| Objective:In this study,rat hepatocellular carcinoma was induced by using DEN inducer,and small molecule metabolic markers and their involved metabolic pathways in rat body fluids and organs were detected by nuclear magnetic resonance(1H-NMR).Methods : Twenty-one healthy male SD rats were randomly divided into normal group and hepatocellular carcinoma group.After the establishment of the rat model,24 hours of fasting can not help the water to collect urine,then weighed,taken plasma,kidney,liver,brain,spleen,heart and other tissues,nuclear magnetic resonance1H-NMR detection,and the use of orthogonal partial minimum two Multivariate discriminant analysis(OPLS-DA)and multivariate statistical methods were used to analyze the changes of metabolic profile in each group of rats.Results: According to the results of body weight,the weight of SD rats at different time(week)in each group had significant difference(P<0.001).It could be seen that there were significant differences in the weight of heart,liver and spleen between normal control group and hepatocellular carcinoma model group(p < 0.01).According to the results of organ index comparison,there were significant differences between brain and kidney,liver and spleen tissues and healthy control group.According to the results of OPLS,the metabolic pathways with different changes in body fluid(urine and plasma)were valine,leucine and isoleucine biosynthesis(leucine and isoleucine);glycine,serine and threonine metabolism(choline,glycine,creatine,pyruvate);pyruvate metabolism(lactic acid,pyruvate,acetic acid);alanine,aspartic acid and alanine.Glutamic acid metabolism(alanine,pyruvic acid,glutamine);glycolysis or gluconeogenesis(lactic acid,pyruvic acid,acetic acid);butyric acid metabolism(pyruvic acid,acetoacetic acid,succinic acid);TCA cycle:(pyruvic acid,citric acid,succinic acid);glyoxylic acid and dicarboxylic acid metabolism(citric acid,formic acid);Valine is the metabolic pathway of differential changes in rat viscera.Biosynthesis of leucine and isoleucine(leucine,isoleucine);metabolism of glycine,serine and threonine(choline,glycine,creatine,pyruvate)pyruvate(lactic acid,pyruvate,acetic acid);metabolism of alanine,aspartic acid and glutamic acid(alanine,alanine,glutamine)glycolysis or glycoisogenic(lactic acid,pyruvate acid,acetic acid)Hemi Metabolism of cystine and methionine(methylpyrimidine,pyruvic acid);pyruvate metabolism(lactic acid,pyruvic acid,acetic acid);arginine and proline metabolism(L-proline,creatine,L-glutamic acid);starch and sucrose metabolism(alpha-glucose,beta-glucose)Conclusion:The hepatocellular carcinoma model was established by using DEN inducer.The body fluids and organs of rats were detected and analyzed by metabonomics.The occurrence and development of hepatocellular carcinoma was accompanied by changes of small molecular markers in vivo through differential metabolites and metabolic pathways.The occurrence status of the disease was determined by differential changes of small molecular organisms,and the small molecular organisms in body fluids and organs were determined by differential changes of small molecular organisms,the difference shows that there is a significant difference in pyruvate content in body fluid and organs of DEN carcinogenic group,The change of pyruvate content decreases the energy metabolism of glycolysis source,and the body is in a state of energy deficiency.Alanine is an important intermediate regulator of glucose metabolism.The content of alanine in body fluids and organs also has significant changes.After drinking diethylnitrosamine solution for a long time,it will produce toxicity to various organs in the body,resulting in disorder of amino acid metabolism and significant changes in the corresponding metabolite content.According to the experimental results,diethylnitrosamine is not only toxic to the liver,but also toxic to brain,spleen,heart and kidney tissues in vivo,causing corresponding changes of metabolites in the organs,resulting in energy metabolism disorders,amino acid metabolism disorders and other changes in the body system. |
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