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Metabolomics Analysis Of Acute Ischemia/Reperfusion Injury In Rat Kidneys

Posted on:2009-05-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:C C JiFull Text:PDF
GTID:1114360245977401Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective:To evalute the feasibility of metabolomic technology for developing a rapid and early screen for acute kidney injury,to explore the pathogenessis of AKI and search for new biomarkers and therapy target.Methods: The model of IRI involved bilateral renal artery occlusion for 45 min in male SD rats. Blood samples were taken before the operation or on different time point after reperfusion.24-hour urine samples were colleted on Day 1,2,3 and 4 HPLC-MS-based metabonomic analysis was used to investigate serum and urinary metabolites of the rats.Data were proceeded and subjected to principle component analysis(PCA) and Partial Least Squares-Discriminanl analysis(PLS-DA),then yielded score plots and loading plots,which gave the information about classify and differential metabolites.These differential metabolites were identified by the Metlin database.As the levels of carnitine and its derivatives were decreased in I/R injurt rats according to the primary results,we investigated whether L-carnitine could protect rat kidney from ischemia/reperfusion injury and the mechanism were explored.Results: Changes in the pattern of endogenous metabolites as a result of ischemia/reperfusion injury of rat kidneys were readily detected as early as 2 hours after reperfusion,when was earlier than the increase of BUN and serum creatinine,which were upregulated at 4 hours after reperfusion.The most two kinds of differential metabolites were phosphatidylcholines and carnitines,the former were upregulated and the latter were downregulated.This may indicated that carnitine wre more consumpted in ischemia reperfusion injury.We investigated whether L-camitine could protect rat kidney from ischemia/reperfusion injury.We found that preventive or delayed(just after reperfusion) administration of L-carnitine could abrogate the injury induced by ischemia/reperfusion in rat kidneys,which may be associated with the downregulation of mitochondria membrane permeability by L-carnitine.
Keywords/Search Tags:acute kidney injury, metabolomics, L-carnitine, apotosis, mitonchondria membrane permeability
PDF Full Text Request
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