Experimental And Clinical Study On Metabolic Fingerprint Drawing, Metabolites Screening And Nutritional Therapy Optimization In Severe Burn

Background:Persistent and irreversible hypermetabolic response is the main metaboliccharacteristics in severe burned patients. After burn injury, the primary pathologicalphenomena are energy consumption and catabolism increased significantly, and nutrientsutilize barriers. Current clinical nutritional therapy not fully consider the tolerance degree ofnutrition in severe burned patients. A lot of exogenous nutrients can not be utilized well,and may aggravate metabolic disorder. The result is the autophagy metabolism, continuousconsumption, and progressive emaciation continuity. Now the major obstacle in burnnutrition therapy is the understanding of metabolic change characteristics postburn notdeep enough. The pertinence and effectiveness of nutrition therapy remains to be furtherimproved. An accurate knowledge of metabolic pattern change characteristics postburnis a prerequisite for rational nutrition therapy. The current testing methods can not meetrapid access to complete metabolic information. Metabolomics provide an effective tool forcomprehensive and systematic understanding of metabolic pattern changes after burn injury.Objective:To establish plasma metabolomics fingerprint spectrum in severe burn patients using1H-NMR spectroscopy. To understand the basic rules of severe burn metabolism, throughdata mining, data modeling and pattern recognition analysis to screen a set of biomarkersthat could be used for prognostic prediction in severe burned patients，and establish adiscriminant formula for predicting prognosis. Using the advantages of metabonomics tojudge the rationality of the new nutritional therapy protocol by severe burned rats model,and optimize current burn nutritional therapy.Methods:1. Establish a plasma metabolomics fingerprint spectrum in severe burned patients.According to including and excluding standard, twenty-one severe burned patients and tenhealthy control individuals were enrolled in this study. The plasma samples from patients and healthy individuals were collected for NMR measurements. The NMR spectra data waspattern recognized by using principal component analysis and partial least squares fordrawing burn patients metabolomics fingerprint.2. Base on establishing severe burn patients metabolic fingerprint, further mining andanalyze the data of different disease course, damage degree, and clinical prognosis.Screening metabolic markers and establish death prediction formula for judging prognosisthrough The Human Metabolome Database.3. The effects of different energy supplement, variety of nutrients ratio and glutamineadminstration on metabolism and prognosis were observed and the best nutritional supportscheme was screened by using metabonomics analysis technology and resting energyexpenditure (REE), blood glucose, glucose tolerance, bacterial quantitative detectionmethods on burned rats model.Results1. Successfully established the severe burn patients metabolic fingerprint. Theresults showed that the metabolic patterns were significant difference among burnedpatients, healthy individuals, burn shock stage and burn other stage, as well as death andsurvival patients.2. Using metabolomics techniques, we found an eigen-metabolome that consists of12metabolites to distinguish burned patients and healthy individuals, and15metabolites todifferentiate burn shock stage and other stage, as well as25metabolites to identify deathand survival patients.3. Analyze the data of different outcomes by metabolomics techniques, establishedmetabonomics formula for predicting death in severe burned patients: Y=-1.1568x-5.4133.4. NMR spectra of the plasma samples showed that there were significant differenceamong different dose of nutrition support, different nutrients ratio and glutamine treatment.5. Animal experimental results showed that the best nutritional support scheme wasenergy supplement should reach75%REE in the first week after burn, and reach100%REEin the second week. The best proportion of sugar, fat and protein was70%：10%：20%.More over, enteral nutrition with glutamine administration was beneficial to body recoveryafter burn injury. Conclusion1. Metabolomics techniques based on NMR can be used to monitor metabolism insevere burn patients. The integrated1H-NMR metabolome and metabolic network analysisis useful for visualizing complex metabolic disturbances after severe burn injury and mayprovide a new quantitative injury severity evaluation for future clinical use.2. NMR spectra of the plasma samples showed significant differences between burnedpatients and healthy individuals, burn shock stage and other stage. Using metabolomicresearch methods find some metabolic markers for predicting death.3. Successfully established prognostic prediction formula in severe burned patients:Y=-1.1568x-5.4133.4. Create the best nutritional support scheme base on burn rat model: energysupplement should reach75%REE in the first week after burn, and reach100%REE in thesecond week, and the best proportion of sugar, fat and protein was70%：10%：20%. Moreover, give early enteral nutrition supplemented with glutamine as soon as possible.