妊娠糖尿病患者血清中性粒细胞明胶酶相关脂质运载蛋白水平变化

目的:探讨糖代谢异常孕妇血清中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平变化的临床意义。方法:74例糖代谢异常孕妇及66例正常孕妇(NGT组)纳入研究。根据糖耐量试验(OGTT)将糖代谢异常孕妇分为妊娠期糖尿病组(GDM组,n=26)和妊娠期糖耐量受损组(GIGT组,n=48)。测定三组空腹血糖(FBG)、胰岛素(FINS)、NGAL及肿瘤坏死因子-α(TNF-α)浓度,计算胰岛素抵抗指数(HOMA-IR),并比较三组妊娠结局。结果:GDM组FBG、HOMA-IR、FINS、NGAL及TNF-α较GIGT组和NGT组显著升高(P<0.01);GIGT组仅HOMA-IR及NGAL高于NGT组(P<0.05)。所有患者血清NGAL与HOMA-IR呈显著正相关(r=0.886,P<0.01);GDM组血清NGAL还与FINS、TNF-α呈显著正相关(r=0.874,r=0.867,P均<0.01)。GDM组妊娠结局较GIGT组和NGT组差。结论:NGAL可能是一个敏感的GDM诊断指标;妊娠糖尿病中的高胰岛素抵抗状态可能是引起NGAL升高的因素。     

糖尿病肾病患者血清中性粒细胞明胶酶相关脂质运载蛋白的改变及其临床意义

目的:探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在2型糖尿病(T2DM)并发肾病患者血清中的表达及临床价值。方法:90例T2DM和30例健康查体者为研究对象,90例T2DM患者根据24 h尿白蛋白水平分为4组:A组,正常蛋白尿组(24 h尿蛋白排泄量(uAlb)30 mg);B组,微量白蛋白尿组(24 h uAlb 30～300 mg);C组:大量白蛋白尿组(24 h uAlb300 mg)。测定血清NGAL水平、肾小球滤过率(GFR)、血肌酐(Scr)水平,常规检测血脂水平。结果:T2DM组血清NGAL水平和GFR与对照组比较显著下降(P0.05),TG、Scr与对照组比较显著上升;血清NGAL、TG水平和GFR为A组B组C组,三组间比较有显著性差异(P0.05);血清Scr水平为A组B组C组,三组间比较有统计学差异(P0.05)。T2DM患者血清NGAL水平与GFR、TG水平呈显著正相关(r=0.612,0.4510;P0.05);血清NGAL水平与血清Scr水平呈显著负相关(r=-0.4120,P0.05)。结论:T2DM并发肾损伤患者血清NGAL水平明显降低,且与肾损伤程度相关,因此,NGAL可以做为判定T2DM并发肾损伤的可靠指标。     

中性粒细胞明胶酶相关脂质运载蛋白在急性肾损伤早期诊断及治疗中作用的研究进展

急性肾损伤是临床常见疾病,但早期诊断缺乏敏感性、特异性好的标志物.中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)作为急性肾损伤早期诊断的指标越来越受到关注,研究发现NGAL可用来预测急性肾损伤严重程度及判断预后,重组NGAL甚至对肾小管具有保护作用.本文就NGAL在急性肾损伤诊断及治疗中的研究作一综述.     

心衰患儿血浆中性粒细胞明胶酶相关载脂蛋白的表达及临床意义

目的中性粒细胞明胶酶相关载脂蛋白(NGAL)在临床上被广泛应用于肾脏疾病的诊断,而与小儿心衰的关系很少被研究。本文旨在探讨心衰患儿血浆NGAL表达水平及临床意义。方法选取40例心衰患儿作为实验组,按照纽约心脏学会(NYHA)分类法进行心功能分级。另选取年龄、性别相匹配的40例健康体检者作为对照组。记录两组患者血浆NGAL与N-末端B型脑钠肽前体(NT-proBNP)水平以及左心功能指标左心室射血分数(LVEF),比较实验组不同心衰等级患儿血浆NGAL水平。结果实验组心衰患儿血浆NGAL及NT-proBNP水平均明显高于对照组,而LVEF显著低于对照组;血浆NGAL与NT-proBNP呈正相关(r=0.76,P0.05),与LVEF呈负相关(r=-0.37,P0.05);不同等级心衰患儿血清肌酐和血红蛋白水平比较,差异无统计学意义。结论心衰患儿血浆NGAL水平显著升高,且与心衰严重程度呈正相关,检测血浆NGAL水平对小儿心衰的诊断和预后评估具有重要的临床应用价值。     

尿NGAL在IgA肾病肾小管间质损伤评估中的意义探讨

目的 探讨尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在IgA肾病(IgAN)患者肾小管间质损伤(TIL)评估中的意义.方法 应用酶联免疫法(ELISA)检测110例IgAN患者,30例非IgAN肾小球疾病患者以及30例健康对照者的尿NGAL水平.结果 IgAN组、非IgAN疾病对照组较健康对照组尿NGAL水平均明显升高(P＜0.01);IgAN组尿NGAL水平与多项临床病理指标明显相关;影响尿NGAL水平的独立影响因素有血白蛋白水平,尿蛋白定量、尿NAG酶、尿渗透压,以及球性硬化、间质炎细胞浸润、间质纤维化、肾小管萎缩;以尿NGAL水平超过正常对照组2个标准差视为显著增高,联合NAG酶对有无TIL进行评估,ROC曲线下面积为0.850,明显优于血肌酐的0.675,灵敏度83.3％,特异度73.3％,准确率81.2％.结论 IgAN患者尿NGAL水平可以反映IgAN病情程度,在联合尿NGAL与尿NAG酶判别有无TIL时明显优于血肌酐及单纯的尿NGAL、尿NAG酶、尿渗透压等指标.     

高血压肾病早期血尿NGAL水平的变化及临床意义

目的:研究高血压肾病早期血尿NGAL(中性粒细胞明胶酶相关脂质运载蛋白)水平的变化及其临床意义。方法:选取90例原发性高血压患者按24 h尿微量白蛋白排泄率(Urinary microalbumin excreting rate,UAER)分为正常蛋白尿组(A组,30例,UAER<30 mg/24 h),微量蛋白尿组(B组,30例,UAER介于30~300 mg/24 h)及大量蛋白尿组(C组,30例,UAER>300 mg/24 h);30例健康体检人员(D组)。检测各组患者血、尿NGAL含量,血肌酐(Serum creatinine,Scr)、尿素氮(Blood urea nitrogen,BUN)、半胱氨酸蛋白酶抑制剂C(Cystatin C,Cys C)、超敏C反应蛋白(High sensitive C reactive protein,hs CRP)、尿转铁蛋白(Transferrin,TF)含量及清晨基础血压(Blood pressure,BP)。1年后随访同一批患者,再次检测上述各指标,比较随访前后各指标的改变,分析血、尿NGAL的相互关系,同时分析二者与其他各指标的相互关系。结果:90例原发性高血压肾病患者中微量蛋白尿组与大量蛋白尿组血清NGAL与GFR水平较正常对照组明显下降,尿NGAL较正常对照组明显升高,差异有统计学意义(P<0.05)。30例正常蛋白尿组与正常对照组比较未见明显异常。结论:血尿NGAL水平在高血压肾病早期较正常对照组已有明显趋势性变化,可作为其早期肾脏并发症的可靠指标。     

原发性肾病综合征并发急性肾损伤患者血清及肾组织中NGAL的表达及意义

 目的：检测原发性肾病综合征（PNS）患者血清及肾组织中中性粒细胞明胶酶相关脂质运载蛋白（NGAL）的水平,探讨PNS合并急性肾损伤（AKI）时患者血清及肾组织中NGAL浓度的变化。方法：72例PNS患者根据病理结果分为：(1) PNS合并急性肾小管坏死（ATN）组15例,其中微小病变（MCD）合并ATN 10例,系膜增生（MsPGN）合并ATN 5例;(2) PNS不合并ATN组57例,其中MCD组24例,膜性肾病（MN）组23例和MsPGN组10例。15例健康体检者的血液及5例正常肾组织作为正常对照组。采用ELISA检测血清NGAL的水平;采用免疫组化法检测肾组织中NGAL的表达。结果：(1) PNS患者血清NGAL水平及肾组织中NGAL表达明显高于正常对照组（P<0.05）,其中MN组较MCD组和MsPGN组血清NGAL水平明显升高（P<0.05）。(2) MCD合并ATN组和MsPGN合并ATN组血清NGAL水平及肾组织中NGAL表达较不合并ATN组显著升高（P<0.05）。(3)血清中NGAL与24 h尿蛋白定量、血尿素氮和血肌酐呈正相关（P<0.05）,与血清白蛋白和β2微球蛋白无明显相关性（P>0.05）;血清中NGAL与肾组织NGAL的表达呈正相关（P<0.01）。结论：血清NGAL可能作为判断原发性肾病综合征并发急性肾损伤的早期、无创、敏感指标。     

乳腺癌患者肿瘤细胞NGAL水平免疫组织化学测定的临床意义

目的：探讨浸润性乳腺癌组织中性粒细胞明胶酶相关脂质运载蛋白（neutrophil gelatinase-associatedlipocalin,NGAL）表达水平测定的临床意义。方法：60例乳腺癌患者及52例乳腺增生症患者分成两组,肿瘤细胞NGAL水平用免疫组化法检测并作分析。结果：①浸润性乳腺癌组织中的NGAL阳性表达率明显高于乳腺增生症;且前者为强阳性表达,后者阳性程度明显呈弱势,为阳性或弱阳性表达,阳性表达率分别为78.33.%和17.30%,两组之间阳性表达率比较存在显著性统计学差异（χ2=54.648,P〈0.05）。②浸润性乳腺癌组织NGAL阳性表达率与病理进展关系统计数据显示,肿瘤直径〈2cm与〉2cm两组比较,NGAL阳性表达率无显著差异（χ2=2.103,P〉0.05）;有淋巴结转移组与无淋巴结转移组间比较NGAL阳性表达率差异有显著性（χ2=9.105,P〈0.05）,Ⅰ-Ⅱ级与Ⅲ-Ⅳ级组间阳性表达率差异也有显著性（χ2=11.211,P〈0.05）。结论：浸润性乳腺癌组织中的NGAL阳性表达率与肿瘤直径大小关系不大,而与肿瘤的转移与否和分级呈平行相关。     

联合检测B型尿钠肽、中性粒细胞明胶酶相关载脂蛋白和肾小球滤过率在心力衰竭合并肾功能不全患者诊治中的应用

目的研究血清中B型尿钠肽(B type natriuretic peptide,BNP)和中性粒细胞明胶酶相关载脂蛋白(neutrophil gelatinase-associated lipocalin,NGAL)的表达水平和肾小球滤过率(glomerular filtration rate,GFR)在心力衰竭合并肾功能不全患者诊治中的作用。方法回顾性研究分析我院2014年3月至2015年3月收治的心肾综合征患者共63例。根据临床表现将患者分为观察组(心力衰竭合并肾功能不全患者)与对照组(单纯心力衰竭患者),其中观察组根据纽约心脏病学协会(NYHA)标准对心功能进一步分级为NYHA II,NYHA III和NYHA IV三组,分别检测各样本血清中BNP、NGAL的表达水平和估算GFR水平,进行医学统计分析并比较各组之间差异是否具有统计学意义。结果对照组与观察组间患者年龄差异具有统计学意义,观察组冠心病患者比例明显高于对照组。观察组中不同心功能分级患者血清BNP水平和NGAL水平均显著高于对照组,GFR水平均显著低于对照组;BNP、NGAL水平在观察组中不同心功能分级患者血清中差异具有统计学意义且呈正相关性;GFR在观察组中不同心功能分级患者中差异具有统计学意义且呈负相关;且BNP、NGAL与GFR具有显著负关联性。结论联合检测BNP、NGAL在血清中表达水平和评估GFR水平可以为预测心力衰竭患者合并肾功能不全的发生和程度提供有效依据,并且该联合检测具有高敏感度,高特异性,检测快速等优点。     

Clinical application of neutrophil gelatinase-associated lipocalin in the revised chronic kidney disease classification

Background: A revised classification of chronic kidney disease (CKD) was proposed by the Kidney Disease: Improving Global Outcomes (KDIGO) in 2012. Neutrophil gelatinase-associated lipocalin (NGAL) was considered as one of the most promising biomarkers in clinical nephrology. The aim of this study was to examine the level of NGAL in patients with different impairment of GFR based on the new classification, and to evaluate whether NGAL in serum or urine was associated with different risk categories in CKD patients. Methods: A cross-sectional study was performed in 240 patients with CKD. NGAL, serum cystatin C, β₂-macroglobulin (β₂-MG), urine α₁-macroglobulin (α₁-MG) and albuminuria were tested in patients with various degrees of renal impairment. Results: Good correlation was found between the NGAL and the cystatin C, β₂-MG and the α₁-MG (r > 0.7). The level of sNGAL in CKD stage 3b was more than that in CKD stage 3a (P = 0.025). The concentration of the NGAL increased progressively with the increasing of risk categories (proposed by the revised CKD classification). The cutoff value of NGAL was calculated from stage 2 to stage 5. ROC analysis showed good AUC (sNGAL > 0.8, uNGAL > 0.7) and high specificity (sNGAL > 87%, uNGAL > 90%) on the cutoff value of NGAL. Conclusion: The results confirm NGAL as a useful biomarker in clinical nephrology which is helpful to diagnosis and evaluate the categories for CKD proposed by the KDIGO.     

Involvement of neutrophil gelatinase-associated lipocalin and osteopontin in renal tubular regeneration and interstitial fibrosis after cisplatin-induced renal failure

The kidney has a capacity to recover from ischemic or toxic insults that result in cell death, and timely tissue repair of affected renal tubules may arrest progression of injury, leading to regression of injury and paving the way for recovery. To investigate the roles of neutrophil gelatinase-associated lipocalin (NGAL/lcn2) and osteopontin (OPN/spp1) during renal regeneration, the expression patterns of NGAL and OPN in the cisplatin-induced rat renal failure model were examined. NGAL expression was increased from day 1 after injection; it was seen mainly in the completely regenerating proximal tubules of the cortico-medullary junction on days 3–35; however, the expression was not seen in abnormally dilated or atrophied renal tubules surrounded by fibrotic lesions. On the other hand, OPN expression was increased from day 5 and the increased expression developed exclusively in the abnormal renal tubules. NGAL expression level well correlated with the proliferating activity in the regenerating renal epithelial cells, whereas OPN significantly correlated with the α-smooth muscle actin-positive myofibroblast appearance, expression of transforming growth factor (TGF)-β1, and the number of CD68-positive macrophages. Interestingly, rat renal epithelial cell line (NRK-52E) treated with TGF-β1 decreased NGAL expression, but increased OPN expression in a dose-dependent manner. Because increases of TGF-β1, myofibroblasts and macrophages contribute to progressive interstitial renal fibrosis, OPN may be involved in the pathogenesis of fibrosis; on the contrary, NGAL may play a role in tubular regeneration after injury. Expression analysis of NGAL and OPN would be useful to investigate the tubule damage in renal-toxicity.     

Plasma neutrophil gelatinase-associated lipocalin as an early biomarker for prediction of acute kidney injury after cardio-pulmonary bypass in pediatric cardiac surgery

Introduction

Cardiopulmonary bypass (CPB) surgery is considered one of the most frequent surgical procedures in which acute kidney injury (AKI) represents a frequent and serious complication. The aim of the present study was to evaluate the efficiency of neutrophil gelatinase-associated lipocalin (NGAL) as an early AKI biomarker after CPB in pediatric cardiac surgery.

Material and methods

The study included forty children aged 2 to 78 months undergoing CPB. They were divided into group I: patients who suffered AKI grades II and III; and group II: patients who did not develop AKI or at risk. Peripheral venous blood was withdrawn pre- and post-operatively for serial measurements of NGAL and creatinine. Statistical analysis was performed using Statistical Package for Social Sciences version 14.

Results

Mean plasma NGAL levels showed highly significant elevations in group I patients at 2, 12, and 24 h after surgery (p < 0.0001) compared to group II. Significant correlations were found between NGAL and creatinine at different time intervals. Highly significant correlations (p < 0.0001) were found between plasma NGAL and AKI at 2, 12 and 24 h after surgery. A cut-off level of 100 ng/ml at 2 h, and 125 ng/ml at 12 h post-operatively both recorded the highest accuracy, being 95% accurate, with sensitivity of 100% and 89.5% respectively, and specificity of 90.5% and 100% respectively.

Conclusions

This study showed that plasma NGAL could be used as an early biomarker for detection of AKI following CPB. We recommend further studies on a wider scale to validate the current study results.     

中性粒细胞胞外诱捕网在新生大鼠急性肺损伤中的作用

目的:探讨中性粒细胞胞外诱捕网(NETs)在新生大鼠急性肺损伤(ALI)中的作用。方法:取出生7 d的SD大鼠30只,按照随机数字表法分成生理盐水对照组、ALI组及ALI+脱氧核糖核酸酶(Dnase)组,每组10只。ALI组用脂多糖(LPS)以20 mg/kg的剂量腹腔注射,ALI+Dnase组则在注射LPS后即腹腔注射Dnase(5 mg/kg)。给药6 h后,水合氯醛麻醉大鼠,收集支气管肺泡灌洗液(BALF),荧光酶标仪检测BALF中游离DNA(cf-DNA)的含量;右肺组织固定于4%多聚甲醛中,HE染色观察各组大鼠肺组织形态结构;左肺组织制备肺组织匀浆,酶联免疫吸附测定(ELISA)法检测肺组织匀浆中白细胞介素6(IL-6)及肿瘤坏死因子α(TNF-α)的含量;使用免疫荧光法与Western blot检测各组大鼠肺组织中瓜氨酸化组蛋白H3(CitH3)及髓过氧化物酶(MPO)的生成情况。结果:与对照组相比,ALI组与ALI+Dnase组中cf-DNA、CitH3、MPO、IL-6及TNF-α水平均升高(P<0.05),肺组织中炎性细胞浸润严重;与ALI组相比,ALI+Dnase组新生大鼠肺组织中cf-DNA、Cith3、MPO、IL-6及TNF-α水平降低(P<0.05),ALI+Dnase组炎症浸润程度降低。结论:新生大鼠ALI中,NETs水平为反映肺组织损伤的重要指标,NETs可能为治疗新生儿ALI的新靶点。     

Urinary neutrophil gelatinase-associated lipocalin in critically ill surgical cancer patients

Background and Aims:

Neutrophil gelatinase-associated lipocalin (N-GAL) is an early biomarker of acute kidney injury (AKI) due to various etiologies. On the other hand, N-GAL is also elevated in patients with acute inflammatory conditions and in several solid neoplasms. The goal of this study was to assess the efficacy of N-GAL as a predictor of AKI and mortality in oncological surgical patients postoperatively in the intensive care unit (ICU).

Methods:

This was a prospective cohort observation study on adult cancer patients submitted to elective or emergency surgeries and admitted in the ICU. Urinary N-GAL was measured at the first 2 h after admission. AKI incidence and other complications were assessed, including hospital mortality.

Results:

A total of 22 patients were assessed (77% male, age 52.8 years, Acute Physiology and Chronic Health Evaluation II [APACHE II] 17.3) in whom the most frequent site of cancer was the gastrointestinal tract. AKI incidence was 13.6%. Urinary N-GAL was a predictor of AKI (22.0 ng/ml in patients without AKI vs. 239.1 ng/ml in patients with AKI, P < 0.001). Multivariate analysis showed that the main predictors of AKI were age, APACHE II, and N-GAL. N-GAL was also higher, although not statistically significant in patients who died in the hospital.

Conclusions:

In oncological postoperative patients admitted to the ICU, urinary N-GAL was an independent predictor of AKI; moreover, its level was higher in the deceased patients.     

呼吸机相关性肺损伤的炎症反应机制

机械通气是治疗急性呼吸窘迫综合征的主要手段，但呼吸机应用不当也可能加重原有的肺损伤，引起呼吸机相关性肺损伤。呼吸机相关性肺损伤本质上是生物伤，异常的机械力作用于细胞，激活细胞内信号转导通路，活化炎性细胞，产生大量炎症介质，加重炎症反应。探讨呼吸机相关性肺损伤的炎症反应机制，阻断机械力作用向细胞内的传导和细胞内信号转导途径的激活，减少炎症细胞的激活和炎症介质基因的表达，对于预防呼吸机相关性肺损伤发挥重要作用。     

丙泊酚对呼吸机所致肺损伤大鼠的保护作用及机制

目的探索丙泊酚对呼吸机所致肺损伤(VILI)模型大鼠的保护作用,并分析其调控机制。方法利用大潮气量通气建立肺损伤模型,将30只SD大鼠随机分为假手术组、模型组和丙泊酚组,每组10只。检测大鼠肺组织湿/干重比(W/D)、大鼠肺组织形态学变化情况、大鼠肺组织中TNF-α和IL-6含量以及JAK、STAT3 mRNA和蛋白水平,并比较3组大鼠肺组织中SOD、MDA的含量。结果与假手术组相比,模型组W/D明显较高,肺组织病理学形态较差,肺组织中TNF-α和IL-6含量明显较高,JAK、STAT3 mRNA水平较高,p-JAK、p-STAT3蛋白水平较高,MDA的含量较高,而SOD的含量较低,以上差异均有统计学意义(P<0.05);与模型组相比,丙泊酚组W/D明显较低,肺组织形态学得到改善,肺组织中TNF-α和IL-6含量明显较低,JAK、STAT3 mRNA水平较低,p-JAK、p-STAT3蛋白水平较低,MDA的含量较低,SOD的含量较高,以上差异均有统计学意义(P<0.05)。结论丙泊酚对VILI模型大鼠具有减弱炎症反应的作用,其机制可能与抑制JAK/STAT3信号通路有关。     

丙泊酚对呼吸机所致肺损伤大鼠的保护作用及其机制

目的探讨p38信号通路在丙泊酚抑制呼吸机所致肺损伤（VILI）大鼠肺组织表达高迁移率族蛋白B1（HMGB1）中的作用。方法将32只健康SD大鼠随机分为4组,每组8只。对照组（A组）不行机械通气,保留自主呼吸;常规通气组（B组）潮气量（VT）为8ml/kg;大潮气量通气组（C组）VT为30ml/kg;大潮气量通气＋丙泊酚组（D组）VT为30ml/kg,同时静脉注射丙泊酚8mg/（kg.h）。机械通气4h后处死动物,测定支气管肺泡灌洗液（BALF）中总蛋白水平、白细胞计数以及肺湿干重比值（W/D）和中性粒细胞髓过氧化物酶（MPO）活性。采用Western blot方法检测肺组织HMGB1蛋白含量以及p38的激酶活性,采用RT-PCR方法检测HMGB1 mRNA的表达。应用单因素方差分析进行不同组别间的比较。结果通气4h后,与A组相比,C组总蛋白水平（1.58±0.46）g/L、白细胞计数（112.05±21.33）×107/L、肺W/D比值（8.25±0.92）、MPO活性（3.08±0.85）U/g、HMGB1蛋白（0.43±0.13）和mRNA（0.30±0.08）表达以及p38激酶活性（0.52±0.11）均明显增加（P〈0.05）;与C组相比,D组上述各项指标的变化均明显降低（P〈0.05）。结论丙泊酚可改善VILI肺内炎症反应,可能与通过p38信号通路抑制HMGB1蛋白和mRNA的表达有关。