| 초록 |
Background: AKI is a common complication in critically ill hospitalized patients. Many reports have demonstrated the relevance of interactions between the kidney and distant organs. Metabolomics could provide quantitative measurements. Understanding the metabolic thru which AKI affects distant organ function is critical to the refinement of therapies to prevent or attenuate AKI-associated morbidity and mortality. Here in we aim to evaluate the affect IR AKI alters the metabolomics profiles in distant organs.
Methods: We subjected mice to IR AKI (22 min of renal pedicle clamping and then reperfusion) and measured serial changes of metabolite profiles in the sera, heart, lungs, and liver 4 hours, 24 hours and 7 days after injury. Ultra performance liquid chromatography – tandem mass spectrometer runs for metabolic profile of these organs.
Results: 1) Energy metabolism in plasma, heart, liver and lung after renal ischemia/reperfusion: Plasma: At 24 hours, energy metabolites changes peak. Plasma accumulation of glucose-6-phosphate was observed at 24 hours after reperfusion, but glucose, pyruvate, lactate decreased. Heart: Glucose and glucose metabolites accumulated at 24 hours. The increased glucose and glycolysis were observed.Liver: At 24 hours, most glucose and glycolysis metabolites decreased. TCA metabolites decreased. Lung: Lung energy metabolites were mildly altered at all time points. 2) Amino acids: proteolysis, transamination, and glutathione homeostatsis :Plasma: At 4 hours, asparagine, aspartate, histidine, and cysteine increased. At 24 hours, most amino acid decreased. Decreases of GSH and GSSG and 5-oxoproline were observed at 24 hours. Heart: Alanine and aspartate in heart persistently decreased. Also glutamate decreased at 4 and 24 hours. Decreases of GSH and GSSG were observed at 24 hours. Liver: Liver amino acids did not change at 4 hours. At 24 hours, some amino acids decreased. Among these, glutamine, glutamate, and GSH decreased. Lung: Some amino acids in lung decreased at 4 and 24h, and recover at 7 d. GSH decreased at 4 and 24h. GSSG decreased at 4h.
Conclusion: Reactive oxygen species might be involved in distant organ damage. IR AKI produced dynamic changes of energy metabolites, which is peaked at 24 hours. Glucose and glucose metabolites accumulated in heart but did not accumulate in the liver. Anaplerosis is a key feature in heart, while cataplerosis is demonstrated in the liver following IR AKI. |