NGAL与肾脏疾病相关性的研究进展
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摘要
中性粒细胞明胶酶相关脂质运载蛋白(NGAL)作为载脂蛋白家族的新成员,通过调节肾间充质细胞向肾小管上皮细胞转化、抑制肾脏纤维化、清除氧自由基参与肾脏的损伤修复。国内外研究报道,揭示了在急性肾损伤(AKI)及慢性肾脏病(CKD)等多种肾脏疾病发生发展中,在传统肾功能指标变化之前,尿液及血液中即可检测到NGAL浓度的变化,可见通过检测NGAL浓度对多种肾脏疾病的早期诊断、治疗及预后具有重要意义。
Neutrophil gelatinase-associated lipocalin(NGAL), a novel member of the apolipoprotein family, can participate in the repair of kidney damage by means of regulating the transformation of renal mesenchymal cells into renal tubular epithelial cells, inhibiting kidney fibrosis, and clearing oxygen free radicals. Studies in the domestic and abroad have revealed that during the initiation and development of kidney disease such as acute kindey injury(AKI) and chronic kidney disease(CKD), changes in NGAL levels can be detected in urine and blood before the change of traditional renal function index. It can be seen that the detection of changes in NGAL concentration is of great significance for the early diagnosis, treatment and prognosis of multiple kidney diseases.The biological characteristics of NGAL and its relationship with kidney disease are reviewed.
Neutrophil gelatinase-associated lipocalin(NGAL), a novel member of the apolipoprotein family, can participate in the repair of kidney damage by means of regulating the transformation of renal mesenchymal cells into renal tubular epithelial cells, inhibiting kidney fibrosis, and clearing oxygen free radicals. Studies in the domestic and abroad have revealed that during the initiation and development of kidney disease such as acute kindey injury(AKI) and chronic kidney disease(CKD), changes in NGAL levels can be detected in urine and blood before the change of traditional renal function index. It can be seen that the detection of changes in NGAL concentration is of great significance for the early diagnosis, treatment and prognosis of multiple kidney diseases.The biological characteristics of NGAL and its relationship with kidney disease are reviewed.
引文
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[8]Devarajan P.Neutrophil gelatinase-associated lipocalin:new paths for an old shuttle.Cancer Ther,2007,5:463-70
[9]Auguet T,Quintero Y,Terra X,et al.Upregulation of lipocalin 2 in adipose tissues of severely obese women:positive relationship with proinflammatory cytokines.Obesity(Silver Spring),2011,19:2295-300
[10]Nuntagowat C,Leelawat K,Tohtong R.NGAL knockdown by siRNA in human cholangiocarcinoma cells suppressed invasion by reducing NGAL/MMP-9 complex fomation.Clin Exp Metastasis,2010,27:295-305
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[12]Yang J,Goetz D,Li JY,et al.An iron delivery pathway mediated by a lipocalin.Mol Cell,2002,10:1045-56
[13]Roudkenar MH,Kuwahara Y,Baba T,et al.Oxidative stress induced lipocalin 2 gene expression:addressing its expression under the harmful conditions.J Radiat Res,2007,48:39-44
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[15]Jha V,Chugh KS.Community-acquired acute kidney injury in Asia.Semin Nephrol,2008,28:330-47
[16]Paragas N,Qiu A,Zhang Q,et al.The NGAL reporter mouse detects the response of the kidney to injury in real time.Nat Med,2011,17:216-22
[17]Han M,Li Y,Liu M,et al.Renal neutrophil gelatinaseassociated lipocalin expression in lipopolysaccharideinduced acute kidney injury in the rat.BMC Nephrol,2012,13:25
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[20]Ning L,Li Z,Wei D,et al.Urinary semaphorin 3A as an early biomarker to predict contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention.Braz J Med Biol Res,2018,51:e6487
[21]Urbschat A,Gauer S,Paulus P,et al.Serum and urinary NGAL but not Kim-1 raises in human postrenal AKI.Eur J Clin Invest,2014,44:652-9
[22]Izadi A,Yousefifard M,Nakhjavan-Shahraki B,et al.Diagnostic value of urinary neutrophil gelatinaseassociated lipocalin(NGAL)in detection of pediatric acute kidney injury:a systematic review and metaanalysis.Int J Pediatr,2016,4:3875-95
[23]Izadi A,Yousefifard M,Nakhjavan-Shahraki B,et al.Value of plasma/serum neutrophil gelatinase-associated lipocalin in detection of pediatric acute kidney injury:a systematic review and meta-analysis.Int J Pediatr,2016,4:3815-36
[24]Bostan Gayret?,Ta?demir M,Erol M,et al.Are there any new reliable markers to detect renal injury in obese children?.Ren Fail,2018,40:416-22
[25]Parikh CR,Coca SG,Thiessen-Philbrook H,et al.Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery.J Am Soc Nephrol,2011,22:1748-57
[26]Antonucci E,Lippi G,Ticinesi A,et al.Neutrophil gelatinase-associated lipocalin(NGAL):a promising biomarker for the early diagnosis of acute kidney injury(AKI).Acta Biomed,2014,85:289-94
[27]Belcher JM.Acute kidney injury in liver disease:role of biomarkers.Adv Chronic Kidney Dis,2015,22:368-75
[28]Gungor G,Ataseven H,Demir A,et al.Neutrophil gelatinase-associated lipocalin in prediction of mortality in patients with hepatorenal syndrome:a prospective observational study.Liver Int,2014,34:49-57
[29]Klein SJ,Brandtner AK,Lehner GF.Biomarkers for prediction of renal replacement therapy in acute kidney injury:a systematic review and meta-analysis.Intersive Care Med,2018,44:323-36
[30]Zhang L,Wang F,Wang L,et al.Prevalence of chronic kidney disease in China:a cross-sectional survey.Lancet,2012,379:815-22
[31]Yang HN,Boo CS,Kim MG,et al.Urine neutrophil gelatinase-associated lipocalin:an independent predictor of adverse outcomes in acute kidney injury.Am J Nephrol,2010,31:501-9
[32]曾健英,童俊容,何凤,等.中性粒细胞明胶酶相关载脂蛋白对糖尿病肾病早期诊断的意义.中国糖尿病杂志,2011,19:27-30
[33]Woo KS,Choi JL,Kim BR,et al.Urinary neutrophil gelatinase-associated lipocalin levels in comparison with glomerular filtration rate for evaluation of renal function in patients with diabetic chronic kidney disease.Diabetes Metab J,2012,36:307-13
[34]Rheeh H,Shin N,Shin MJ,et al.High serum and urine neutrophil gelatinase-associated lipocalin levels are independent predictors of renal progression in patients with immunoglobulin a nephropathy.Korean J Intern Med,2015,30:354-61
[35]Kaul A,Behera MR,Rai MK,et al.Neutrophil gelatinaseassociated lipocalin:as a predictor of early diabetic nephropathy in type 2 diabetes mellitus.Indian J Nephrol,2018,28:53-60
[36]E1 Shahawy MS,Hemida MH,Abdel-Hafez HA,et al.Urinary neutrophil gelatinase-associated lipocalin as a marker for disease activity in lupus nephritis.Scand J Clin Lab Invest,2018,78:264-8
[37]Satirapoj B,Kitiyakara C,Leelahavanichkul A,et al.Urine neutrophil gelatinase-associated lipocalin to predict renal response after induction therapy in active lupus nephritis.BMC Nephrol,2017,18:263
[38]Kraydaschenko OV,Abramov AV,Dolinnaya MA.Role of biomarkers in estimation of renal tubulointerstitial tissue damage in patients with chronic glomerulonephritis.Lik Sprava,2015,3-4:61-5
[39]Goknar N,Oktem F,Ozgen IT,et al.Determination of early urinary renal injury markers in obese children.Pediatr Nephrol,2015,30:139-44
[40]张科,刘彧,张春,等.尿NGAL与CKD肾小管间质损伤的相关性研究.检验医学,2015,4:327-30
[41]Ding Y,Nie LM,Pang Y,et al.Composite urinary biomarkers to predict pathological tubulointerstitial lesions in lupus nephritis.Lupus,2018,27:1778-89
[42]李惊子,王素霞,秦小棋,等.IgA肾病尿沉渣谱与肾脏病理改变的相关关系.中华肾脏病杂志,2015,31:91-6
[43]Martino F,Scalzotto E,Giavarina D,et al.The role of NGAL in peritoneal dialysis effluent in early diagnosis of peritonitis:case-control study in peritoneal dialysis patients.Perit Dial Int,2015,35:559-65
[44]黄文,李占园,周志宏,等.维持性血透患者血清NGAL水平与透析充分性及微炎症状态的相关性.实用医学杂志,2012,28:3079-81
[45]Ramirez-Sandoval JC,Herrington W,Morales-Buenrostro LE.Neutrophil gelatinase-associated lipocalin in kidney transplantation:a review.Transplant Rev(Orlando),2015,29:139-44
[46]Pedersen KR,Ravn HB,Hjortdal VE,et al.Neutrophil gelatinase-associated lipocalin(NGAL):validation of commercially available ELISA.Scand J Clin Lab Invest,2010,70:374-82
[47]Parikh A,Rizzo JA,Canetta P,et al.Dose NGAL reduce costs?A cost analysis of urine NGAL(uNGAL)&secrum creatinine(sCr)for acute kidney injury(AKI)diagnosis.PLoS One,2017,12:e0178091
[48]Cullen MR,Murray PT,Fitzgibbon MC.Establishment of a reference interval for urinary neutrophil gelatinaseassociated lipocalin.Ann Clin Biochem,2012,49:190-3
[2]Kjeldsen L,Johnsen AH,Sengel?v H,et al.Isolation and primary structure of NGAL,a novel protein associated with human neutrophil gelatinase.J Biol Chem,1993,268:10425-32
[3]Cowland JB,Borregaard N.Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans.Genomics,1997,45:17-23
[4]Singer E,MarkóL,Paragas N,et al.Neutrophil gelatinaseassociated lipocalin:pathophysiology and clinical applications.Acta Physiol(Oxf),2013,207:663-72
[5]Virzi GM,Clementi A,de Cal M,et al.Genomics and biological activity of neutrophil gelatinase-associated lipocalin in several clinical settings.Blood Purif,2013,35:139-43
[6]Cai L,Rubin J,Han W,et al.The origin of multiple molecular forms in urine of HNL/NGAL.Clin J Am Soc Nephrol,2010,5:2229-35
[7]龚淑文,沈水娟,何剑零.NGAL的结构功能及其在慢性肾脏病的作用.中国中西医结合肾病杂志,2013,14:354-6
[8]Devarajan P.Neutrophil gelatinase-associated lipocalin:new paths for an old shuttle.Cancer Ther,2007,5:463-70
[9]Auguet T,Quintero Y,Terra X,et al.Upregulation of lipocalin 2 in adipose tissues of severely obese women:positive relationship with proinflammatory cytokines.Obesity(Silver Spring),2011,19:2295-300
[10]Nuntagowat C,Leelawat K,Tohtong R.NGAL knockdown by siRNA in human cholangiocarcinoma cells suppressed invasion by reducing NGAL/MMP-9 complex fomation.Clin Exp Metastasis,2010,27:295-305
[11]蒋奶贵,许丽艳,郭明洲,等.肿瘤相关蛋白NGAL的生物学特征.胃肠病学和肝病学杂志,2010,19:297-301
[12]Yang J,Goetz D,Li JY,et al.An iron delivery pathway mediated by a lipocalin.Mol Cell,2002,10:1045-56
[13]Roudkenar MH,Kuwahara Y,Baba T,et al.Oxidative stress induced lipocalin 2 gene expression:addressing its expression under the harmful conditions.J Radiat Res,2007,48:39-44
[14]Adiyanti SS,Loho T.Acute kidney injury(AKI)biomarker.Acta Med Indones,2012,44:246-55
[15]Jha V,Chugh KS.Community-acquired acute kidney injury in Asia.Semin Nephrol,2008,28:330-47
[16]Paragas N,Qiu A,Zhang Q,et al.The NGAL reporter mouse detects the response of the kidney to injury in real time.Nat Med,2011,17:216-22
[17]Han M,Li Y,Liu M,et al.Renal neutrophil gelatinaseassociated lipocalin expression in lipopolysaccharideinduced acute kidney injury in the rat.BMC Nephrol,2012,13:25
[18]Singer E,Elger A,Elitok S,et al.Urinary neutrophil gelatinase-associated lipocalin distinguishes pre-renal from intrinsic renal failure and predicts outcomes.Kindey Int,2011,80:405-14
[19]Park SY,Eom JS,Lee JS,et al.Neutrophil gelatinaseassociated lipocalin as a predictor of acute kidney injury in patients during treatment with colistimethate sodium.Infect Chemother,2018,50:128-37
[20]Ning L,Li Z,Wei D,et al.Urinary semaphorin 3A as an early biomarker to predict contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention.Braz J Med Biol Res,2018,51:e6487
[21]Urbschat A,Gauer S,Paulus P,et al.Serum and urinary NGAL but not Kim-1 raises in human postrenal AKI.Eur J Clin Invest,2014,44:652-9
[22]Izadi A,Yousefifard M,Nakhjavan-Shahraki B,et al.Diagnostic value of urinary neutrophil gelatinaseassociated lipocalin(NGAL)in detection of pediatric acute kidney injury:a systematic review and metaanalysis.Int J Pediatr,2016,4:3875-95
[23]Izadi A,Yousefifard M,Nakhjavan-Shahraki B,et al.Value of plasma/serum neutrophil gelatinase-associated lipocalin in detection of pediatric acute kidney injury:a systematic review and meta-analysis.Int J Pediatr,2016,4:3815-36
[24]Bostan Gayret?,Ta?demir M,Erol M,et al.Are there any new reliable markers to detect renal injury in obese children?.Ren Fail,2018,40:416-22
[25]Parikh CR,Coca SG,Thiessen-Philbrook H,et al.Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery.J Am Soc Nephrol,2011,22:1748-57
[26]Antonucci E,Lippi G,Ticinesi A,et al.Neutrophil gelatinase-associated lipocalin(NGAL):a promising biomarker for the early diagnosis of acute kidney injury(AKI).Acta Biomed,2014,85:289-94
[27]Belcher JM.Acute kidney injury in liver disease:role of biomarkers.Adv Chronic Kidney Dis,2015,22:368-75
[28]Gungor G,Ataseven H,Demir A,et al.Neutrophil gelatinase-associated lipocalin in prediction of mortality in patients with hepatorenal syndrome:a prospective observational study.Liver Int,2014,34:49-57
[29]Klein SJ,Brandtner AK,Lehner GF.Biomarkers for prediction of renal replacement therapy in acute kidney injury:a systematic review and meta-analysis.Intersive Care Med,2018,44:323-36
[30]Zhang L,Wang F,Wang L,et al.Prevalence of chronic kidney disease in China:a cross-sectional survey.Lancet,2012,379:815-22
[31]Yang HN,Boo CS,Kim MG,et al.Urine neutrophil gelatinase-associated lipocalin:an independent predictor of adverse outcomes in acute kidney injury.Am J Nephrol,2010,31:501-9
[32]曾健英,童俊容,何凤,等.中性粒细胞明胶酶相关载脂蛋白对糖尿病肾病早期诊断的意义.中国糖尿病杂志,2011,19:27-30
[33]Woo KS,Choi JL,Kim BR,et al.Urinary neutrophil gelatinase-associated lipocalin levels in comparison with glomerular filtration rate for evaluation of renal function in patients with diabetic chronic kidney disease.Diabetes Metab J,2012,36:307-13
[34]Rheeh H,Shin N,Shin MJ,et al.High serum and urine neutrophil gelatinase-associated lipocalin levels are independent predictors of renal progression in patients with immunoglobulin a nephropathy.Korean J Intern Med,2015,30:354-61
[35]Kaul A,Behera MR,Rai MK,et al.Neutrophil gelatinaseassociated lipocalin:as a predictor of early diabetic nephropathy in type 2 diabetes mellitus.Indian J Nephrol,2018,28:53-60
[36]E1 Shahawy MS,Hemida MH,Abdel-Hafez HA,et al.Urinary neutrophil gelatinase-associated lipocalin as a marker for disease activity in lupus nephritis.Scand J Clin Lab Invest,2018,78:264-8
[37]Satirapoj B,Kitiyakara C,Leelahavanichkul A,et al.Urine neutrophil gelatinase-associated lipocalin to predict renal response after induction therapy in active lupus nephritis.BMC Nephrol,2017,18:263
[38]Kraydaschenko OV,Abramov AV,Dolinnaya MA.Role of biomarkers in estimation of renal tubulointerstitial tissue damage in patients with chronic glomerulonephritis.Lik Sprava,2015,3-4:61-5
[39]Goknar N,Oktem F,Ozgen IT,et al.Determination of early urinary renal injury markers in obese children.Pediatr Nephrol,2015,30:139-44
[40]张科,刘彧,张春,等.尿NGAL与CKD肾小管间质损伤的相关性研究.检验医学,2015,4:327-30
[41]Ding Y,Nie LM,Pang Y,et al.Composite urinary biomarkers to predict pathological tubulointerstitial lesions in lupus nephritis.Lupus,2018,27:1778-89
[42]李惊子,王素霞,秦小棋,等.IgA肾病尿沉渣谱与肾脏病理改变的相关关系.中华肾脏病杂志,2015,31:91-6
[43]Martino F,Scalzotto E,Giavarina D,et al.The role of NGAL in peritoneal dialysis effluent in early diagnosis of peritonitis:case-control study in peritoneal dialysis patients.Perit Dial Int,2015,35:559-65
[44]黄文,李占园,周志宏,等.维持性血透患者血清NGAL水平与透析充分性及微炎症状态的相关性.实用医学杂志,2012,28:3079-81
[45]Ramirez-Sandoval JC,Herrington W,Morales-Buenrostro LE.Neutrophil gelatinase-associated lipocalin in kidney transplantation:a review.Transplant Rev(Orlando),2015,29:139-44
[46]Pedersen KR,Ravn HB,Hjortdal VE,et al.Neutrophil gelatinase-associated lipocalin(NGAL):validation of commercially available ELISA.Scand J Clin Lab Invest,2010,70:374-82
[47]Parikh A,Rizzo JA,Canetta P,et al.Dose NGAL reduce costs?A cost analysis of urine NGAL(uNGAL)&secrum creatinine(sCr)for acute kidney injury(AKI)diagnosis.PLoS One,2017,12:e0178091
[48]Cullen MR,Murray PT,Fitzgibbon MC.Establishment of a reference interval for urinary neutrophil gelatinaseassociated lipocalin.Ann Clin Biochem,2012,49:190-3