中性粒细胞明胶酶相关脂质运载蛋白在克罗恩病临床诊断中的应用价值

doi:10.11958/20240286

天津医药 ›› 2024, Vol. 52 ›› Issue (10): 1116-1120.doi: 10.11958/20240286

• 综述 • 上一篇

中性粒细胞明胶酶相关脂质运载蛋白在克罗恩病临床诊断中的应用价值

麻凯(), 姚一博, 王琛^△()

上海中医药大学附属龙华医院肛肠科（邮编200032）

收稿日期:2024-03-10 修回日期:2024-04-10 出版日期:2024-10-15 发布日期:2024-10-14
通讯作者: △ E-mail：wangchen_longhua@163.com
作者简介:麻凯（1992），男，博士在读，主要从事炎症性肠道疾病的临床与基础方面研究。E-mail：mk9205010524@163.com
基金资助:
上海市重中之重临床研究中心建设项目(2023ZZ02003);上海市级医院中医外科临床能力促进与提升专科联盟(SHDC22021316-A);国家中医药管理局高水平中医药重点学科建设项目——中医肛肠病学(ZYYZDXK-2023064)

Application value of neutrophil gelatinase associated lipocalin in clinical diagnosis of Crohn's disease

MA Kai(), YAO Yibo, WANG Chen^△()

Department of Anal and Intestinal Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China

Received:2024-03-10 Revised:2024-04-10 Published:2024-10-15 Online:2024-10-14
Contact: △ E-mail：wangchen_longhua@163.com

麻凯, 姚一博, 王琛. 中性粒细胞明胶酶相关脂质运载蛋白在克罗恩病临床诊断中的应用价值[J]. 天津医药, 2024, 52(10): 1116-1120.

MA Kai, YAO Yibo, WANG Chen. Application value of neutrophil gelatinase associated lipocalin in clinical diagnosis of Crohn's disease[J]. Tianjin Medical Journal, 2024, 52(10): 1116-1120.

摘要/Abstract

摘要：

克罗恩病（CD）是一种以慢性、非特异性炎症为特征的自身免疫性肠道疾病，其病因及发病机制仍未明确。中性粒细胞明胶酶相关脂质运载蛋白（NGAL）是从中性粒细胞中分离出的一种分泌性糖蛋白，广泛参与肠道炎症反应、细胞凋亡、肿瘤进展等病理生理过程。NGAL在CD的临床诊断及活动性监测方面具有生物标志物的潜能。就NGAL在CD不同临床样本中的应用价值进行综述，以期为CD的临床诊治提供参考。

关键词: Crohn病, 脂笼蛋白质2, 诊断, 中性粒细胞明胶酶相关脂质运载蛋白

Abstract:

Crohn's disease (CD) is an autoimmune intestinal disease characterised by chronic and non-specific inflammation, and the exact etiology and pathogenesis are still unclear. Neutrophil gelatinase associated lipocalin (NGAL), a secreted glycoprotein and isolated from neutrophils, is widely involved in pathophysiological processes such as intestinal inflammation response, apoptosis and tumour progression. It has been found that NGAL has the potential to be a clinical biological marker in clinical diagnosis and monitoring of CD activity. Therefore, this paper reviews the application value of NGAL in different clinical samples of CD, in order to provide reference for clinical diagnosis and treatment of CD.

Key words: Crohn disease, lipocalin-2, diagnosis, neutrophil gelatinase associated lipocalin

中图分类号:

R574

图/表 1

参考文献 41

[1]	BUIE M J, QUAN J, WINDSOR J W, et al. Global hospitalization trends for Crohn's disease and ulcerative colitis in the 21st century:a systematic review with temporal analyses[J]. Clin Gastroenterol Hepatol, 2023, 21(9):2211-2221. doi:10.1016/j.cgh.2022.06.030.
[2]	LEWIS J D, PARLETT L E, JONSSON FUNK M L, et al. Incidence,prevalence,and racial and ethnic distribution of inflammatory bowel disease in the United States[J]. Gastroenterology, 2023, 165(5):1197-1205.e2. doi:10.1053/j.gastro.2023.07.003.
[3]	XU L, HE B, SUN Y, et al. Incidence of inflammatory bowel disease in urban China:a nationwide population-based study[J]. Clin Gastroenterol Hepatol, 2023, 21(13):3379-3386.e29. doi:10.1016/j.cgh.2023.08.013.
[4]	GILLILAND A, CHAN J J, DE WOLFE T J, et al. Pathobionts in inflammatory bowel disease:origins,underlying mechanisms,and implications for clinical care[J]. Gastroenterology, 2024, 166(1):44-58. doi:10.1053/j.gastro.2023.09.019.
[5]	RUDBAEK J J, AGRAWAL M, TORRES J, et al. Deciphering the different phases of preclinical inflammatory bowel disease[J]. Nat Rev Gastroenterol Hepatol, 2024, 21(2):86-100. doi:10.1038/s41575-023-00854-4.
[6]	中华医学会消化病学分会炎症性肠病学组, 中国炎症性肠病诊疗质量控制评估中心. 中国克罗恩病诊治指南(2023年·广州)[J]. 中华炎性肠病杂志(中英文), 2024, 8(1):2-32.
	Inflammatory Bowel Disease Group, Chinese Society of Gastroenterology, Chinese Medical Association; Inflammatory Bowel Disease Quality Control Center of China. Chinese clinical practice guideline on the management of Crohn's disease(2023,Guangzhou)[J]. Chin J Inflamm Bowel Dis, 2024, 8(1):2-32. doi:10.3760/cma.j.cn101480-20240108-00006.
[7]	KAMMERMEIER J, LAMB C A, JONES K, et al. Genomic diagnosis and care co-ordination for monogenic inflammatory bowel disease in children and adults:consensus guideline on behalf of the British Society of Gastroenterology and British Society of Paediatric Gastroenterology,Hepatology and Nutrition[J]. Lancet Gastroenterol Hepatol, 2023, 8(3):271-286. doi:10.1016/S2468-1253(22)00337-5.
[8]	ROMEJKO K, MARKOWSKA M, NIEMCZYK S. The review of current knowledge on neutrophil gelatinase-associated lipocalin(NGAL)[J]. Int J Mol Sci, 2023, 24(13):10470. doi:10.3390/ijms241310470.
[9]	GAMBINO C, PIANO S, STENICO M, et al. Diagnostic and prognostic performance of urinary neutrophil gelatinase-associated lipocalin in patients with cirrhosis and acute kidney injury[J]. Hepatology, 2023, 77(5):1630-1638. doi:10.1002/hep.32799.
[10]	ASAF S, MAQSOOD F, JALIL J, et al. Lipocalin 2-not only a biomarker:a study of current literature and systematic findings of ongoing clinical trials[J]. Immunol Res, 2023, 71(3):287-313. doi:10.1007/s12026-022-09352-2.
[11]	MARAKALA V. Neutrophil gelatinase-associated lipocalin (NGAL) in kidney injury - A systematic review[J]. Clin Chim Acta, 2022, 536:135-141. doi:10.1016/j.cca.2022.08.029.
[12]	SAĞLAM C, TURAN İ, ÖZAÇMAK H S. The effect of glucagon like peptide-1 receptor agonist on behavioral despair and anxiety-like behavior in ovariectomized rats: Modulation of BDNF/CREB,Nrf2 and lipocalin 2[J]. Behav Brain Res, 2022, 435:114053. doi:10.1016/j.bbr.2022.114053.
[13]	ARAOS P, AMADOR C A. Neutrophil gelatinase-associated lipocalin as an immunomodulator in endocrine hypertension[J]. Front Endocrinol(Lausanne), 2022, 13:1006790. doi:10.3389/fendo.2022.1006790.
[14]	SCHRÖDER S K, GASTERICH N, WEISKIRCHEN S, et al. Lipocalin 2 receptors:facts,fictions,and myths[J]. Front Immunol, 2023, 14:1229885. doi:10.3389/fimmu.2023.1229885.
[15]	ZHAO R Y, WEI P J, SUN X, et al. Role of lipocalin 2 in stroke[J]. Neurobiol Dis, 2023, 179:106044. doi:10.1016/j.nbd.2023.106044.
[16]	SHI C, WANG C, FU Z, et al. Lipocalin 2 (LCN2) confers acquired resistance to almonertinib in NSCLC through LCN2-MMP-9 signaling pathway[J]. Pharmacol Res, 2024, 201:107088. doi:10.1016/j.phrs.2024.107088.
[17]	DENG L, HE S, LI Y, et al. Identification of lipocalin 2 as a potential ferroptosis-related gene in ulcerative colitis[J]. Inflamm Bowel Dis, 2023, 29(9):1446-1457. doi:10.1093/ibd/izad050.
[18]	NAKAI M, MORIKAWA K, SASAKI T, et al. Neutrophil gelatinase-associated lipocalin predicts the efficacy of tolvaptan for ascites in patients with liver cirrhosis[J]. J Gastroenterol, 2023, 58(7):656-667. doi:10.1007/s00535-023-01993-w.
[19]	GUPTA U, GHOSH S, WALLACE C T, et al. Increased LCN2 (lipocalin 2) in the RPE decreases autophagy and activates inflammasome-ferroptosis processes in a mouse model of dry AMD[J]. Autophagy, 2023, 19(1):92-111. doi:10.1080/15548627.2022.2062887.
[20]	YAO F, DENG Y, ZHAO Y, et al. A targetable LIFR-NF-κB-LCN2 axis controls liver tumorigenesis and vulnerability to ferroptosis[J]. Nat Commun, 2021, 12(1):7333. doi:10.1038/s41467-021-27452-9.
[21]	KIM K E, LEE J, SHIN H J, et al. Lipocalin-2 activates hepatic stellate cells and promotes nonalcoholic steatohepatitis in high-fat diet-fed Ob/Ob mice[J]. Hepatology, 2023, 77(3):888-901. doi:10.1002/hep.32569.
[22]	WANG X, ZHANG C, ZOU N, et al. Lipocalin-2 silencing suppresses inflammation and oxidative stress of acute respiratory distress syndrome by ferroptosis via inhibition of MAPK/ERK pathway in neonatal mice[J]. Bioengineered, 2022, 13(1):508-520. doi:10.1080/21655979.2021.2009970.
[23]	HUANG Y, ZHANG N, XIE C, et al. Lipocalin-2 in neutrophils induces ferroptosis in septic cardiac dysfunction via increasing labile iron pool of cardiomyocytes[J]. Front Cardiovasc Med, 2022, 9:922534. doi:10.3389/fcvm.2022.922534.
[24]	LUO L, DENG L, CHEN Y, et al. Identification of lipocalin 2 as a ferroptosis-related key gene associated with hypoxic-ischemic brain damage via STAT3/NF-κB signaling pathway[J]. Antioxidants (Basel), 2023, 12(1):186. doi:10.3390/antiox12010186.
[25]	YADAV S K, ITO N, MINDUR J E, et al. Fecal Lcn-2 level is a sensitive biological indicator for gut dysbiosis and intestinal inflammation in multiple sclerosis[J]. Front Immunol, 2022, 13:1015372. doi:10.3389/fimmu.2022.1015372.
[26]	ZOLLNER A, SCHMIDERER A, REIDER S J, et al. Faecal biomarkers in inflammatory bowel diseases:calprotectin versus lipocalin-2-a comparative study[J]. J Crohns Colitis, 2021, 15(1):43-54. doi:10.1093/ecco-jcc/jjaa124.
[27]	THORSVIK S, DAMÅS J K, GRANLUND A V, et al. Fecal neutrophil gelatinase-associated lipocalin as a biomarker for inflammatory bowel disease[J]. J Gastroenterol Hepatol, 2017, 32(1):128-135. doi:10.1111/jgh.13598.
[28]	HSIEH H, MORIN J, FILLIETTAZ C, et al. Fecal Lipocalin-2 as a sensitive and noninvasive biomarker in the TNBS Crohn's inflammatory bowel disease model[J]. Toxicol Pathol, 2016, 44(8):1084-1094. doi:10.1177/0192623316665927.
[29]	KOMARU Y, OGUCHI M, SADAHIRO T, et al. Urinary neutrophil gelatinase-associated lipocalin and plasma IL-6 in discontinuation of continuous venovenous hemodiafiltration for severe acute kidney injury:a multicenter prospective observational study[J]. Ann Intensive Care, 2023, 13(1):42. doi:10.1186/s13613-023-01137-6.
[30]	MANFREDI M A, ZURAKOWSKI D, RUFO P A, et al. Increased incidence of urinary matrix metalloproteinases as predictors of disease in pediatric patients with inflammatory bowel disease[J]. Inflamm Bowel Dis, 2008, 14(8):1091-1096. doi:10.1002/ibd.20419.
[31]	BOLIGNANO D, DELLA TORRE A, LACQUANITI A, et al. Neutrophil gelatinase-associated lipocalin levels in patients with crohn disease undergoing treatment with infliximab[J]. J Investig Med, 2010, 58(3):569-571. doi:10.231/JIM.0b013e3181ccc20c.
[32]	JANAS R M, OCHOCIŃSKA A, SNITKO R, et al. Neutrophil gelatinase-associated lipocalin in blood in children with inflammatory bowel disease[J]. J Gastroenterol Hepatol, 2014, 29(11):1883-1889. doi:10.1111/jgh.12597.
[33]	KORKMAZ H, ASIL M, TEMEL T, et al. Evaluation of serum neutrophil gelatinase-associated lipocalin(NGAL),asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels,and their relations with disease type and activity in inflammatory bowel diseases[J]. Turk J Med Sci, 2021, 51(5):2403-2412. doi:10.3906/sag-2103-220.
[34]	STALLHOFER J, FRIEDRICH M, KONRAD-ZERNA A, et al. Lipocalin-2 is a disease activity marker in inflammatory bowel disease regulated by IL-17A,IL-22,and TNF-α and modulated by IL23R genotype status[J]. Inflamm Bowel Dis, 2015, 21(10):2327-2340. doi:10.1097/MIB.0000000000000515.
[35]	ANANTHAKRISHNAN A N, ADLER J, CHACHU K A, et al. AGA Clinical practice guideline on the role of biomarkers for the management of Crohn's disease[J]. Gastroenterology, 2023, 165(6):1367-1399. doi:10.1053/j.gastro.2023.09.029.
[36]	KOTLA N G, ROCHEV Y. IBD disease-modifying therapies:insights from emerging therapeutics[J]. Trends Mol Med, 2023, 29(3):241-253. doi:10.1016/j.molmed.2023.01.001.
[37]	ØSTVIK A E, GRANLUND A V, TORP S H, et al. Expression of Toll-like receptor-3 is enhanced in active inflammatory bowel disease and mediates the excessive release of lipocalin 2[J]. Clin Exp Immunol, 2013, 173(3):502-511. doi:10.1111/cei.12136.
[38]	KIM S L, SHIN M W, KIM S W. Lipocalin 2 activates the NLRP3 inflammasome via LPS-induced NF-κB signaling and plays a role as a pro-inflammatory regulator in murine macrophages[J]. Mol Med Rep, 2022, 26(6):358. doi:10.3892/mmr.2022.12875.
[39]	MAKHEZER N, BEN KHEMIS M, LIU D, et al. NOX1-derived ROS drive the expression of Lipocalin-2 in colonic epithelial cells in inflammatory conditions[J]. Mucosal Immunol, 2019, 12(1):117-131. doi:10.1038/s41385-018-0086-4.
[40]	KANG S B, KIM H, KIM S, et al. Potential oral microbial markers for differential diagnosis of Crohn's disease and ulcerative colitis using machine learning models[J]. Microorganisms, 2023, 11(7):1665. doi:10.3390/microorganisms11071665.
[41]	ELZAYAT H, MALIK T, AL-AWADHI H, et al. Deciphering salivary microbiome signature in Crohn's disease patients with different factors contributing to dysbiosis[J]. Sci Rep, 2023, 13(1):19198. doi:10.1038/s41598-023-46714-8.

作者	研究类型	参与机制	研究结论
Gupta等^[19]	基础研究	NF-κB/STAT1及细胞自噬	上调NGAL的表达可降低RPE细胞自噬，抑制NGAL表达可减少AMD的发生
Yao等^[20]	基础研究	LIFR/NK-κB/LCN2及铁死亡	抑制NK-κB调控的NGAL表达，调控铁死亡进展，改善肝癌病程
Kim等^[21]	基础研究	α-SMA/MMP9/STAT3	NGAL通过α-SMA/MMP9/STAT3信号通路，促进NASH进展
Wang等^[22]	基础研究	MAPK/ERK及铁死亡	抑制NGAL可干扰MAPK/ERK信号通路，减轻ARDS炎症反应和氧化应激损伤
Huang等^[23]	基础研究	铁死亡	NGAL诱导铁死亡，加重心功能障碍进展
Luo等^[24]	基础研究	NF-κB/STAT3及铁死亡	NGAL通过NF-κB/STAT3信号通路促进脑损伤神经元铁死亡
Yadav等^[25]	基础研究	NF-κB信号通路	促炎因子通过NF-κB诱导NGAL表达，NGAL是MS肠炎及菌群失调的标志物
Zollner等^[26]	病例对照研究	-	NGAL在CD中高表达，与FC、CRP、ESR呈显著正相关
Thorsvik等^[27]	病例对照研究	-	NGAL在CD中高表达，与FC、CRP、ESR呈显著正相关
Hsieh等^[28]	基础研究	-	粪便NGAL是小鼠CD模型的标志物
Komaru等^[29]	前瞻性研究	-	尿液NGAL是预测重症急性肾损伤的生物标志物
Manfredi等^[30]	前瞻性研究	-	MMP-9/NGAL是CD临床诊断的潜在标志物
Bolignano等^[31]	横断面研究	TNF-α介导Th1反应	IFX抑制TNF-α的表达，下调Th1介导的NGAL的产生
Janas等^[32]	病例对照研究	-	NGAL诱发肠道氧化应激反应，加重肠上皮损伤，且其水平与CD活动性呈正相关
Korkmaz等^[33]	病例对照研究	-	NGAL诱发肠道氧化应激反应，加重肠上皮损伤，且其水平与CD活动性呈正相关
Stallhofer等^[34]	病例对照研究	IL-23/Th17轴	炎性因子通过IL-23/Th17轴促进肠上皮细胞产生NGAL

作者	研究类型	参与机制	研究结论
Gupta等^[19]	基础研究	NF-κB/STAT1及细胞自噬	上调NGAL的表达可降低RPE细胞自噬，抑制NGAL表达可减少AMD的发生
Yao等^[20]	基础研究	LIFR/NK-κB/LCN2及铁死亡	抑制NK-κB调控的NGAL表达，调控铁死亡进展，改善肝癌病程
Kim等^[21]	基础研究	α-SMA/MMP9/STAT3	NGAL通过α-SMA/MMP9/STAT3信号通路，促进NASH进展
Wang等^[22]	基础研究	MAPK/ERK及铁死亡	抑制NGAL可干扰MAPK/ERK信号通路，减轻ARDS炎症反应和氧化应激损伤
Huang等^[23]	基础研究	铁死亡	NGAL诱导铁死亡，加重心功能障碍进展
Luo等^[24]	基础研究	NF-κB/STAT3及铁死亡	NGAL通过NF-κB/STAT3信号通路促进脑损伤神经元铁死亡
Yadav等^[25]	基础研究	NF-κB信号通路	促炎因子通过NF-κB诱导NGAL表达，NGAL是MS肠炎及菌群失调的标志物
Zollner等^[26]	病例对照研究	-	NGAL在CD中高表达，与FC、CRP、ESR呈显著正相关
Thorsvik等^[27]	病例对照研究	-	NGAL在CD中高表达，与FC、CRP、ESR呈显著正相关
Hsieh等^[28]	基础研究	-	粪便NGAL是小鼠CD模型的标志物
Komaru等^[29]	前瞻性研究	-	尿液NGAL是预测重症急性肾损伤的生物标志物
Manfredi等^[30]	前瞻性研究	-	MMP-9/NGAL是CD临床诊断的潜在标志物
Bolignano等^[31]	横断面研究	TNF-α介导Th1反应	IFX抑制TNF-α的表达，下调Th1介导的NGAL的产生
Janas等^[32]	病例对照研究	-	NGAL诱发肠道氧化应激反应，加重肠上皮损伤，且其水平与CD活动性呈正相关
Korkmaz等^[33]	病例对照研究	-	NGAL诱发肠道氧化应激反应，加重肠上皮损伤，且其水平与CD活动性呈正相关
Stallhofer等^[34]	病例对照研究	IL-23/Th17轴	炎性因子通过IL-23/Th17轴促进肠上皮细胞产生NGAL

中性粒细胞明胶酶相关脂质运载蛋白在克罗恩病临床诊断中的应用价值

Application value of neutrophil gelatinase associated lipocalin in clinical diagnosis of Crohn's disease

引用本文

RichHTML

PDF (PC)

可视化

摘要/Abstract

使用本文

图/表 1

参考文献 41

相关文章 15

编辑推荐

Metrics

本文评价

[1]	靳芳, 冯靖. 细胞学涂片在肺结节术中的快速病理诊断价值[J]. 天津医药, 2024, 52(9): 946-949.
[2]	王磊, 孟坤, 王兵. 支气管肺炎患儿反复喘息的影响因素分析及预测模型构建[J]. 天津医药, 2024, 52(8): 850-853.
[3]	金彩凤, 吴玮, 吴轲. B族链球菌感染及阴道微生态变化与不良妊娠结局的关系[J]. 天津医药, 2024, 52(8): 858-861.
[4]	李梦涛, 王迁. 结缔组织病相关间质性肺病：从发病机制研究到“双达标”治疗策略[J]. 天津医药, 2024, 52(7): 673-678.
[5]	邵红霞, 吴涓涓, 于洪志, 吴琦, 武俊平. 血行播散性肺结核合并颅内结核的临床特点[J]. 天津医药, 2024, 52(5): 495-498.
[6]	付秀娟, 卢祖能. 糖尿病合并慢性炎性脱髓鞘性多发性神经根神经病研究进展[J]. 天津医药, 2024, 52(2): 220-224.
[7]	周秀芬, 刘晖, 陈虹, 赵宗波. SAP患者GLI与外周血各指标变化的临床意义[J]. 天津医药, 2024, 52(12): 1286-1291.
[8]	陆艺蓓, 金冬霞, 宋振春, 马昊原, 李彦, 郝天旭, 李曦铭. 新型柔性贴片式心电仪的临床应用[J]. 天津医药, 2024, 52(10): 1095-1099.
[9]	冯连云, 田晶, 王光霞, 刘甚佳, 王红, 庞丽娜. 超声造影在肾透明细胞癌与尿路上皮癌鉴别诊断中的价值[J]. 天津医药, 2023, 51(5): 540-543.
[10]	滕丽峰, 陈茜茜, 叶丛, 黄玉冰. 血清Sestrin2在急性ST段抬高型心肌梗死中的表达及其与缺血再灌注损伤的关系[J]. 天津医药, 2023, 51(3): 303-306.
[11]	许莉敏, 谢燕. 外周血单核细胞DNMT1及血清IL-6在糖尿病肾脏病中的表达及意义[J]. 天津医药, 2023, 51(2): 194-197.
[12]	陈俊, 郑锦豪, 陈家良, 陈博. 阿尔茨海默病患者血清GGT、CTHRC1表达水平检测及临床意义[J]. 天津医药, 2023, 51(2): 216-220.
[13]	邢建男, 何伟. 干眼的影响因素及其临床诊断价值探讨[J]. 天津医药, 2023, 51(1): 100-104.
[14]	张宇, 刘梁生, 马文娟, 韩敏, 朱鹰, 路红. 早期肿块型乳腺浸润性导管癌超声征象与分子分型的相关性研究[J]. 天津医药, 2022, 50(8): 853-858.
[15]	刘逸翔, 范文俊, 丁振江, 张英, 史菲, 刘静怡, 孙瓅贤. WMR、MLR及两者联合对冠心病及冠状动脉病变严重程度的诊断价值[J]. 天津医药, 2022, 50(8): 859-862.