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1、Early biomarkers for diagnosis of postoperative acute renal failure 早期生物標記診斷術後急性腎臟衰竭,楊 光 華,Devarajan P(2005)Curr Opin Pediatr,Metabolic consequences of acute IRI to kidney tubule cells,SensitivitySpeedSimple workflowComprehensive profiles High multi-plexity,The characteristic of biomarker,Goal,Devel
2、op suitable monitoring system via biomarkers from NTUH SICU ARF databank.Identify the role of AKI biomarkers among injury,protection or repair.,The animal model of ischemia-reperfusion injury for AKI,40 min,3,6,12,24,48,(hr),0,Sham,The serum creatinine from post-operative rats,Serum creatinine measu
3、rements obtained at various time points post-cardiac surgery from NSARF databank,Urine netrin-1 from 9 AKI patients in NSARF databank,Netrin-1 in urine collected from 1-2:normal health volunteers,3-10:postoperative patients without acute kidney injury(AKI),11-13:postoperative patients with AKI.40 mg
4、 creatinine for each human sample was subjected to Western blot analysis of Anti-netrin-1 Ab.,Neogenin:One receptor,many functions,Nicole and Brian(2007)The international journal of biochemistry&cell biology,RGMc=Hemojuvelin(HJV),Hemochromatosis type 2(HFE2),Ivana DD et al.,(2007)JCI,Transcriptional
5、 regulation of hepcidin by the BMP/Smad pathway,The up-regulation of hepcidin in these segments of the nephron after renal ischemia leads to a down-regulation of the ferroportin exporter,preventing the further release of free iron into tissues and resulting perpetuation of tubular injury.,Modified f
6、rom Douglas BK(2009)BMC Medical Genomics,Overview of the roles of hepcidin and NGAL after IRI,Time course of Netrin-1,HJV,co-receptor Neogenin and Pendrin protein expression in rat kidney after I/R injury,MW:85.73 kDa,Pendrin,is an ion exchanger found in the cortical collecting duct,thyroid gland an
7、d inner ear.An apical Cl-/HCO3-exchanger,mediates chloride reabsorption in the connecting tubule and the cortical collecting duct and therefore is involved in extracellular fluid volume regulation.,Sham 3 6 12-112-2 24-124-2 48-1 48-2(hr),WB:Urinary HJV,15%SDS-PAGECBR staining,Urinary HJV from rat a
8、fter IR-Injury,After IRI,Urinary HJV after 24 hr post-operation from NSARF databank,林 楊 潘 趙 劉,HJV,WB:1st Anti-HJV pAb15%SDS-PAGE,Conclusion,Urinary netrin-1 is an early diagnostic biomarker of AKI in post-cardiac surgery patients.Hemojuvelin may be a potential biomarker involved in iron homeostasis after IRI.,
