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Effect Of Resveratrol On Central Metabolic Pathways In Rat

Posted on:2017-05-10Degree:MasterType:Thesis
Country:ChinaCandidate:H S WangFull Text:PDF
GTID:2284330485454528Subject:Fermentation engineering
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In recent years, resveratrol got a lot of research in longevity and against modern civilization disease. Its main mechanism is activation of SIRT gene(directly or exerts its effects on SIRT1 through activation of AMPK), to future regulate the various physiological functions of the body’s. However, prolong life, metabolic disorder disease, AMPK and SIRT genes, their pathogenesis, mechanism or functional mechanism is directly associated with the body’s metabolism. So, the effect of resveratrol on the body’s metabolism to be understanding, we can get the effects and mechanisms of resveratrol on body more scientific and accurate. Now, there is a lot of reports about resveratrol in the word, most of them were focused on the pathology, and reports of its direct impact on the metabolic situation is relatively less. There is no research on the metabolic network in the whole body as the research object, especially.Therefore, in there paper, based on blood circulation system, with "directed weighted" lactate metabolism network as the research theory and methods. Adopting 8 to 10 weeks of male SD rats as the research object, set the blank group, and low(3 mg/kg), medium(10mg/kg), high(30 mg/kg) three resveratrol treatment group, 18 replicate of each treatment.After five days of adaptation, at 12 o ’clock gavaged, after gavage, at 14.5, 15 and 15..5 o’clock took blood, for metabolic network flux analysis and 13 enzymes expression level involved in the metabolic pathway measurement and research.Results: the low and medium treatments of resveratrol showed a significant decrease on the level of catabolism and increase on anabolism, and low dose group is most significant.It is more beneficial to prolong life and fight against metabolic disorder in the low dose.High dose group showed catabolism increased as a result, the doses may not have useful function, and even speculated that, due to excessive gastric dose of resveratrol could enhance the body’s immune surveillance and induced effect, making the body produce inflammatory state, thus by enhancing immunity and catabolism in response to injury,which is under high dose the toxic effects of resveratrol may present. In general, less resveratrol may be more beneficial. Metabolic reaction is catalyzed by enzymes, so, we also determined enzyme involved in the network of central metabolic pathways. The aspect of expression level of 13 enzymes, compared with blank group, low dose group showed a significant decrease in PFK(p < 0.05), GAPDH(p < 0.05), PDHC(p < 0.05), andα-KGPDH(p < 0.01); Significant increase of enzyme has IDH(p < 0.01), and MDH(p <0.01). In middle dose group, significantly lower enzyme have IDH(p < 0.01); Significant increase of enzyme has MDH(p < 0.01). In the high dose group, significantly lower enzyme with ALD(p < 0.05), and IDH(p < 0.01); Significant increase of enzyme has HK(p < 0.01), G6PDH(p < 0.01), PDHC(p < 0.01), and α-KGPDH(p < 0.01).Metabolic reactions(metabolic flux) is regulated by enzyme, they(metabolic reaction and enzyme) constitute the metabolic network as a whole, and the overall metabolic network control by what? Between the food and the body not only has the material and energy flow,and information flow. Research shows that the functional food is through exchange of information between the body to play a role. Functional food in the gut interact with the corresponding receptors, further influence between intestinal cells, and exchange of information between other cells of the body(the signal passed by cytokines), regulating the body’s immune, and ultimately role in metabolism. It is a signal transduction process of causal logic relationship. Based on this, we take enzymes and cytokines that significant changes(cytokines by others within the team and finish with the experiment) to Pearson correlation analysis to find the relationship between networks of metabolism and cytokines,further explore how food regulate metabolism by cytokines networks. The results show that the low dose group, EGF(-0.997), IL- 17 a(0.988), they correlation coefficient with 13 enzymes are in the range of 1 to 1; Medium dose group, IL- 12 p70(0.955) and Eotaxin(0.988) they correlation coefficient are within the range 1 to 1; High dose group, MIP 1alpha(0.998), IL- 18(0.92), MCP- 1(0.992) and VEGF(0.982) and Fractalkine(-0.993),they correlation coefficient are in the range of 1 to 1. Correlation value is positive(negative)illustrate the cytokine changes and expression of enzyme to a change in the quantity of positive(negative), namely if the levels of cytokines is increase(decrease), the expression of the enzyme quantity will increase(decrease). That is to say, after gavage different doses resveratrol, by changing the synthesis and secretion of cytokines to further adjust(correlation coefficient value is positive, positive adjust, correlation coefficient value is negative, negative adjust) expression level of enzyme in the central metabolic pathways,and to regulate the metabolic network. Which further confirmed the functional foods’ signal pathway in the body.This method(including cytokines, metabolic network as well as the combination between the two) for food and functional food physiological functional(immune,metabolism level and signal transmission way) evaluation provides a set of more scientific research method and theory.
Keywords/Search Tags:Resversatrol, Circulatory system, Lactate, Flux analysis, enzymes expression level, immunmetabolism
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