Selection Of Metabolic Biomarkers From Rat Urine Applied In The Early Stage Of Acute Ionizing Radiation Damage

With the rampancy of a global terrorist activities including nuclear terrorismis, frequency of nuclear accidents in the process of peaceful use of nuclear energy and wide application of radioactive source in the medicine, the potential risk of radiation damage from ordinary people increases significantly, and a a large-scale radiological incident may occur at any time. The biomarkers in the early stage of acute ionizing radiation for the rapid radiation triage are important for the rapid radiation triage, rational usage of limited medical resources and scientific treatment strategy. In this research, Wistar rats were the research object, the acute radiation damage biomarkers in the urine are selected by gas chromatography-mass spectrometry(GC-MS) and amino acid target analysis based on liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) techniques. Moreover, the metabolic pathways involved in the radiation damage were explored.1. The untargeted metabolomic method based on the GC-MS in the urine samples from rats was established. The urine samples pretreatment methods and the analytical conditions of gas chromatography and mass spectrometry were optimized. Then, the repeat of sample pretreatment methods, the inter-day precision and intra-day precision were also represented. Finally, the urine metabolites were identified by automated mass spectral deconrolution and identification system(AMDIS) and retention index.2. The changes of metabolites levels from urine samples were investigated using the untargeted metabolomic method based on the GC-MS and amino acid target analysis method based on liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Genetic algorithm(GA) and multiple stepwise linear regression(MLSR) were both used to selected the radiation damage characteristic differences metabolites. For the convenience of clinical application, the best panel of potential radiation damage biomarkers was screened through multiple means and then was applied to the separation of different doses groups and early radiation damage triage.3. The topology networks among radiation damage characteristic metabolites were contrasted by the pearson correlation analysis in order to explor the relevant relationships. The metabolic pathway analysis showed aminoacy-t RNA biosynthesis, citric acid cycle, amino acids metabolism and urea cycle were involved in radiation damage. The results provided the experimental evidence for the acute ionizing radiation damage and repair mechanisms.