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Serum Metabolomics Study Based On Rat Model Of Metabolic Syndrome Of Spleen And Kidney Yang Deficiency Syndrome

Posted on:2017-05-20Degree:MasterType:Thesis
Country:ChinaCandidate:X J TianFull Text:PDF
GTID:2354330485497113Subject:Chinese medical science
Abstract/Summary:PDF Full Text Request
Purpose:Metabolic Syndrome is a combination of risk factors including obesity,high blood sugar,dyslipidemia,hypertension, which can seriously affect the health of the body. These factors are directly contributed to the occurrence of atherosclerotic cardiovascular disease and increase the risk of type 2 diabetes. The experimental research, through the establishment of Yang deficiency of spleen and kidney metabolic syndrome rat model, the combination of TCM theory and metabolic group study method, and comparison with blank control group and spleen kidney yang deficiency model group, comparison and analysis of the serum samples in two groups, looking for Yang deficiency of spleen and kidney metabolic syndrome lesions characteristic of a metabolite, through the observation of the metabolite changes with physiological and pathological correlation, to explore the spleen kidney yang deficiency syndrome, metabolic syndrome, the molecular mechanism of lesions, further revealing the spleen kidney yang deficiency syndrome, metabolic syndrome essence.Material and method:1 spleen kidney yang deficiency rat model replicationWistar healthy male rats of clean grade, body weight (220±20) g, the adaptive feeding for a week before the experiment, free drinking water, no adverse reactions, eating, drinking and activities of the normal subjects into the experiment. According to body weight were randomly divided into blank control group (n=8), daily intake of normal rats feed, drinking tap water, free feeding, water intake. Model group (n=28), the 1-4 weeks, according to 10 mg/(kg·d) dose given to rats with 0.1% propylthiouracil, the 5-18 weeks,in Yang deficiency of spleen and Kidney Foundation on the basis of using the method of continuous feeding with high glucose and high fat diet combined with small doses of STZ, the establishment of MS rat model, the whole cycle modeling for 18 weeks.2 The research of metabonomics8 rats with syndrome of deficiency of spleen and kidney yang deficiency syndrome with deficiency of spleen and kidney yang deficiency were randomly selected and 8 rats were randomly selected as control group. Using the Agilent company gas chromatography (GC TOF MS based) instrument coupled with chromatography time of flight mass spectrometry, using the SIMCA software (V14 umetrics AB, Umea, Sweden) on the normalized data for pattern recognition multivariate analysis, principal component analysis using UV (UV variable scaling) format for processing the data scale conversion. The automatic modeling and analysis of data. Then the model correction orthogonal partial least squares discriminant analysis (OPLS-DA), maximum internal model and forecast highlights principal component (Predictive component) related differences. OPLS-DA uses the Par format (Par Scaling) data scale conversion, on the first, the two principal component analysis model. Finally, through the OPLS-DA analysis to filter out the orthogonal signal not related to the differences of metabolites thus obtained is more reliable.Results:1 Spleen kidney yang deficiency rat model replication:Compared with the blank control group rats, model group rats from the gavage administration began, feeding, reduce the amount of water,1 week after polyuria, weight loss in individual rats, after 4 weeks of reduced activity, lazy to move like get together, stool soft pond, perianal dirt, individual rectal prolapse phenomenon, strong odors, spiritual malaise, fatigue, hair gloss gradually faded, yellow teeth. After 6 weeks of weight of rats in the model group and blank control group was significantly increased compared there were significant differences between the two groups (P <0.01), of which eighth weeks had no statistical significance (P>0.05). After 6 weeks in control rats fasting glucose compared with the control group, increased significantly, there were significant differences between the two groups (P<0.05), after 12 weeks between the two groups had significant difference (P<0.01). After 8 weeks model group triglyceride and blank rats compared with the control group, increased significantly, there are significant differences between the two groups (P<0.01). The rats in the model group with high density lipoprotein compared with the control group, decreased significantly after 4 weeks between the two groups there are differences (P<0.05), after 8 weeks between the two groups had significant difference (P<0.01). After making model after (week 18) in the model group rats serum insulin and the normal control group was significantly higher than that, there is a difference between the two groups, the insulin sensitivity index decreased significantly, insulin resistance index increased significantly, between the two groups exist difference (P< 0.05). After the end of the modeling (week 18) in the model group rats serum levels of FT3 and FT4 levels with the blank control group decreased compared, there is a difference (P< 0.05) between the two groups, and serum TSH levels were significantly increased, between the two groups exist difference (P<0.05). After making the mould temperature level and the blank (week 18) in the model group rats of control group decreased compared, between the two groups exist difference (P<0.01). At the end of Modeling Rats with evaluation of spleen kidney yang deficiency syndrome of metabolic syndrome in this study intends to establish the standard.2 Metabolomics studies:by OPLS-DA, the model group rats and the blank control group could be divided into two groups, and there was no obvious cross and overlap between the two groups.3 Potential biomarkers:to find and yang deficiency of spleen and kidney metabolic syndrome rat model associated with potential biological marker compounds, mainly for Maleic acid,Fumaric acid,N-Ethylmaleamic acid,Ethyl cinnamate,L-Cysteine,Creatine,alpha-Ketoglutaric acid,1,2,4-Benzenetriol,Tartaric acid,L-Phenylalanine,Xylitol,beta-Glycerophosphoric acid,Ribitol,Glucose-1-phosphate,Gentisic acid,4-Nitrophenyl phosphate,N-Carbamyl-L-glutamate,N-Acetyl-D-galactosamine,Uric acid,N-Acetyl-beta-D-mannosamine and other, a collection of these substances together constitute the spleen kidney yang deficiency syndrome, metabolic syndrome rat model of metabolomic profiles.Conclusion:1 Through drug (0.1% propylthiouracil) diet intervention and Festival (high sugar and high fat diet) and low dose STZ injection molding method is to copy the success of spleen kidney yang deficiency syndrome of metabolic syndrome rat model.2 Experimental Study on the distribution of metabolic syndrome of Yang deficiency syndrome in spleen deficiency syndrome of spleen deficiency syndrome of spleen and kidney in rats by metabolic syndrome.3 It is discovered that the syndrome of Yang deficiency of spleen and kidney metabolism of N Maleic acid,Fumaric acid,N-Ethylmaleamic acid,Ethyl cinnamate,L-Cysteine,Creatine,alpha-Ketoglutaric acid,1,2,4-Benzenetriol,Tartaric acid,L-Phenylalanine,Xylitol,beta-Glycerophosphoric acid,Ribitol,Glucose-l-phosphate,Gentisic acid,4-Nitrophenyl phosphate,N-Carbamyl-L-glutamate,N-Acetyl-D-galactosamine,Uric acid,N-Acetyl-beta-D-mannosamine and other comprehensive syndrome rat model of potential biological markers, reveals the Yang deficiency of spleen and kidney metabolism comprehensive syndrome occurrence of carbohydrate, lipid and protein metabolism related, and these small molecules in vivo compounds may for metabolic syndrome the material basis of TCM syndrome.4 Metabonomics which researches into the mechanism of diseases and syndrome essence in traditional Chinese medicine in depth is the important method.
Keywords/Search Tags:Metabolic syndrome, Rat model, Yang deficiency of spleen and kidney, Metabonomics
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