Mechanism Of Hyperoxic Acute Lung Injury In Neonatal Rats Based On Multi-omics And The Mechanisam Of Neuropeptide Substance P Intervention

PART ?MECHANISM EXPLORATION OF HYPEROXIC ACUTE LUNG INJURY IN NEONATAL RATS BASED ON MUTI-OMICSObjective: This part aims to explore the potential core pathways and biomarkers of hyperoxic acute lung injury based on metabolomics and proteomics,via the development of neonate Sprague-Dawley(SD)rats,hyperoxic acute lung injury animal models.Methods: The animal model of neonate SD rats was developed and divided into atmosphere group and hyperoxia group.The lung tissue was detected after executing the animals,and then IL-6,IL-1?,TNF-?,GSH,MDA levels and SOD activity were detected.Subsequently,the tissue samples were detected via UPLC-MS for metabolomics,i TRAQ for non-targeted proteomics and PRM targeted proteomics.Then bioinformatics analysis was performed.Results: Compared with atmosphere group rats,the observations of pathology in hyperoxia group included hemorrhage of pulmonary alveoli,with percolates,with thickened mesenchyme and huge inflammatory cell infiltration.ELISA revealed that IL-6,IL-1?,TNF-? and MDA levels were significantly increased in hyperoxia group while SOD activity and GSH levels significantly decreased.By metabolomics,we found the metabolites in hyperoxia induced neonate SD rats lung tissue were significantly changed,involved six potential metabolic pathways,ABC transporters,biosynthesis of unsaturated fatty acids,arachidonic and metabolism,taurine and hypotaurine metabolism,retinol metabolism and linoleic and metabolism.Multiple logistics analysis and ROC curve analysis indicated that Eicosapentaenoicacid was a potential biomarker.By proteomics analysis,we found 247 DEPs,with 117 up-regulated and130 down-regulated,the biological status included stress response,regulation for response to injury,the molecular function included oxygen transport,anti-oxidation function,protein binding and peptide enzyme regulation,etc.The involved pathways included oxidative phosphorylation,complement pathways,lipids metabolism and Glutathione metabolism.NADH dehydrogenase complex I-? subunit 2was a potential biomarker.Conclusion: This part observed significant change for hyperoxia induced lung injury.Several pathways were found via metabolomics and proteomics.Eicosapentaenoicacid and NADH dehydrogenase complex I-? subunit 2 were potential biomarkers.PART ? EXPLORABLE EXPERIMENTAL STUDY FOR TREATMENT OF NEUROPEPTIDE SUBSTANCE P ON HYPEROXIC ACUTE LUNG INJURY IN RATSObjective: This part is continuous study of our research group,in order to elucidate the potential mechanism of substance P in treating acute lung injury via metabolomics and proteomics.Methods: Another group of substance P group was added,in consistency with the other two groups.The ratss in SP group received peritoneal injection of SP600125 30mg/kg.Other model development,pathology analysis,ELISA,metabolomics and proteomics were descripted as before.Results: Hub pathways included biological synthesis of unsaturated fatty acid,metabolites pathways,thiamine pathways,biological synthesis of pantothenic acid and CoA,biological synthesis of amide-tRNA,?-alanine metabolism,purine metabolism and melanin synthesis.Twenty-three differential proteins were found,with seven up-regulated and sixteen down-regulated.By PRM protein validation,carbonic anhydrase ?,the hub differential protein was detected.Further literature analysis found that carbonic anhydrase I-thiamine is potential metabolic pathway for SP in treating acute lung injury.Conclusion: Carbonic anhydrase ?-thiamine is potential metabolic pathway for SP in treating acute lung injury.