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Metabolism Studies Of Serum Urine Based On NMR Technology Of Coke Oven Workers And Benzo(a) Pyrene Exposure In Rats

Posted on:2016-11-06Degree:MasterType:Thesis
Country:ChinaCandidate:Y F ZhiFull Text:PDF
GTID:2284330479992526Subject:Public health
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Objective:By 1H-NMR metabolomics serum, urine of coking plant workers and B(a)P infected rat, combined with animal pathology biopsy, serum biochemistry, urine routine of workers and infected rats. Explore the B(a)P and long-term exposure to B(a)P poison effect characteristics of coke oven workers, and find the early damage of metabolic marker, in order to provide new ideas of further reduce the coke oven workers occupational hazards of occupational Exposure.Method:Coking plant workers survey by age, smoking, drinking, working age, BMI pairing methodology. Chosen 40 coke oven workers(roof workers, furnace workers side) as the exposed group, as well as non-focus within 40 plant furnace exposed workers(administrative staff, security) as a control group.Collect morning urine and blood of workers, using high-performance liquid chromatography operating detect B(a)P concentrations and worker urine 1-hydroxy-pyrene in urine.Select 24 healthy male SD rats, weighing about 120-140 g, were randomly divided into four groups,(each 6). Including control group, respectively(olive oil), low-dose group(1mg/kg), the dose(2.5mg/kg), high dose group(6.25mg/kg); Exposure group by intraperitoneal injection B(a)P. Control group injected olive oil. Exposed three weeks,After 24 h urine collection, the rats were anesthetized, the abdominal aorta blood samples,anatomical heart, liver, spleen, lung and kidney.Detection of coking plant workers and B(a)P infected rats serum biochemistry, serum and urine routine urine; Using the 1H-NMR techniques to detect serum, urine metabonomics. Mest Re Nova, SMICA P+11 and SPSS19.0 software to deal with the experimental results analysis.Result:1 Based on NMR coke oven workers serum, urine metabonomics research results.Concentration of benzene and B(a)P in the working environment of coke oven area is significantly higher than the coke oven area, the difference was statistically significant(P<0.05).The object of study 1-hydroxy pyrene exposure levels in urine concentration control group < exposure group, the difference was statistically significant(P<0.05).The serum biochemical indicators results showed that the coke oven workers(exposed group) in cereal third ALT, CHOL, HDL, LDL were higher than control group in the corresponding indicators, and the difference was statistically significant(P<0.05).And its various indexes were in normal range.Coking plant workers routine urine indicators suggest that urine specific gravity of exposed workers, and urine PH were higher than the control group and the difference has statistical significance(P<0.05), and its value in the normal range.11H-NMR analysis showed that serum screening of exposure group and control group in the main content includes: the differences between lactic acid, alanine, pyruvic acid,branched chain amino acids(leucine, isoleucine, and valine),lipid, glutamine, glycerin phosphoryl choline, glucose.Including lactic acid, pyruvic,alanine acid increased in exposed group was obviously, glucose, branched chain amino acid, glutamine, glycerin phosphoryl choline was significantly reduced, and the difference was statistically significant(P<0.05).1- hydroxyl urine pyrene was a positive correlation with lactic acid,pyruvic acid, lipoprotein(P<0.05),1-hydroxyl urine pyrene and glutamine and glycerol phospholipid choline negatively correlated(P<0.05).1H-NMR results, analysis of coke oven workers urine metabolites in the exposed group compared with control group in the obvious change, we analyze the urine of differences in metabolic substances are: lactic acid,alanine, dimethylamine, alpha ketone glutaric acid, pyruvic acid, citric acid, betaine,hippuric acid, succinic acid.Exposure group and control group compared with lactic acid,dimethylamine increased significantly, alpha ketone glutaric acid, pyruvic acid,citric acid,hippuric acid decreased obviously,the difference was statistically significant(P<0.05).1-hydroxyl urine pyrene were negatively related with citric acid,betaine(P<0.05).2 Based on NMR B(a)P infected rats serum, urine metabonomics research results.After the canister, each animal is normal, animals of 6.25mg/kg infected group appeared irritability, depression, weight loss,the colour yellow and dry and other symptoms.Pathological sections showed,liver biopsy of 6.25mg/kg group lymphocyte infiltration of portal area, liver cells and fat.2.5mg/kg group was obviously showed liver fat. Lung biopsy showed that alveolar wall edema, thickening, alveolar closure in 6.25mg/kg group,alveolar closed in 2.5mg/kg group of. alveolar wall thickening in 1.25mg/kg group.Renal biopsy showed that bowman’s capsule gap decrease, even disappear in high dose group.6.25mg/kg group compared with control group ALT, AST, TC, TG, CREA, LDH increased significantly(P<0.05).2.5mg/kg group compared with control group, ALT,TG,CREA,LDH increased significantly(P<0.05).Routine urine of rats,6.25mg/kg group compared with control group, the positive rate of urine protein increased.Other indicators between the four groups were no significant difference(P>0.05).Rats serum1H-NMR test results showed that high dose and dose in the evidence difference existed in the metabolic characteristics and the control group, low dose might be relatively limited effects on endogenous metabolites in rats.High dose of VLDL,LDL,alanine, branched chain amino acid, lactic acid, pyruvic acid, glycerin, glucose, glutamine is decreased obviously.N-acetyl glycoprotein.Creatinine and pyruvate in low dose group was obviously higher than that of control group.Analysis of the urine test results showed that high dose and dose on the metabolic characteristics and the control group, there is a difference between low dose overlap with the control group, low dose these metabolites and no obvious change compared with control subjects.6.25mg/kg dose of VLDL,LDL, alanine, branched chain amino acid, lactic acid, pyruvic acid, glycerin, glucose, glutamine is decreased obviously.The glucose in the lower dose group, N-acetyl glycoprotein.Creatinine and pyruvate in 1mg/kg group was obviously higher than control group.Conclusions:B(a)P infected rats and long-term exposure to B(a)P in coke oven workers showed the energy metabolism disorder, tricarboxylic acid cycle.And we found the B(a)P infected with coke oven workers long-term exposure to B(a)P serum, urine metabolic marker system.
Keywords/Search Tags:Benzo(a)pyrene, Metabolomics, Coke oven workers, Energy metabolism, Citric acid cycle
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