Serum Neutrophil Gelatinase-associated Lipocalin(NGAL)Is Elevated in Patients with Asthma and Airway Obstruction

Neutrophilic airway inflammation is one of the features of severe asthma.Neutrophil gelatinase-associated lipocalin(NGAL),or lipocalin-2,is a glycoprotein associated with neutrophilic inflammation and can be detected in blood.Recently,blood NGAL levels have been reported to be elevated in chronic obstructive pulmonary disease.However,the clinical significance of serum NGAL levels in patients with asthma has not been elucidated.The aim of this study was to explore the association between serum NGAL level and clinical parameters in patients with asthma.Sixty.one non-smoking people with stable asthma were enrolled in this study.All patients underwent blood ollction and pulmonary function tests.The associations between serum NGAL levels and clinical parameters were analyzed retrospectively.Serum NGAL levels in patients with asthma and obstructive ventilatory defect were higher than those in patients with asthma without obstructive ventilatory defect(76.4±51.4 ng/mL vs.39.3±27.4 ng/mL,P=0.0019).Serum NGAL levels were correlated with forced expired flow at 50%of vital capacity%predicted and forced expired flow at 75%of vital capacity%predicted(r=-0.3373,P=0.0078 and r=0.2900,P=0.0234,respectively).Results of a multiple regression analysis demonstrated that serum NGAL level was independently associated with obstructive ventilatory defect.Serum NGAL levels were elevated in patients with asthma and obstructive ventilatory defect.NGAL may be involved in airway remodeling possibly mediated by neutrophilic inflammation in asthma.

Neutrophil gelatinase-associated lipocalin does not predict acute kidney injury in heart failure

BACKGROUND Acute cardiorenal syndrome type 1(CRS-1)is defined by a rapid cardiac dysfunction leading to acute kidney injury(AKI).Neutrophil gelatinaseassociated lipocalin(NGAL)is expressed on the surface of human neutrophils and epithelial cells,such as renal tubule cells,and its serum(sNGAL)and urinary have been used to predict AKI in different clinical settings.AIM To characterize CRS-1 in a cohort of patients with acute heart diseases,evaluating the potentiality of sNGAL as an early marker of CRS-1.METHODS We performed a retrospective cohort,multi-centre study.From January 2010 to December 2011,we recruited 202 adult patients admitted to the coronary intensive care unit(CICU)with a diagnosis of acute heart failure or acute coronary syndrome.We monitored the renal function to evaluate CRS-1 development and measured sNGAL levels within 24 h and after 72 h of CICU admission.RESULTS Overall,enrolled patients were hemodynamically stable with a mean arterial pressure of 92(82-107)mmHg,55/202(27.2%)of the patients developed CRS-1,but none of them required dialysis.Neither the NGAL delta value(AUC 0.40,95%CI:0.25-0.55)nor the NGAL peak(AUC 0.45,95%CI:0.36-0.54)or NGAL cutoff(≥140 ng/mL)values were statistically significant between the two groups(CRS-1 vs no-CRS1 patients).The area under the ROC curve for the prediction of CRS-1 was 0.40(95%CI:0.25-0.55)for the delta NGAL value and 0.45(95%CI:0.36-0.54)for the NGAL peak value.Finally,in multivariate analysis,the risk of developing CRS-1 was correlated with age>60 years,urea nitrogen at admission and 24 h-urine output(AUC 0.83,SE=60.5%SP=93%),while sNGAL was not significantly correlated.CONCLUSION In our population,sNGAL does not predict CRS-1,probably as a consequence of the mild renal injury and the low severity of heart disease.So,these data might suggest that patient selection should be taken into account when considering the utility of NGAL measurement as a biomarker of kidney damage.

Combination of neutrophil gelatinase-associated lipocalin and matrix metalloproteinase-9 are biomarkers for the detection of colon tubular adenocarcinoma

BACKGROUND Tubular adenocarcinoma of the colon,which originates from the epithelium of the glands,is a major health concern worldwide.However,it is difficult to detect at an early stage.The lack of biomarkers is a main barrier to the diagnosis and treatment of tubular adenocarcinoma.Neutrophil gelatinase-associated lipocalin(NGAL)is a secreted protein that induces the expression of matrix metalloproteinase-9(MMP-9)and is involved in various tumors.NGAL and MMP-9 have been reported to be associated with tumorigenesis and development.They may have potential as biomarkers for diagnosis of tubular adenocarcinoma of the colon.AIM To determine whether NGAL and MMP-9 can be used as potential biomarkers to indicate the progression of tubular adenocarcinoma of the colon.METHODS Samples were collected from surgically excised tissue from various patients.The content of pro-gastrin-releasing peptide(pro-GRP)in the serum was measured by an electrochemiluminescence immunoassay.The expression patterns of NGAL and MMP-9 and the relationship between NGAL and MMP-9 were examined by quantitative real-time PCR,Western blotting and immunohistochemical analysis.RESULTS In this study,we found that NGAL and MMP-9 can be used as biomarkers for the detection of tubular adenocarcinoma of the colon and that their combination improved diagnostic accuracy.By analyzing the expression of NGAL in tubular adenocarcinoma at different levels,we found that NGAL expression was significantly upregulated in primary tubular adenocarcinoma tissues compared with normal tissues.The upregulation of NGAL expression was strongly correlated with both the degree of differentiation and the disease stage(I–III),indicating that NGAL could serve as a diagnostic biomarker for tubular adenocarcinoma.When using NGAL as a biomarker for diagnosis,the accuracy was similar to that achieved with the widely used biomarker pro-GRP,suggesting that NGAL is reliable.Moreover,the expression of MMP-9 was also strongly correlated with the differentiation stage,demonstrating that MMP-9 could be used as a biomarker to indicate the progression of tubular adenocarcinoma of the colon.More importantly,the combination of NGAL and MMP-9 produced a more accurate diagnosis of tubular adenocarcinoma,and these results were further confirmed by immunohistochemical analysis of tissue sections.CONCLUSION Our study demonstrated that both NGAL and MMP-9 can be used as biomarkers for the diagnosis of colon tubular adenocarcinoma and that the results could be further improved by combining them.

The Differences of Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL) Levels between Asphyxiated and Non-Asphyxiated Neonates

Objective: To evaluate the differences of urinary NGAL levels between asphyxiated and non-as- phyxiated neonates. Methods: This was a cross-sectional observational analytic study, including 34 newborns in Dr. Hasan Sadikin Hospital, Bandung, Indonesia. Sample collection was conducted from December 2014 to March 2015. Urine NGAL levels were evaluated using enzyme-linked immunosorbent assays (ELISA) technique. To determine the differences of urinary NGAL levels between asphyxiated and non-asphyxiated group we used Mann-Whitney U test, and to determine the differences of gestational age and birth weight between these two groups we used Fisher’s exact test. Results: Twenty males (60%) and 14 females (40%) neonates participated in the study. From 34 subjects, 17 neonates were diagnosed with asphyxia and 17 neonates without asphyxia. The results showed that urine NGAL levels had significantly increased in asphyxiated neonates. The median urine NGAL level in asphyxiated group is 95% CI: 506.7 (60.0 - 651.7) ng/mL, while the median urine NGAL level in non-asphyxiated group is 95% CI: 6.7 (0.1 - 53.0) ng/mL. Statistically, there were significant urine NGAL levels differences between asphyxiated and non-asphyxi- ated neonates (p < 0.001). There were no differences in gestational age and birth weight between asphyxiated and non-asphyxiated neonates (p > 0.05). Conclusions: Urinary NGAL levels in asphyxiated neonates were significantly higher than those in non-asphyxiated neonates. There were significant differences of urine NGAL levels between the groups.

Evaluation of Reticulocyte Hemoglobin Content and Serum Neutrophil Gelatinase-Associated Lipocalin as Predictive Biomarkers of Anemia in Children on Hemodialysis

Background: Diagnosis of iron deficiency anemia with currently available tests is rendered difficult in hemodialysis patients. The aim: To investigate the role of reticulocyte Hemoglobin Content (CHr) in the diagnosis of iron deficiency anemia in hemodialysis children in comparison to the used traditional markers and assess the impressiveness and the utility of Neutrophil Gelatinase Associated Lipocalin (NGAL) as a novel biomarker of iron status in those patients. Methods: This study investigated CHr in addition to NGAL serum level in the same line with traditional markers for anemia, including: CBC, serum iron, ferritin, total iron-binding capacity (TIBC), and transferrin saturation (TSAT%). Results: It is more significant that CHr content in hemodialysis children is lower than their controls as they are (27.06 ± 2.90) pg and (32.86 ± 3.59) pg, respectively, p = 0.01. There is no significant difference regarding NGAL between the study groups. Significant negative correlation between CHr with ferritin, urea, creatinine, and positively correlated with iron and RBCS. CHr showed a sensitivity of 90% and specificity of 86.67% to detect iron-deficiency anemia with a cut-off value of 27 pg. Conclusion: CHr is superior to ferritin and TSAT % for the early diagnosis of iron deficiency anemia in hemodialysis children;our results do not support NGAL as a marker of anemia in hemodialysis patients.

Correlation between Serum Neutrophil Gelatinase Associated Lipocalin and Burn Severity: A Pilot Study

The severity of an initial burn injury is critical for determining the treatment plan and prognosis of burn patients. Here, we measured serum neutrophil gelatinase-associated lipocalin (NGAL) levels to determine whether NGAL can be used as a biomarker for severity of burn injuries. A study of the demographic, clinical, and laboratory markers for various organ damage was performed at Bestian Burn Center (n = 10 healthy people, n = 31 patients). NGAL and organ damage marker levels were measured in 31 patients with severe burns within 2 - 3 days following their admission to the intensive care unit. Serum NGAL level of the expired patients was 788.5 (685.0 - 998.0) pg/mL, whereas that of the discharged patients was 421.2 (356.2 - 480.6) pg/mL, showing that the initial serum NGAL level can be used to estimate mortality. We also determined the correlation between serum NGAL level and the currently used severity markers (total body surface area burned and abbreviated burn severity index) and confirmed that serum NGAL level could be used as a severity marker. We also found that serum NGAL level was correlated with damage of organs such as the liver, kidney, heart, and respiratory organs in patients with severe burns.

Plasma neutrophil-gelatinase-associated lipocalin and cystatin C could early diagnose contrast-induced acute kidney injury in patients with renal insufficiency undergoing an elective percutaneous coronary intervention

Background Contrast induced acute kidney injury （CIAKI） is an important complication in the use of iodinated contrast media （CM）. Our study was to evaluate the neutrophil gelatinase-associated lipocalin （NGAL） and cystatin C for early diagnosis of CIAKI. Methods The patients with established or suspected coronary artery disease （CAD） with the estimated glomerular filtration rate （eGFR） was more than 30 ml·min^-1·1.73 m^-2 and nor more than 90 ml·min^-1·1.73 m^-2 were continuously enrolled. The blood samples of the first 50 patients were obtained before and at 2, 4, 8, 24 and 48 hours after procedure to identify the time points at which the biomarkers reached peaks and at which the blood samples of the rest of patients were obtained. The plasma NGAL and cystatin C measure used enzyme-linked immunosorbent assay （ELISA） kit. The diagnostic characteristics of absolute and relative increasing NGAL and cystatin C for CIAKI were evaluated. Results Total 311 patients were enrolled, among whom 39 （12.5%） developed CIAKI. Plasma NGAL increased at 2 hours and reached peak at 4 hours after procedure, while plasma cystatin C increased at 2 hours and reached peak at 24 hours after procedure. Thus, we determine rational point of time at 4 hours for NGAL and at 24 hours after procedure for cystatin C, respectively. The plasma NGAL at 4 hours after CM exposure showed largest area under curve （AUC） of 0.662 （95% confidence interval （CI）： 0.565-0.758, P=0.002） with 51.5% sensitivity and 80.6% of specificity. The relative increasing 25% of NGAL showed the best sensitivity and specificity of 0.872 and 0.808, respectively, with maximum Youden index of 0.680, while cystatin C with relative increasing more than 25% had 76.9% of sensitivity and 81.2% of specificity. Combined two biomarkers might get more than 90% of specificity. Conclusions Single measurement of NGAL or cystatin C had poor sensitivity and specificity; however, the relative increasing 25% of NGAL at 4 hours after CM exposure demonstrated higher diagnostic values for CIAKI. Combining relative increasing plasma NGAL with relative increasing plasma cystatin C might perform better for early diagnosis of CIAKI.

Urinary neutrophil gelatinase-associated lipocalin(NGAL)and serum cystatin C measurements for early diagnosis of acute kidney injury in children admitted to PICU

Background Acute kidney injury(AKI)is common in critically ill children with significant mortality and morbidity.Serum creatinine is an insensitive and late biomarker compared to newly proposed AKI biomarkers.Methods Prospective study in pediatric intensive care unit(PICU)over three months to compare between serum cystatin-C(s-Cys-C)and urinary neutrophil gelatinase-associated lipocalin(uNGAL)as AKI biomarkers at multiple time points with pediatric risk,injury,failure,loss,end-stage renal disease(pRIFLE)classification in diagnosing AKI.Results Forty children were recruited.Of these 40 children,22 developed AKI according to pRIFLE criteria.There was no significant difference between AKI and non-AKI in age(P=0.29).Post cardiac surgery,renal insult was the main cause of AKI(27.3%).There was a twofold increased risk of incident AKI in those patients with high baseline uNGAL at PICU admission and almost a fourfold increased risk in patients with high baseline s-Cys-C at PICU admission.uNGAL levels were highly predictive of AKI during the follow-up period[area under the curve(AUC)=0.76,95%confidence interval(CI)0.61-0.92].The cutoff point with the highest correctly classified proportion was 223 ng/mL(≥12 centiles)which correctly predict 80.0%patients with AKI,with a corresponding sensitivity of 72.7%and a specificity of 89.9%.AUC for s-Cys-C was 0.86(95%CI 0.75-0.97),and the highest correctly classified proportion was 1009μg/L(≥13 centiles);75%of patients with AKI,with a corresponding sensitivity of 63.6%and a specificity of 88.9%.Conclusion uNGAL and s-Cys-C predicts AKI early in critically ill children.

Effect of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomi Compatibility on Uric Acid Metabolism and Urinary Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 in Rats with Hyperuricemia

Objective：To explore the effects of Rhizoma Polygoni Cuspidati and Ramulus Cinnamomicompatibility（PR） on uric acid metabolism and the expression of urinary neutrophil gelatinase-associated lipocalin（NGAL） and kidney injury molecule-1（KIM-1） in rats with hyperuricemia. Methods：Seventy male Sprague Dawley（SD） rats were randomly divided into 7 groups with 10 rats per group, including the normal group, model group, allopurinol group, benzbromarone group and PR groups at 3 doses（3.5, 7, 14 g/kg）. Except the normal group, rats of the other groups were intragastrically administered 100 mg/kg hypoxanthine and 250 mg/kg ethambutol, and subcutaneously injected with 200 mg/kg potassium oxonate. All rats were continuously modeled for 17 days, and gavaged with corresponding drugs. The rats of the normal and model groups were gavaged with saline, once a day, for 2 weeks. The levels of serum uric acid（SUA）, blood urea nitrogen（BUN） and creatinine（Cr） were determined. In addition, the contents of NGAL and KIM-1 in urine and the m RNA and protein expressions of xanthine oxidase（XOD） in liver of hyperuricemia rats were measured by reverse transcription polymerase chain reaction（RT-PCR） and Western blot, respectively. Moreover, the pathological changes of kidney were analyzed by hematoxylin and eosin（HE） stain method. Results：Compared with the normal group, the levels of SUA, BUN, NGAL and KIM-1 and the expressions of hepatic XOD m RNA and protein in the hyperuricemia rats were increased significantly（P〈0.01）. PR significantly decreased the levels of SUA, BUN, NGAL and KIM-1 and down-regulated the m RNA and protein expressions of hepatic XOD（P〈0.05 or P〈0.01）. In addition, the pathological changes of kidney were significantly suppressed by oral administration of PR. Conclusions：PR ameliorated uric acid metabolism and protected renal function, the underlying mechanism was mediated by decreasing the levels of SUA, BUN, NGAL and KIM-1, inhibiting the expression of hepatic XOD and ameliorating the pathological change of kidney.

Urine neutrophil gelatinase-associated lipocalin at SICU admission predicts for cardiac surgery-associated acute kidney injury

Background Acute Kidney Injury （AKI） is a common and serious complication of cardiovascular surgery. There is a need to find biomarkers that are involved in the etiology of cardiac surgery-associated acute kidney injury （CSA-AKI） and have an earlier response to acute kidney injury. The association between urine neutrophil gelatinase-associated lipocalin （NGAL） concentrations and AKI progression is not well established. Methods The prospective-cohort study included 1631 consecutive adult patients undergoing cardiac surgery at Fuwai Hospital between September 2012 and November 2013. AKI defined by Acute Kidney Injury Network （AKIN） criteria with a postoperative increase in plasma creatinine 〉/50% baseline or/〉0.3 mg/dL. Urine NGAL was measured us- ing latex particle-enhanced turbidimetric immunoassay. Associations between Urine NGAL levels and AKI were determined by estimating areas under receiver operating characteristic curves （AUC）. Results A total of 438 （26.9%） patients developed CSA-AKI. And the patients were divided into four groups： 1193 non-AKI patients, 368（22.6%） patients with AKIN stage I AKI, 49（3.0%） with AKIN stage 2 AKI and 21（1.3%） with AKIN stage 3 AKI. urine NGAL concentrations at surgical intensive care unit （SICU） admission were significantly related to AKI severity. The AUCs for urine NGAL were for AKIN stage 1 （0.54±0.02）, AKIN stage 2 （0.67±0.04）, and AKIN stage 3 （0.76±0.06）, respectively. Conclusions Urinary NGAL is associated with CSA-AKI and its progression, indicating their potential use as prognostic markers. Urine NGAL level measured at SICU admission predicts the development of severe AKI after cardiac surgery.

尿肾损伤分子1、血清胱抑素C和尿中性粒细胞明胶酶相关性脂质运载蛋白预测子痫前期发病和早期肾损伤的价值

目的探讨新型生物学标志物尿肾损伤分子1(KIM-1)、血清胱抑素C和尿中性粒细胞明胶酶相关性脂质运载蛋白(NGAL)与子痫前期的关系及预测子痫前期发病和早期肾损伤的价值。方法选择2014年10月至2015年7月在吉林大学第二医院住院的30例重度子痫前期孕妇、30例轻度子痫前期孕妇作为子痫前期组,并选取同期住院足月分娩的60例健康孕妇作为对照组。采用ELISA法测定尿KIM-1和尿NGAL,采用免疫浊度法测定血清胱抑素C。结果子痫前期组孕妇的尿KIM-1、尿NGAL、血清胱抑素C水平明显高于对照组(均P<0.05),随着病情进展各指标均逐渐升高。体质量指数(BMI)、肾小球滤过率(eGFR)、尿蛋白/肌酐比值、尿KIM-1、血清胱抑素C和尿NGAL是子痫前期发生的危险因素;尿KIM-1、血清胱抑素C、尿NGAL及联合预测因子作为子痫前期早期肾损伤筛查指标的灵敏度分别为83.3%、75.0%、88.9%、96.8%;特异度分别为72.7%、70.0%、75.6%、86.4%。结论尿KIM-1、血清胱抑素C和尿NGAL的水平可反映子痫前期的病情进展和子痫前期肾损伤的程度。尿KIM-1、血清胱抑素C、尿NGAL联合检测对子痫前期早期肾损伤有更高的预测价值。

尿NGAL在新生儿窒息后急性肾损伤诊治中的临床价值

目的探讨尿中性粒细胞明胶酶相关脂质运载蛋白(uNGAL)检测在新生儿窒息后急性肾损伤诊治中的临床价值。方法选择2016年9月—2017年9月我院新生儿科因围产期窒息住院的足月新生儿为研究对象进行前瞻性研究,根据生后1周内是否发生急性肾损伤(AKI),分为AKI组和非AKI组。检测患儿生后24 h内uNGAL水平和生后1周内血清肌酐(Scr)、尿素氮(BUN)水平,并进行组间比较。绘制ROC曲线分析生后24 h内uNGAL对窒息新生儿AKI的诊断价值。结果共纳入114例窒息新生儿,其中39例并发AKI,发生率34.2%,轻度窒息组AKI的发生率为27.2%(24/88),明显低于重度窒息组的57.69%(15/26),差异有统计学意义(P<0.05)。AKI组和非AKI组之间生后24 h内Scr、BUN水平差异无统计学意义,AKI组患儿生后24 h内uNGAL、uNGAL/Ucr显著高于非AKI组,差异均有统计学意义(P<0.05)。AKI组Ⅰ期(危险期)16例、Ⅱ期(损伤期)14例、Ⅲ期(衰竭期)9例,各期之间生后24 h内uNGAL差异有统计学意义,且随着AKI程度的加重,uNGAL水平逐渐增高(P<0.05)。绘制生后24 h内uNGAL诊断窒息新生儿AKI的ROC曲线,计算ROC曲线下面积(AUC)为0.842(95%CI:0.770～0.915,P<0.01),诊断临界值为118μg/L,此时敏感度为87.2%,特异度为94.7%。结论 uNGAL是早期诊断新生儿窒息后AKI的敏感、特异性指标,其水平升高可以反映肾功能损伤的严重程度。

慢性间质性肾炎中NGAL的表达及其作用的研究

目的了解慢性间质性肾炎(chron ic in terstitia l nephritis,C IN)患者肾组织中NGAL的表达及NGAL与肾小管-间质病理损害程度的关系。方法免疫组化观察正常肾组织和C IN患者肾组织NGAL的表达,以及NGAL阳性强度与小管-间质病理损害程度的关系。结果C IN患者肾组织表达NGAL较正常组增强;其小管NGAL阳性强度与小管-间质病理损害程度呈负相关。结论NGAL在C IN肾小管-间质病理损害中起重要作用。

中性粒细胞明胶酶相关载脂蛋白与慢性肾脏病

慢性肾脏病（chronic kidney disease,CKD）在普通人群的发病率约为10%-16%,死亡率及心血管疾病发生风险高,带来沉重的医疗负担。近期研究发现,中性粒细胞明胶酶相关载脂蛋白（neutrophil gelatinase-associated lipocalin,NGAL）与CKD有紧密联系,提示其在慢性肾脏病的诊断、治疗和监测等多方面具有重要价值。本文就NGAL的生物学功能、来源、结构形式及其在CKD中作用的相关研究进展作一综述。

黄芩苷对脓毒症大鼠早期肾功能损伤的保护作用

目的:通过观察黄芩苷对脓毒症大鼠血清中性粒细胞明胶酶相关载脂蛋白(NGAL)浓度的影响,探讨黄芩苷对脓毒症大鼠肾功能损伤的早期保护作用。方法:采用盲肠结扎穿孔术(CLP)制备SD大鼠脓毒症模型。实验大鼠随机分成假手术组、模型组、黄芩苷干预组(每组各24只),每组大鼠再随机分为0h、3 h、6 h、24 h4个亚组(每组各6只)。黄芩苷组在造模后立即经腹腔给予黄芩苷120 mg/kg共2 mL液体,假手术组和模型组则给予等量%0.9氯化钠液腹腔注射。每组大鼠在4个时间点(CLP术后0h、3 h、6 h、24 h)采集血标本和肾组织标本。HE染色观察肾组织病理改变;检测血清NGAL和肌酐浓度和用免疫组织化学法测定肾组织肿瘤坏死因子α(TNF-α)水平。结果:与假手术组相比,模型组大鼠血清NGAL和肌酐浓度显著升高(P<0.05),术后3 h开始升高,术后24 h继续升高;肾组织TNF-α水平也显著升高(P<0.05),术后3 h开始升高,术后24 h仍升高;术后24 h肾组织HE染色显示肾组织内大量炎症细胞浸润。与模型组相比,黄芩苷干预组术后3 h、6h和24 h血清NGAL和肌酐浓度以及肾组织TNF-α水平均显著降低(P<0.05),肾脏组织的炎症病理改变也明显减轻。结论:黄芩苷对脓毒症大鼠早期肾功能损伤有保护作用。

顺铂致大鼠急性肾损伤肾组织细胞凋亡及NGAL的相关性研究

目的:研究顺铂(Cisplatin,CDDP)致大鼠急性肾损伤(AKI)模型中肾组织细胞凋亡及肾组织中性粒细胞明胶酶相关脂质运载蛋白(NGAL)变化及相关性。方法:将36只健康雄性Wistar大鼠随机分为盐水对照组(CN组)与顺铂模型组(CP组),CP组为腹腔单次注射顺铂10 mg/kg,CN组腹腔注射同顺铂组等容量生理盐水,观察应用顺铂后12、24、48、96、144 h各组大鼠血清肌酐(Scr),肾组织细胞凋亡及NGAL变化。结果:与CN组相比,CP组48 Scr开始升高,144 h达峰值;CP组12 h肾组织凋亡细胞开始增多,48 h增加最明显;CP组12 h NGAL在肾小管上皮细胞中表达增强(P<0.05),48 h表达最明显。肾组织细胞凋亡同NGAL表达显著相关(r=0.925,P<0.01)。结论:细胞凋亡可能是CDDP致大鼠AKI早期致病机制之一,NGAL不仅是早期肾损伤的标记物,还可能参与AKI发病机制。

中性粒细胞明胶酶相关脂质运载蛋白对冠状动脉旁路移植术后急性肾损伤的早期诊断价值

目的评价血浆中性粒细胞明胶酶相关脂质运载蛋白（NGAL）对非体外循环冠状动脉旁路移植（CABG）术后急性肾损伤（AKI）的早期诊断价值。方法连续入选自2010年1月至2011年1月因确诊冠状动脉粥样硬化性心脏病入院，拟行择期非体外循环CABG治疗的患者231例。AKI定义为CABG术后48h内最高血清肌酐绝对值升高≥0．3mg／，d1（26．4μmol／L），或较基线水平升高≥50％。用酶联免疫吸附试验方法检测术前及术后2h血浆NGAL水平，采用受试者工作特征曲线来评价其对AKI的诊断价值，诊断Cut-off值采用约登指数最大值对应的点。结果231例患者中有37例（16．0％）发生AKI。发生AKI患者术前及术后2h血浆NGAL浓度分别为（69±25）和（112±29）μg/L，差异有统计学意义（P〈0．01）；未发生AKI的患者术前和术后2h血浆NGAL浓度分别为（66±24）和（71±21）μg／L，差异有统计学意义（P=0．004）；所有患者术前血浆NGAL浓度差异无统计学意义（P=0．501），而发生AKI的患者术后2h血浆NGAL浓度明显高于未发生AKI的患者，差异有统计学意义（P〈0．01）。术后2h血浆NGAL水平的药时曲线下面积最大为0．899（95％置信区间：0．843～0．954，P〈0．01）。采用约登指数最大标准选择Cut—off值为85．6μg／L，敏感性和特异性分别为0．865和0．851。结论血浆NGAL可以作为非体外循环CABG术后发生AKI的早期诊断标志物。

中性粒细胞明胶酶相关蛋白与急性有机磷农药中毒急性肾损伤的关联研究

目的:检测急性有机磷农药中毒(acute organophosphorus pesticide poisoning,AOPP)患者血清中性粒细胞明胶酶相关蛋白(serum neutrophil gelatinase-associated lipocalin,sNGAL)的水平,并分析其与中毒程度和急性肾损伤(acute kidney inju-ry,AKI)的相关性。方法:将105例AOPP患者根据其乙酰胆碱酯酶(AchE)水平分为轻度组(35例)、中度组(38例)、重度组(32例);门诊体检健康者30例为对照组。分别检测对照组、实验组入院时、入院后1d、3d、5d的sNGAL水平,分析其与中毒程度、时间变化的相关性。结果:AOPP时AKI的发生率为86.7%,通过sNGAL诊断灵敏度为87.9%,特异度100%。入院时sNGAL的阳性率达76.2%,各中毒组的sNGAL浓度均与对照组有差异(P<0.01),其浓度和阳性率均与中毒程度高度正相关(P<0.05)。血液灌流前后sNGAL浓度有明显差异(P<0.01)。结论:sNGAL是诊断AOPP早期AKI的敏感指标,其与中毒程度呈高度正相关,能反映AKI发生及恢复的过程;血液灌流治疗利于AKI恢复。

基于CdTe量子点测定中性粒细胞明胶酶相关载脂蛋白的免疫荧光层析法

建立了一种基于CdTe量子点标记技术测定中性粒细胞明胶酶相关载脂蛋白（NGAL）的免疫层析法。用水相法制备的CdTe量子点作为荧光探针标记于NGAL的一株单抗，采用双抗体夹心法，制备了检测NGAL的层析试纸条，用于测定NGAL的含量。NGAL的线性范围为41-2050μg·L^-1，检出限为27．35μg·L^-1。对NGAL不同浓度的质控品连续测定10次，测定值的相对标准偏差在3．6％-9．7％之间。方法应用于尿液样品的分析，结果与酶联免疫吸附测定法对照，两种方法所得结果间无显著偏差。

急性胰腺炎与分子水平标志物研究进展

目前临床上主要通过血尿淀粉酶、血清脂肪酶、炎症指标等实验室检测结果和腹部B超、CT等影像学检查诊断评估急性胰腺炎。与传统的诊断评估方法相比,分子生物学的快速发展为急性胰腺炎早期诊断和病情评估提供了新的思路途径。本文对国内外急性胰腺炎的新型生物分子标志物的研究进展进行综述。