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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
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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.
其他識別: U0005-2307201302211700
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