Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/14484
標題: 犬泌尿道疾病尿中NGAL之分子型態與濃度變化
Concentration and forms of urine neutrophil gelatinase-associated lipocalin (NGAL) in dogs with urinary diseases
作者: 邱曉娸
Chiou, Hsiao-Chi
關鍵字: 犬;Concentration;泌尿道疾病;NGAL;分子型態;濃度;forms;urine neutrophil gelatinase-associated lipocalin;NGAL;dogs;urinary diseases
出版社: 獸醫學系暨研究所
引用: 1. Aghel A, Shrestha K, Mullens W, Borowski A, and Tang WH. Serum neutrophil gelatinase-associated lipocalin (NGAL) in predicting worsening renal function in acute decompensated heart failure. Journal of cardiac failure 16: 49-54, 2010. 2. Aigner F, Maier HT, Schwelberger HG, Wallnofer EA, Amberger A, Obrist P, Berger T, Mak TW, Maglione M, Margreiter R, Schneeberger S, and Troppmair J. Lipocalin-2 regulates the inflammatory response during ischemia and reperfusion of the transplanted heart. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 7: 779-788, 2007. 3. Alvelos M, Lourenco P, Dias C, Amorim M, Rema J, Leite AB, Guimaraes JT, Almeida P, and Bettencourt P. Prognostic value of neutrophil gelatinase-associated lipocalin in acute heart failure. International journal of cardiology 165: 51-55, 2013. 4. Andre E, Stoeger T, Takenaka S, Bahnweg M, Ritter B, Karg E, Lentner B, Reinhard C, Schulz H, and Wjst M. Inhalation of ultrafine carbon particles triggers biphasic pro-inflammatory response in the mouse lung. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology 28: 275-285, 2006. 5. Askenazi DJ, Koralkar R, Levitan EB, Goldstein SL, Devarajan P, Khandrika S, Mehta RL, and Ambalavanan N. Baseline values of candidate urine acute kidney injury biomarkers vary by gestational age in premature infants. Pediatric research 70: 302-306, 2011. 6. Aydogdu M, Gursel G, Sancak B, Yeni S, Sari G, Tasyurek S, Turk M, Yuksel S, Senes M, and Ozis TN. The use of plasma and urine neutrophil gelatinase associated lipocalin (NGAL) and Cystatin C in early diagnosis of septic acute kidney injury in critically ill patients. Disease markers 34: 237-246, 2013. 7. Bagshaw SM, Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Oudemans-van Straaten HM, Ronco C, Kellum JA, Beginning, and Ending Supportive Therapy for the Kidney I. Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clinical journal of the American Society of Nephrology : CJASN 2: 431-439, 2007. 8. Bao G, Clifton M, Hoette TM, Mori K, Deng SX, Qiu A, Viltard M, Williams D, Paragas N, Leete T, Kulkarni R, Li X, Lee B, Kalandadze A, Ratner AJ, Pizarro JC, Schmidt-Ott KM, Landry DW, Raymond KN, Strong RK, and Barasch J. Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex. Nature chemical biology 6: 602-609, 2010. 9. Beger HG, and Rau BM. Severe acute pancreatitis: Clinical course and management. World journal of gastroenterology : WJG 13: 5043-5051, 2007. 10. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, and Acute Dialysis Quality Initiative w. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Critical care 8: R204-212, 2004. 11. Bennett M, Dent CL, Ma Q, Dastrala S, Grenier F, Workman R, Syed H, Ali S, Barasch J, and Devarajan P. Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a prospective study. Clinical journal of the American Society of Nephrology : CJASN 3: 665-673, 2008. 12. Berger T, Togawa A, Duncan GS, Elia AJ, You-Ten A, Wakeham A, Fong HE, Cheung CC, and Mak TW. Lipocalin 2-deficient mice exhibit increased sensitivity to Escherichia coli infection but not to ischemia-reperfusion injury. Proceedings of the National Academy of Sciences of the United States of America 103: 1834-1839, 2006. 13. Bock JS, and Gottlieb SS. Cardiorenal syndrome: new perspectives. Circulation 121: 2592-2600, 2010. 14. Bolignano D, Basile G, Parisi P, Coppolino G, Nicocia G, and Buemi M. Increased plasma neutrophil gelatinase-associated lipocalin levels predict mortality in elderly patients with chronic heart failure. Rejuvenation research 12: 7-14, 2009. 15. Bolignano D, Coppolino G, Romeo A, De Paola L, Buemi A, Lacquaniti A, Nicocia G, Lombardi L, and Buemi M. Neutrophil gelatinase-associated lipocalin (NGAL) reflects iron status in haemodialysis patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 24: 3398-3403, 2009. 16. Bolignano D, Donato V, Lacquaniti A, Fazio MR, Bono C, Coppolino G, and Buemi M. Neutrophil gelatinase-associated lipocalin (NGAL) in human neoplasias: a new protein enters the scene. Cancer letters 288: 10-16, 2010. 17. Bolignano D, Lacquaniti A, Coppolino G, Donato V, Campo S, Fazio MR, Nicocia G, and Buemi M. Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clinical journal of the American Society of Nephrology : CJASN 4: 337-344, 2009. 18. Brun-Buisson C. The epidemiology of the systemic inflammatory response. Intensive care medicine 26 Suppl 1: S64-74, 2000. 19. Cai L, Borowiec J, Xu S, Han W, and Venge P. Assays of urine levels of HNL/NGAL in patients undergoing cardiac surgery and the impact of antibody configuration on their clinical performances. Clinica chimica acta; international journal of clinical chemistry 403: 121-125, 2009. 20. Cai L, Rubin J, Han W, Venge P, and Xu S. The origin of multiple molecular forms in urine of HNL/NGAL. Clinical journal of the American Society of Nephrology : CJASN 5: 2229-2235, 2010. 21. Carroll JK, Herrick B, Gipson T, and Lee SP. Acute pancreatitis: diagnosis, prognosis, and treatment. American family physician 75: 1513-1520, 2007. 22. Chakraborty S, Kaur S, Muddana V, Sharma N, Wittel UA, Papachristou GI, Whitcomb D, Brand RE, and Batra SK. Elevated serum neutrophil gelatinase-associated lipocalin is an early predictor of severity and outcome in acute pancreatitis. The American journal of gastroenterology 105: 2050-2059, 2010. 23. Cho H, and Kim JH. Lipocalin2 expressions correlate significantly with tumor differentiation in epithelial ovarian cancer. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 57: 513-521, 2009. 24. Cowie MR, Komajda M, Murray-Thomas T, Underwood J, Ticho B, and Investigators P. Prevalence and impact of worsening renal function in patients hospitalized with decompensated heart failure: results of the prospective outcomes study in heart failure (POSH). European heart journal 27: 1216-1222, 2006. 25. Cowland JB, and Borregaard N. Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans. Genomics 45: 17-23, 1997. 26. Cruz DN, de Geus HR, and Bagshaw SM. Biomarker strategies to predict need for renal replacement therapy in acute kidney injury. Seminars in dialysis 24: 124-131, 2011. 27. Damman K, Masson S, Hillege HL, Maggioni AP, Voors AA, Opasich C, van Veldhuisen DJ, Montagna L, Cosmi F, Tognoni G, Tavazzi L, and Latini R. Clinical outcome of renal tubular damage in chronic heart failure. European heart journal 32: 2705-2712, 2011. 28. Damman K, Voors AA, Hillege HL, Navis G, Lechat P, van Veldhuisen DJ, Dargie HJ, Investigators C-, and Committees. Congestion in chronic systolic heart failure is related to renal dysfunction and increased mortality. European journal of heart failure 12: 974-982, 2010. 29. Devireddy LR, Gazin C, Zhu X, and Green MR. A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake. Cell 123: 1293-1305, 2005. 30. Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Stromberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K, and Guidelines ESCCfP. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). European journal of heart failure 10: 933-989, 2008. 31. Fadel FI, Abdel Rahman AM, Mohamed MF, Habib SA, Ibrahim MH, Sleem ZS, Bazaraa HM, and Soliman MM. Plasma neutrophil gelatinase-associated lipocalin as an early biomarker for prediction of acute kidney injury after cardio-pulmonary bypass in pediatric cardiac surgery. Archives of medical science : AMS 8: 250-255, 2012. 32. Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, and Aderem A. Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron. Nature 432: 917-921, 2004. 33. Friedl A, Stoesz SP, Buckley P, and Gould MN. Neutrophil gelatinase-associated lipocalin in normal and neoplastic human tissues. Cell type-specific pattern of expression. The Histochemical journal 31: 433-441, 1999. 34. Gheorghiade M, Zannad F, Sopko G, Klein L, Pina IL, Konstam MA, Massie BM, Roland E, Targum S, Collins SP, Filippatos G, Tavazzi L, and International Working Group on Acute Heart Failure S. Acute heart failure syndromes: current state and framework for future research. Circulation 112: 3958-3968, 2005. 35. Goetz DH, Willie ST, Armen RS, Bratt T, Borregaard N, and Strong RK. Ligand preference inferred from the structure of neutrophil gelatinase associated lipocalin. Biochemistry 39: 1935-1941, 2000. 36. Grauer GF. Early detection of renal damage and disease in dogs and cats. The Veterinary clinics of North America Small animal practice 35: 581-596, 2005. 37. Grenier FC, Ali S, Syed H, Workman R, Martens F, Liao M, Wang Y, and Wong PY. Evaluation of the ARCHITECT urine NGAL assay: assay performance, specimen handling requirements and biological variability. Clinical biochemistry 43: 615-620, 2010. 38. Hatipoglu S, Sevketoglu E, Gedikbasi A, Yilmaz A, Kiyak A, Mulazimoglu M, Aydogan G, and Ozpacaci T. Urinary MMP-9/NGAL complex in children with acute cystitis. Pediatric nephrology 26: 1263-1268, 2011. 39. Hillege HL, Nitsch D, Pfeffer MA, Swedberg K, McMurray JJ, Yusuf S, Granger CB, Michelson EL, Ostergren J, Cornel JH, de Zeeuw D, Pocock S, van Veldhuisen DJ, Candesartan in Heart Failure: Assessment of Reduction in M, and Morbidity I. Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation 113: 671-678, 2006. 40. Hillege HL, van Gilst WH, van Veldhuisen DJ, Navis G, Grobbee DE, de Graeff PA, de Zeeuw D, and Trial CR. Accelerated decline and prognostic impact of renal function after myocardial infarction and the benefits of ACE inhibition: the CATS randomized trial. European heart journal 24: 412-420, 2003. 41. Hinze CH, Suzuki M, Klein-Gitelman M, Passo MH, Olson J, Singer NG, Haines KA, Onel K, O''Neil K, Silverman ED, Tucker L, Ying J, Devarajan P, and Brunner HI. Neutrophil gelatinase-associated lipocalin is a predictor of the course of global and renal childhood-onset systemic lupus erythematosus disease activity. Arthritis and rheumatism 60: 2772-2781, 2009. 42. Holmes MA, Paulsene W, Jide X, Ratledge C, and Strong RK. Siderocalin (Lcn 2) also binds carboxymycobactins, potentially defending against mycobacterial infections through iron sequestration. Structure 13: 29-41, 2005. 43. Hraba-Renevey S, Turler H, Kress M, Salomon C, and Weil R. SV40-induced expression of mouse gene 24p3 involves a post-transcriptional mechanism. Oncogene 4: 601-608, 1989. 44. Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldman AM, Francis GS, Ganiats TG, Goldstein S, Gregoratos G, Jessup ML, Noble RJ, Packer M, Silver MA, Stevenson LW, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Gregoratos G, Jacobs AK, Hiratzka LF, Russell RO, Smith SC, Jr., American College of Cardiology/American Heart Association Task Force on Practice G, International Society for H, Lung T, and Heart Failure Society of A. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the International Society for Heart and Lung Transplantation; Endorsed by the Heart Failure Society of America. Circulation 104: 2996-3007, 2001. 45. Ichino M, Kuroyanagi Y, Kusaka M, Mori T, Ishikawa K, Shiroki R, Kurahashi H, and Hoshinaga K. Increased urinary neutrophil gelatinase associated lipocalin levels in a rat model of upper urinary tract infection. The Journal of urology 181: 2326-2331, 2009. 46. Kjeldsen L, Bainton DF, Sengelov H, and Borregaard N. Structural and functional heterogeneity among peroxidase-negative granules in human neutrophils: identification of a distinct gelatinase-containing granule subset by combined immunocytochemistry and subcellular fractionation. Blood 82: 3183-3191, 1993. 47. Krumholz HM, Chen YT, Vaccarino V, Wang Y, Radford MJ, Bradford WD, and Horwitz RI. Correlates and impact on outcomes of worsening renal function in patients > or =65 years of age with heart failure. The American journal of cardiology 85: 1110-1113, 2000. 48. Kubben FJ, Sier CF, Hawinkels LJ, Tschesche H, van Duijn W, Zuidwijk K, van der Reijden JJ, Hanemaaijer R, Griffioen G, Lamers CB, and Verspaget HW. Clinical evidence for a protective role of lipocalin-2 against MMP-9 autodegradation and the impact for gastric cancer. European journal of cancer 43: 1869-1876, 2007. 49. Kumpers P, Hafer C, Lukasz A, Lichtinghagen R, Brand K, Fliser D, Faulhaber-Walter R, and Kielstein JT. Serum neutrophil gelatinase-associated lipocalin at inception of renal replacement therapy predicts survival in critically ill patients with acute kidney injury. Critical care 14: R9, 2010. 50. Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Saito Y, Yoshioka T, Ogawa Y, Imamaki H, Kusakabe T, Ebihara K, Omata M, Satoh N, Sugawara A, Barasch J, and Nakao K. Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons. Kidney international 75: 285-294, 2009. 51. Le Cabec V, Calafat J, and Borregaard N. Sorting of the specific granule protein, NGAL, during granulocytic maturation of HL-60 cells. Blood 89: 2113-2121, 1997. 52. Lee YJ, Hu YY, Lin YS, Chang CT, Lin FY, Wong ML, Kuo-Hsuan H, and Hsu WL. Urine neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute canine kidney injury. BMC veterinary research 8: 248, 2012. 53. Leng X, Wu Y, and Arlinghaus RB. Relationships of lipocalin 2 with breast tumorigenesis and metastasis. Journal of cellular physiology 226: 309-314, 2011. 54. Lentini P, de Cal M, Clementi A, D''Angelo A, and Ronco C. Sepsis and AKI in ICU Patients: The Role of Plasma Biomarkers. Critical care research and practice 2012: 856401, 2012. 55. Lippi G, Salvagno GL, and Banfi G. Serum but not urine concentration of neutrophil gelatinase-associated lipocalin is influenced by acute leukocyte variations. Leukemia & lymphoma 53: 1643-1645, 2012. 56. Manicourt DH, Fujimoto N, Obata K, and Thonar EJ. Levels of circulating collagenase, stromelysin-1, and tissue inhibitor of matrix metalloproteinases 1 in patients with rheumatoid arthritis. Relationship to serum levels of antigenic keratan sulfate and systemic parameters of inflammation. Arthritis and rheumatism 38: 1031-1039, 1995. 57. Martensson J, Bell M, Oldner A, Xu S, Venge P, and Martling CR. Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury. Intensive care medicine 36: 1333-1340, 2010. 58. Martensson J, Xu S, Bell M, Martling CR, and Venge P. Immunoassays distinguishing between HNL/NGAL released in urine from kidney epithelial cells and neutrophils. Clinica chimica acta; international journal of clinical chemistry 413: 1661-1667, 2012. 59. Miethke M, and Skerra A. Neutrophil gelatinase-associated lipocalin expresses antimicrobial activity by interfering with L-norepinephrine-mediated bacterial iron acquisition. Antimicrobial agents and chemotherapy 54: 1580-1589, 2010. 60. Milo G, Katchman EA, Paul M, Christiaens T, Baerheim A, and Leibovici L. Duration of antibacterial treatment for uncomplicated urinary tract infection in women. Cochrane database of systematic reviews CD004682, 2005. 61. Mira E, Lacalle RA, Buesa JM, de Buitrago GG, Jimenez-Baranda S, Gomez-Mouton C, Martinez AC, and Manes S. Secreted MMP9 promotes angiogenesis more efficiently than constitutive active MMP9 bound to the tumor cell surface. Journal of cell science 117: 1847-1857, 2004. 62. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, and Devarajan P. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365: 1231-1238, 2005. 63. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, and Devarajan P. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. Journal of the American Society of Nephrology : JASN 14: 2534-2543, 2003. 64. Mishra J, Mori K, Ma Q, Kelly C, Yang J, Mitsnefes M, Barasch J, and Devarajan P. Amelioration of ischemic acute renal injury by neutrophil gelatinase-associated lipocalin. Journal of the American Society of Nephrology : JASN 15: 3073-3082, 2004. 65. Moreno-Navarrete JM, Manco M, Ibanez J, Garcia-Fuentes E, Ortega F, Gorostiaga E, Vendrell J, Izquierdo M, Martinez C, Nolfe G, Ricart W, Mingrone G, Tinahones F, and Fernandez-Real JM. Metabolic endotoxemia and saturated fat contribute to circulating NGAL concentrations in subjects with insulin resistance. International journal of obesity 34: 240-249, 2010. 66. Mori K, Lee HT, Rapoport D, Drexler IR, Foster K, Yang J, Schmidt-Ott KM, Chen X, Li JY, Weiss S, Mishra J, Cheema FH, Markowitz G, Suganami T, Sawai K, Mukoyama M, Kunis C, D’Agati V, Devarajan P, and Barasch J. Endocytic delivery of lipocalin-siderophore-iron complex rescues the kidney from ischemia-reperfusion injury. Journal of Clinical Investigation 115: 610-621, 2005. 67. Mori K, and Nakao K. Neutrophil gelatinase-associated lipocalin as the real-time indicator of active kidney damage. Kidney international 71: 967-970, 2007. 68. Munir MU, Khan DA, Khan FA, and Shahab Naqvi SM. Rapid detection of acute kidney injury by urinary neutrophil gelatinase-associated lipocalin after cardiopulmonary bypass surgery. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP 23: 103-106, 2013. 69. Nairz M, Theurl I, Schroll A, Theurl M, Fritsche G, Lindner E, Seifert M, Crouch ML, Hantke K, Akira S, Fang FC, and Weiss G. Absence of functional Hfe protects mice from invasive Salmonella enterica serovar Typhimurium infection via induction of lipocalin-2. Blood 114: 3642-3651, 2009. 70. Nickolas TL, Forster CS, Sise ME, Barasch N, Valle DS, Viltard M, Buchen C, Kupferman S, Carnevali ML, Bennett M, Mattei S, Bovino A, Argentiero L, Magnano A, Devarajan P, Mori K, Erdjument-Bromage H, Tempst P, Allegri L, and Barasch J. NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease. Kidney international 82: 718-722, 2012. 71. Nickolas TL, O''Rourke MJ, Yang J, Sise ME, Canetta PA, Barasch N, Buchen C, Khan F, Mori K, Giglio J, Devarajan P, and Barasch J. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Annals of internal medicine 148: 810-819, 2008. 72. Provatopoulou X, Gounaris A, Kalogera E, Zagouri F, Flessas I, Goussetis E, Nonni A, Papassotiriou I, and Zografos G. Circulating levels of matrix metalloproteinase-9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and their complex MMP-9/NGAL in breast cancer disease. BMC cancer 9: 390, 2009. 73. Remuzzi G, Ruggenenti P, and Benigni A. Understanding the nature of renal disease progression. Kidney international 51: 2-15, 1997. 74. Ruilope LM, van Veldhuisen DJ, Ritz E, and Luscher TF. Renal function: the Cinderella of cardiovascular risk profile. Journal of the American College of Cardiology 38: 1782-1787, 2001. 75. Schinstock CA, Semret MH, Wagner SJ, Borland TM, Bryant SC, Kashani KB, Larson TS, and Lieske JC. Urinalysis is more specific and urinary neutrophil gelatinase-associated lipocalin is more sensitive for early detection of acute kidney injury. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2012. 76. Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P, and Barasch J. Dual action of neutrophil gelatinase-associated lipocalin. Journal of the American Society of Nephrology : JASN 18: 407-413, 2007. 77. Seth P, Porter D, Lahti-Domenici J, Geng Y, Richardson A, and Polyak K. Cellular and molecular targets of estrogen in normal human breast tissue. Cancer research 62: 4540-4544, 2002. 78. Shapiro NI, Trzeciak S, Hollander JE, Birkhahn R, Otero R, Osborn TM, Moretti E, Nguyen HB, Gunnerson KJ, Milzman D, Gaieski DF, Goyal M, Cairns CB, Ngo L, and Rivers EP. A prospective, multicenter derivation of a biomarker panel to assess risk of organ dysfunction, shock, and death in emergency department patients with suspected sepsis. Critical care medicine 37: 96-104, 2009. 79. Sopata I, and Wize J. A latent gelatin specific proteinase of human leucocytes and its activation. Biochimica et biophysica acta 571: 305-312, 1979. 80. Tong Z, Kunnumakkara AB, Wang H, Matsuo Y, Diagaradjane P, Harikumar KB, Ramachandran V, Sung B, Chakraborty A, Bresalier RS, Logsdon C, Aggarwal BB, Krishnan S, and Guha S. Neutrophil gelatinase-associated lipocalin: a novel suppressor of invasion and angiogenesis in pancreatic cancer. Cancer research 68: 6100-6108, 2008. 81. Vail DM, Allen TA, and Weiser G. Applicability of leukocyte esterase test strip in detection of canine pyuria. Journal of the American Veterinary Medical Association 189: 1451-1453, 1986. 82. Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, and Lee HT. Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology 105: 485-491, 2006. 83. Xu SY, Carlson M, Engstrom A, Garcia R, Peterson CG, and Venge P. Purification and characterization of a human neutrophil lipocalin (HNL) from the secondary granules of human neutrophils. Scandinavian journal of clinical and laboratory investigation 54: 365-376, 1994. 84. Yan L, Borregaard N, Kjeldsen L, and Moses MA. The high molecular weight urinary matrix metalloproteinase (MMP) activity is a complex of gelatinase B/MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL). Modulation of MMP-9 activity by NGAL. The Journal of biological chemistry 276: 37258-37265, 2001. 85. Yang HN, Boo CS, Kim MG, Jo SK, Cho WY, and Kim HK. Urine neutrophil gelatinase-associated lipocalin: an independent predictor of adverse outcomes in acute kidney injury. American journal of nephrology 31: 501-509, 2010. 86. Yang J, Goetz D, Li JY, Wang W, Mori K, Setlik D, Du T, Erdjument-Bromage H, Tempst P, Strong R, and Barasch J. An iron delivery pathway mediated by a lipocalin. Molecular cell 10: 1045-1056, 2002. 87. Yilmaz A, Sevketoglu E, Gedikbasi A, Karyagar S, Kiyak A, Mulazimoglu M, Aydogan G, Ozpacaci T, and Hatipoglu S. Early prediction of urinary tract infection with urinary neutrophil gelatinase associated lipocalin. Pediatric nephrology 24: 2387-2392, 2009.
摘要: 
Neutrophil gelatinase-associated lipocalin(NGAL)為隸屬於lipocalin家族之大小約25 kDa分泌性醣蛋白,最初由人類嗜中性球中被發現。許多人醫研究皆指出,腎臟受損後NGAL會於短時間大量表現於血液及尿液中,因此NGAL於早期預測腎衰竭之角色也備受重視。除腎臟來源外,NGAL也會由嗜中性球分泌,有人醫研究發現,下泌尿道感染時尿中NGAL濃度的上升可作為早期偵測下泌尿道感染的指標之一,換句話說,泌尿道感染可能成為NGAL於腎臟疾病應用之干擾因子。NGAL以monomer、dimer及NGAL/MMP-9複合物以上3種形式存在,近期有研究以immunoblotting方式分析發現,腎臟上皮細胞分泌之NGAL以monomer為主,而嗜中性球分泌之型態多以dimer為主。本實驗室已成功製備出可用於偵測犬NGAL之多株抗體且建立ELISA系統,並證明NAGL可成為評估犬之腎衰竭一個有用的生化檢測;然而,白血球數量對犬尿中NGAL濃度及型態之影響仍尚未明瞭。本次實驗目的有二:第一,利用實驗室建立之ELISA系統評估血液及尿中白血球對尿中NGAL的影響;第二,以西方墨點法分析犬尿中NGAL型態,及表現型態是否與腎衰竭及尿中白球有關。由中興大學獸醫教學醫院共收集70隻就診犬之尿液樣本(24隻為腎衰竭病例[RF],19隻為膿尿病例[PYU],17隻為腎衰竭同時併發膿尿之病例[RF-PYU],10隻為非腎衰竭及膿尿之其他疾病病例),以及11隻健康犬之尿液做為健康對照組。由統計分析結果得知,血中白血球數目與尿中NGAL濃度不具相關性(r2 <0.1);然而,膿尿病例之尿中NGAL濃度則顯著高於對照組(p <0.01)(15.35 ng/mL [IQR 27.66] vs. 3.92 ng/mL [IQR 9.05]);另外,腎衰竭及腎衰竭同時併發膿尿之病例尿中NGAL濃度顯著高於對照組(RF:23.77 ng/mL [IQR 32.73]、RF-PYU:18.97 ng/mL [IQR 70.32]),但兩組與膿尿病例則無顯著差異。西方墨點法分析所有尿液樣本發現,犬尿中NGAL存在3種型態:monomer(25 kDa)、dimer(50 kDa)及NGAL/MMP-9複合物(150 kDa)。在所有腎衰竭的病例中(RF及RF-PYU),monomer出現的比例顯著高於非腎衰竭病例;而所有膿尿的病例中(PYU及RF-PYU)出現dimer的比例則顯著高於為非膿尿病例。以上結果顯示,犬尿中白血球數目會影響尿中NGAL之濃度;而monomer的出現與腎衰竭有關,dimer的出現則較與尿中白血球有關,藉此有助於辨別犬尿中NGAL來源,以提高尿中NGAL於犬腎衰竭相關臨床應用。

Neutrophil gelatinase-associated lipocalin (NGAL), a 25 kDa glycoprotein existing as monomer, homodimer and NGAL/MMP-9 complex, was found highly accumulated in human and mouse proximal tubule during acute tubular necrosis, thus regarded as an early predictor of acute kidney injury (AKI). Recent studies showed that the major molecular form of NGAL secreted by neutrophils is dimeric, whereas the major form secreted by kidney epithelial cells is monomeric. The aim of this study is to evaluate possible factors affecting the concentration and forms of urine NGAL (uNGAL). Urine samples of 70 dogs from Veterinary Medical Teaching Hospital of National Chung Hsing University (24 with renal failure (RF), 19 with pyuria (PYU), 17 with both renal failure and pyuria (RF-PYU), 10 with other diseases) and 11 healthy dogs as control were analyzed by western blotting and home-made ELISA for evaluation of NGAL concentration and forms in urine. Results show no correlation between blood leukocyte counts and uNGAL (r2 <0.1); however, patients with pyuria have higher uNGAL concentration then control (p <0.01). uNGAL in RF and RF-PYU patients were significantly higher than control (p <0.01), but with no significant difference between PYU patients. Three forms of uNGAL were identified in canine urine: monomer, dimer and NGAL/MMP-9 complex, and the rate of monomer in patients with renal failure (RF and RF-PYU) is significantly higher than patients without renal failure (p <0.01) whereas the rate of dimer in patients with pyuria (PYU and RF-PYU) is significantly higher than patients without pyuria(p <0.01). In conclusion, urine leucocyte may cause elevation of uNGAL concentration and could be a confounding factor of uNGAL in clinical use. Moreover, renal failure is associated with the presence of uNGAL monomer whereas dimer is associated with the presence of urine leukocyte, which indicates that the forms of uNGAL may aids in the differentiation of renal failure and pyuria.
ii
URI: http://hdl.handle.net/11455/14484
其他識別: U0005-2307201302211700
Appears in Collections:獸醫學系所

Show full item record
 

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.