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Inflammation In Phlegm Wet Individuals Related Mechanism Research

Posted on:2014-01-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:L Y ZhengFull Text:PDF
GTID:1224330398952826Subject:Basic Theory of TCM
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Recent studies have shown that metabolic syndrome is a systemic low-grade inflammation state, showing abnormalities and inflammatory signaling pathway for inflammatory cytokines. Phlegmy-wet constitution is a biased constitution whith the nature of heavy, sticky and stagnant. Based on the fore-working, Phlegmy-wet constitution and obesity are closely related, which may be the background and foreground factors of Metabolic Diseases. Whether the Phlegmy-wet constitution has been low-grade inflammation state without any disease, it is great significance to the regardless of the microscopic mechanism of dampness constitution prone to metabolic disorders, especially for the non-obese non-dampness constitution disease prevention. Choose113person the age between20~50year-old adults which were Cheeked-up erowd in PuRen hospital medical examination center between April to December in2011. Based on BMI, the participants were divided into five groups which included obesity Phlegmy-wet constitution (OBT) group (BMI≥24kg/m2)with30cases、non obesity Phlegmy-wet constitution (NOBT) group(BMI<24kg/m2) with25cases、 obesity non Phlegmy-wet constitution (OBNT) group(BMI>24kg/m2) with28cases、 normal (P)group(BMI<24kg/m2) with18cases and metabolic syndrome (MS) with10cases. Body mass, height and waist circumference (WC,cm)were measured, Analysis of its general information and biochemical test results, Preliminary study of Phlegmy-wet constitution groups associated with the metabolism of obesity and metabolic syndrome population. Then, choose obesity Phlegmy-wet constitution (OBT) group (BMI>24kg/m2)with30cases、non obesity Phlegmy-wet constitution (NOBT) group(BMI<24kg/m2) with25cases、obesity non Phlegmy-wet constitution (OBNT) group(BMI>24kg/m2) with28cases and normal (P)group(BMI<24kg/m2) with18cases. Serum levels of TNF-α IL-6、CRP and MCP-1were measured with luminex technique human obesity multianalyte profiling base kit. According to the preliminary study results, choose non obesity Phlegmy-wet constitution (NOBT) group and normal (P)group, use Affymetrix Human Genome U133Plus2.0gene chip to find Phlegmy-wet constitution specific gene expression, then use Panomics QGP(QuantiGene Plex) to establish the genes specifically expressed in non-obese Phlegmy-wet constitution.The main experiments performed were as follows:1. The baselines of the general data and general biochemical indicator were no different among the5groups, except MS group had a higher levels of biochemical indicator;2. BMI and FAT%of OB group were significantly higher than that of NOB group (all P<0.05):the TNF-α levels in serum of OBT group were significantly higher than the P group (p<0.01), and there was no statistical significance(all P>0.05) for IL-6; the CRP and MCP-1levels in serum of OBT、NOBT and OBNT groups were significantly higher than the P group (p<0.05,p<0.01); Phlegmy-wet constitution score was positively correlated with TNF-α、IL-6and MCP-1(p<0.05).3. Using the SAM (Significance Analysis of Microarrays), There were14genes up-regulated (>=2folds).8genes down-regulated(<=2folds)between NOBT and P. Then using the RMA find out There were82genes up-regulated (>=1.5folds),75genes down-regulated (<=1.5folds) between NOBT and P. By Arraytools tools to predict the classification of samples, there are seven classification prediction methods classification accuracy rate of more than90%. GeneGo analysis showed230and58differentially expressed genes between the NOBT and P groups. GoMiner analysis revealed that the differentially expressed genes between the NOBT and P groups were enriched during GO:0046519-sphingoid metabolic process, GO:0006665-sphingolipid metabolic process, GO:0003676-nucleic acid binding and GO:0019538-protein metabolic process etc. Gene array analysis of signal transduction in NOBT showed that it acted on multiple targets such as MAPK signaling pathways which closely related to metabolic disorders. Most upregulated genes in the NOBT group were closely related to glucose and lipid metabolism genes such as ANAPC5, which could be used as markers to monitor responses to the NOBT group. Application of MAS-the CapitalBio analysis system in-depth analysis of the experimental results showed that the gene was closely associated with the inflammation process was the the CD86the THBS1core network system, the abnormal activation of both closely associated with metabolic disorders.4. QGP verifrcanon of Gene array data:14genes in NOBT group (ANAPC5、NFKB2、CD86. TNFRSF8-TAOK1、HPRT1、THBS1、CCL5、 GAPDH、ICAM1、WASF2、IKBKB、SOCS3、)associated with inflammation process signaling pathways were chosen to verify the Gene array experiments were upregulated. NFKBIZ was down-regulated in the NOBT group. The changes, observed with this technique confumed results obtained by the Gene array, although the variations in magnitude of the changes between the two technologies were observed.
Keywords/Search Tags:Phlegmy-wet constitution, inflammatory, cytokines, SignalTransduction, Etiology and Pathogenesis
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