral area of succinate(δ2.41) and citric acid(δ2.53,2.68) stepped down which indicate the mitochondria entered into disordered state. At the same time, we also investigated the blood plasma of the 3 groups rats by the same instrument and data processing way. The result indicated that there are three different metabolic patterns. The metabolism of"shen xu"(kidney deficiency syndrome) rats changed obviously, meanwhile,the LWDHT treated group did not change obviously as the former group,that is to say ,the LWDHT play a role in recovering the abnormal metabolism of rats.The second step was to apply the LC-MSn approach and pattern recognise methods: principal components analysis(PCA) and SOM,Fussy Classical technique to investigate the fluctuation of metabolites among the kidney-deficiency syndrome rats,the normal rats and the LWDHT treated rats. the results indicated that changes following hydrocortisone intervention of rats could be identified using PCA ,SOM,Fussy classical.we try to apply different PR methods to deal with the metabonomic data.we find that each PR method is special and helpful.The third step was to apply the LC-TOF/MS approach and pattern recognise methods: principal components analysis(PCA) and partial least squares-discriminatory analysis(PLS-DA) technique to investigate the fluctuation of rats urine metabolites among the kidney-deficiency syndrome rats,the normal rats and the LWDHT treated rats. the results indicated that changes following hydrocortisone intervention of rats could be identified using PCA and PLS-DA, and ,the kidney deficiency syndrome rats entered into a state of"hyperfunction", at the end of modeling experiment ,the rats entered a state of slow metabolic pattern, involving a series of changes in metabolic pathway and metabolic network, we found four bimarkers followed PR, tryptophane,sinapyl alcohol, hippuric acid,N1-Methyl-2-pyridone-5-Carboxamide,the amount of trytophane increased indicates that the biochemical pathway of the biosynthetic of catecholamines shift up.the area of hippuric acid rised indicate that the phenylalanine metabolic disordered.At the same time ,we also investigated the blood plasma of the 3 groups rats by the same instrument and data processing way. The result indicated that there are three different metabolic patterns. The metabolism of"shen xu''(kidney deficiency syndrome) rats changed obviously, meanwhile,the herb treated group did not change obviously as the former group,that is to say, the Liu Wei Di Huang Tang play an important role in recovering the abnormal metabolism,there are two biomarkers were found follow the PR.one of them is 1-Palmitoyl-sn-glycero-3-phosphocholine ,and the other is LysoPC.Both of the them are lipide,which is in agreement with the general opinion that glucocorticoids promote lipolysis.The forth step was to apply the GC-MS approach and pattern recognise methods to investigate the fluctuation of metabolites among the kidney-deficiency syndrome rats,the normal rats and the LWDHT treated rats. the results indicated that changes following hydrocortisone intervention of rats could be identified using PCA and PLS-DA, and ,the kidney deficiency syndrome rats entered into a state of"hyperfunction", at the end of modeling experiment, the rats entered a state of slow metabolic pattern, involving a series of changes in metabolic pathway and metabolic network. A number of marked changes were observed on the GC-MS chromatograms of urine following hydrocortisone treatment.It is noted that the raised tyrosine maybe a representation of drug-induced acceleration of the biosynthetic pathway of catecholamines .elevated some free fatty acids observed post-dose are in agreement with the general opinion that glucocorticoids promote lipolysis.There are three different analysis methods have been used to analyse the rats body liquids,urine and blood plasma, then the spectroscopy result deal with chemometrics ,the results indicates that the control, model, treatment group are distinguished obviously. There are some kinds of biomarker of kidney deficiency syndrome founded in the complex body liquid. Some of them are part of special metabolism pathway are identified, and which can be considered as the marker of the disease, for many kinds of disease can be judged by other methods except by the metabolites identification. At the same time, the traditional medicine Chinese (TCM) herbs called the Liu Wei Di Huang Tang(LWDHT) were used to treatment the rats which got the disease named"shen xu", we also investigated the effect of the herbs.the result indicate that the herbs called LWDHT play an important role in recovering the abnormal metabolic pattern in rats.The aim of the paper is to establish metabonomics method to study the"shen xu"and LWDHT. the work suggests that the metabonomic approach could be used as a potentially powerful tool to investigate the biochemical changes of certain physiopathologic conditions, the research results provides evidences for understanding of"Shen xu"in traditional Chinese medicine(TCM),and for diagnosis and therapy of this kind of disease in clinic. we believe that the metabonomis methods will be widely and deeply used in the research of modern biology and medicine fields in the future. |
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