Relationship between serum neutrophil gelatinase-associated lipocalin levels and cognitive impairment, anxiety, and depressive symptoms in acute ischemic stroke

BACKGROUND Acute ischemic stroke(AIS)is a significant global health issue with increasing incidence owing to aging populations and rising cardiovascular risk factors.In addition to physical impairments,AIS frequently leads to neuropsychiatric co-mplications,such as cognitive impairment,anxiety,and depressive symptoms,which adversely affect patients’quality of life and rehabilitation.Neutrophil ge-latinase-associated lipocalin(NGAL)has emerged as a potential biomarker for various conditions,including AIS.This study investigated the association bet-ween serum NGAL levels at admission and neuropsychiatric complications in patients with AIS.neuropsychiatric complications in patients with AIS.METHODS Between January 2022 and December 2023,150 patients with AIS were enrolled.Serum NGAL levels were measured at admission using an enzyme-linked immu-nosorbent assay.Cognitive function was assessed using the Mini-Mental State Examination,while anxiety and depressive symptoms were evaluated using the Hospital Anxiety and Depression Scale at discharge.The relationship between serum NGAL levels and cognitive impairment,anxiety,and depressive symptoms was analyzed using multivariate logistic regression,adjusted for potential con-founders of age,sex,body mass index,smoking status,hypertension,diabetes mellitus,dyslipidemia,previous stroke,and stroke severity.RESULTS The mean age of the participants was 65.4±10.2 years,and 58%were males.Prevalence rates of cognitive impairment,anxiety,and depressive symptoms at discharge were 34.7%,28.0%,and 32.0%,respectively.Serum NGAL levels were significantly higher in patients with cognitive impairment(median:5.6 ng/mL vs 3.2 ng/mL,P<0.001),anxiety(median:5.1 ng/mL vs 3.5 ng/mL,P=0.002),and depressive symptoms(median:5.4 ng/mL vs 3.3 ng/mL,P<0.001),compared to those without these conditions.Multivariate logistic regression analysis showed that higher serum NGAL levels at admission were independently associated with cognitive impairment[odds ratio(OR)=1.42,95%confidence interval(CI):1.18-1.71,P<0.001],anxiety(OR=1.28,95%CI:1.09-1.51,P=0.003),and depressive symptoms(OR=1.39,95%CI:1.16-1.67,P<0.001)after adjusting for potential confounders.CONCLUSION Elevated serum NGAL levels were independently associated with cognitive impairment,anxiety,and depressive symptoms in patients with AIS;and may function as potential biomarkers for patients at risk.

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.

PTEN、CA125、sVEGFR1、NGAL在子宫内膜癌患者血清中的表达及与病理特征的关系

目的 探讨第10号染色体缺失的磷酸酶及张力蛋白同源基因(PTEN)、糖类抗原125(CA125)、可溶性血管内皮生长因子受体-1(sVEGFR1)、中性粒细胞明胶酶相关脂质载运蛋白(NGAL)在子宫内膜癌(EC)患者血清中的表达及与病理特征的关系。方法 选取2019年1月至2021年6月于在邯郸市第一医院行全子宫切除术并经病理诊断的120例EC患者为研究组,选择同期80例良性病变子宫内膜患者为对照组,用酶联免疫吸附法检测并比较2组患者血清PTEN、CA125、sVEGFR1、NGAL水平,收集2组临床病理资料,分析血清PTEN、CA125、sVEGFR1、NGAL与研究组患者病理特征的关系。结果 研究组血清CA125、NGAL水平高于对照组,血清PTEN、sVEGFR1水平低于对照组(P<0.05)。分化程度越低血清CA125、NGAL水平越高,血清PTEN、sVEGFR1水平越低(P<0.05);临床分期Ⅲ~Ⅳ期患者血清PTEN高于Ⅰ~Ⅱ期(P<0.05);临床分期Ⅲ~Ⅳ期、有淋巴结转移、浸润深度≥50%患者血清CA125、NGAL水平升高,血清sVEGFR1水平降低(P<0.05)。血清PTEN与临床分期呈负相关,与分化程度呈正相关(P<0.05);血清CA125、NGAL与临床分期、淋巴结转移、浸润深度呈正相关,与分化程度呈负相关(P<0.05);血清sVEGFR1与临床分期、淋巴结转移、浸润深度呈负相关,与分化程度呈正相关(P<0.05)。结论 CA125、NGAL在EC患者血清中呈高表达,PTEN、sVEGFR1呈低表达,均与EC患者病理特征有一定相关性,可作为EC早期诊断与疾病进展的潜在生物学标志物。

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.

NGALR干扰抑制NF-κB通路阻断肾小管细胞上皮间充质转分化

目的:分析中性粒细胞明胶酶相关脂钙蛋白受体(NGALR)干扰对高糖诱导HK-2细胞的活性和上皮间质细胞转分化(EMT)的影响及其机制。方法:将HK-2细胞分成对照组(正常培养的HK-2细胞)、模型组(用30mM高浓度的葡萄糖诱导HK-2细胞24h)、si-NGALR NC组(先用30mM高浓度的葡萄糖诱导HK-2细胞24h,然后再转染si-NGALR NC质粒4h)、si-NGALR组(先用30mM高浓度的葡萄糖诱导HK-2细胞24h,然后再转染NGALR干扰质粒4h)、PDTC组(先用30mM高浓度的葡萄糖诱导HK-2细胞24h,然后加入100μM NF-κB抑制剂PDTC)、PDTC+si-NGALR组(先用30mM高浓度的葡萄糖诱导HK-2细胞24h,然后加入100μM NF-κB抑制剂PDTC作用1h,再转染NGALR干扰质粒4h)。各组细胞均在37℃、5%CO2的环境中培养。CCK8法检测细胞增殖,qRT-PCR检测NGALR mRNA,流式细胞术检测细胞凋亡,Western Blot检测NGALR、NGAL蛋白和NF-κB通路蛋白(NF-κB p65和p-NF-κB p65)及EMT相关蛋白(Snail和Vimentin)表达。结果:与对照组相比,模型组细胞增殖能力显著下降(P<0.01),凋亡率上升(P<0.01),NGALR、NGAL、Snail、Vimentin及NF-κB p65磷酸化的蛋白表达均上升(P<0.01)。与模型组相比,si-NGALR组和PDTC组细胞增殖能力显著上升(P<0.01),凋亡率下降(P<0.01),NGALR、NGAL、Snail、Vimentin及NF-κB p65磷酸化的蛋白表达均下降(P<0.01)。与PDTC组相比,PDTC+si-NGALR组变化趋势更加显著。结论:NGALR干扰通过调控NF-κB通路阻断高糖诱导肾小管EMT,抑制细胞的异常增殖和凋亡,减轻肾小管损伤。

NGAL、OPG、RANKL及DAS28对RA骨质疏松的预测作用

目的:通过检测血中中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)、骨护素(osteoprotegerin,OPG)、病情活动度评分DAS28与NF-κB配体的受体(receptor activator of NF-κB ligand,RANKL)预测类风湿关节炎(rheumatoid arthritis,RA)骨质疏松意义。方法:选择119例RA患者(RA组,其中并发骨质疏松症的51例)及68例健康者(对照组),用ELISA法检测RA组与健康对照组的NGAL、骨形成指标OPG及骨吸收指标RANKL,详细记录骨矿物质含量(bone mineral density,BMD)、病情活动性评分(disease activity score 28,DAS28)与临床、实验室资料。结果 :①RA病人血清NGAL、RANKL水平较健康对照组明显增高(均P=0.000),血清OPG、OPG/RANKL、BMD水平较对照组明显降低(均P=0.000),差异有统计学意义。②RA合并有骨质疏松症的病人血清NGAL[(152.12±28.34)ng/mL]、RANKL水平[(112.23±18.45) pmol/L]及DAS28(4.21±0.56)评分较无骨质疏松症组明显增高[NGAL(124.50±18.52) ng/mL,P=0.000;RANKL (103.89±14.14) pmol/L,P=0.008;DAS28 3.52±0.70,P=0.000];血清OPG[(114.35±17.00) ng/L]、OPG/RANKL(1.06±0.24)、BMD(-3.73±0.69)水平较无骨质疏松症组明显降低[OGP(120.56±15.35) ng/L,P=0.039;OPG/RANKL 1.18±0.24,P=0.006;BMD-0.57±0.76,P=0.000],差异有统计学意义。③Spearman相关分析显示,NGAL、DAS28与BMD严重程度呈正相关,rs分别为0.532、0.437,P值分别为0.000、0.000,其相关性对RA合并有骨质疏松症有早期诊断的实际意义。④采用ROC曲下线面积分析,当DAS28的最佳诊断参考值为4.11时(诊断敏感性和特异性分别为68.6%、77.9%)、NGAL最佳诊断参考值为148.80 ng/mL时(诊断敏感性和特异性分别为60.8%、89.7%)、RANKL为100.77 pmol/L时(诊断敏感性和特异性分别为64.7%、54.4%),可考虑RA患者合并有骨质疏松症的可能。结论:血清NGAL、RANKL作为炎症指标,其水平及DAS28活动性评分大于等于相应的最佳诊断值可以考虑RA病人合并有了骨质疏松症的可能,对调整治疗方案、极早干预骨质疏松症的发生与发展有一定的临床价值。

血清NGAL和sLox-1水平在妊娠期高血压疾病中的变化及临床意义

目的分析妊娠期高血压孕妇血清中性粒细胞明胶酶脂质运载蛋白(Neutrophil gelatinase lipocalin,NGAL)及凝集素样氧化型低密度脂蛋白受体-1(lectin-like oxidized low-density lipoprotein receptor-1,sLOX-1)的变化,探讨NGAL、sLox-1在妊娠期高血压疾病孕妇中的临床意义。方法收集本院确诊为妊娠期高血压疾病孕妇56例为实验组,正常孕妇60例为对照组,采用酶联免疫吸附法测定两组血清中NGAL和sLox-1的水平并进行比较。结果实验组NGAL、sLox-1血清水平明显高于对照组(P<0.05)。实验组血清NGAL和sLox-1分娩后较前下降(P<0.05)。血清NGAL和sLox-1的表达随病情加重逐渐增强,子痫前期重度组表达最强。结论血清NGAL和sLox-1水平随妊娠期高血压疾病病情改变,可能参与了妊娠期高血压疾病的发病机制。

妊娠高血压疾病胎盘组织中NGAL和sLox-1的表达及临床意义

目的 分析妊娠高血压疾病孕妇胎盘组织中中性粒细胞明胶酶脂质运载蛋白（NGAL）,凝集素样氧化型低密度脂蛋白受体-1（sLox-1）的变化,探讨NGAL、sLox-1在妊娠高血压疾病中的临床意义.方法 收集2011年3月～2014年1月在笔者医院确诊为妊娠高血压疾病孕妇68例为实验组,正常孕妇70例为对照组,采用免疫组化及Western blot法测定两组胎盘组织中NGAL和sLox-1的表达并进行比较.结果 两组孕妇胎盘组织中均可见NGAL及sLox-1的表达,但实验组中表达水平明显高于对照组,两组比较差异有统计学意义（F=43.310,P＜0.05）;实验组中NGAL及sLox-1的表达随患者病情加重表达愈强,在子痫前期重度组最明显（F =213.167,P＜0.05）.结论 NGAL和sLox-1参与了妊娠高血压疾病病理生理改变,其发病机制与炎性因子活动有关.

糖化白蛋白调控肾损伤相关分子与Toll样受体信号通路及齐墩果酸对其干预作用的研究

目的探讨人近端肾小管上皮细胞(HK-2细胞系)在糖化白蛋白(glycated albumin,GA)与齐墩果酸(oleanolic acid,OA)作用下,肾损伤分子-1 (kidney injury molecule-1,KIM-1)、中性粒细胞明胶酶相关载脂蛋白(neutrophil gelatinase-associated lipocalin,NGAL)及Toll样受体信号通路相关分子的表达情况。方法采用GA及OA处理HK-2细胞24 h,real-time PCR检测KIM-1、NGAL以及p38丝裂原活化蛋白激酶(mitogen activated protein kinase,MAPK)、白细胞介素-1受体相关激酶4(interleukin-1receptor-associated kinase 4,IRAK4)、Toll样受体(Toll-like receptor,TLR) 1、TLR2、TLR7和TLR9的mRNA表达,ELISA法检测细胞上清液KIM-1与NGAL水平,Western blotting法检测细胞内p38 MAPK、IRAK4、TLR1、TLR2、TLR7和TLR9蛋白表达。结果与对照组比较,GA能显著上调KIM-1、NGAL mRNA与蛋白的含量(P<0.05),并促进p38 MAPK、IRAK4、TLR1、TLR2 mRNA及蛋白的表达(P<0.05);加入OA能显著抑制上述作用(P<0.05)。结论 GA能够上调KIM-1和NGAL的表达与释放,激活Toll样受体信号通路,对人近端肾小管上皮细胞造成损伤;而加入OA能够有效干预GA调控的损伤。

硫酸镁联合胰激肽释放酶治疗重度子痫前期疗效及对孕妇血清NGAL、sFlt-1和sEng影响

目的:探讨硫酸镁联合胰激肽释放酶治疗重度子痫前期(SPE)疗效及对孕妇血清中性粒细胞明胶酶相关脂运蛋白酶(NGAL)、可溶性血管内皮生长因子受体1(sFlt-1)和可溶性内皮因子(sEng)水平的影响。方法:选取2016年12月—2019年12月本院收治的SPE患者85例,随机数字法分为对照组(n=42)和观察组(n=43),对照组给予硫酸镁治疗,观察组给予硫酸镁联合胰激肽释放酶治疗,比较两组临床疗效、血压水平、子宫动脉和脐动脉血流状态、血清NGAL、sFlt-1、sEng水平、炎症因子[白细胞介素-10(IL-10)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]及分娩结局。结果:观察组治疗有效率(88.4%)高于对照组(64.3%)(P<0.05);治疗后观察组SBP、DBP、MAP,以及脐动脉和子宫动脉的PI、S/D均低于对照组,血清NGAL、sFlt-1、sEng水平低于对照组,血清IL-6、TNF-α水平低于对照组,IL-10高于对照组,分娩结局优于对照组(均P<0.05)。结论:硫酸镁联合胰激肽释放酶治疗SPE疗效显著,可稳定血压水平,降低血管阻力和血清NGAL、sFlt-1、sEng、IL-4、IL-6水平,并改善分娩结局。

针刺联合麻杏石甘汤加减对重症急性胰腺炎相关性肺损伤及外周血NGAL、TLR4的影响

目的观察针刺联合麻杏石甘汤加减对重症急性胰腺炎(SAP)相关性肺损伤(ALI)及外周血中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、Toll样受体4(TLR4)的影响。方法选取SAP并发ALI患者80例,按随机数字表法分为对照组与观察组各40例,对照组给予常规治疗,观察组加用针刺联合麻杏石甘汤加减治疗。对比两组临床症状及预后性指标,治疗前后评价急性生理与慢性健康评分(APACHEⅡ)、序贯器官衰竭评估量表(SOFA)和中医证候量表评分,检测血浆NGAL水平及外周血单核细胞中TLR4蛋白表达,检测下游炎症因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平。结果治疗后,两组的APACHEⅡ评分、SOFA评分及中医证候积分均显著下降,且观察组均显著低于对照组(P<0.05);两组外周血NGAL、TLR4蛋白、IL-1β、IL-6和TNF-α水平均显著降低,且观察组均显著低于对照组(P<0.05)。观察组的腹痛腹胀缓解、恶心呕吐缓解、血清淀粉酶(AMS)恢复时间、机械通气时间均较对照组缩短(P<0.05),但两组住ICU时间、28 d病死率差异无统计学意义(P>0.05)。结论针刺联合麻杏石甘汤加减治疗SAP合并ALI能够促进病情缓解,减轻肺损伤指标,其机制可能与抑制外周血BGAL、TLR4及相关炎症因子表达有关。

孟鲁司特对大鼠小肠缺血再灌注伤肾脏CysLTsR1表达及肾功能的影响

目的研究孟鲁司特对大鼠小肠缺血再灌注伤(IIR)肾脏CysLTsR1表达及肾功能的影响。方法30只成年雄性wistar大鼠随机分为对照组、缺血再灌注组(模型组)和孟鲁司特组,每组各10只。采用钳闭大鼠肠系膜上动脉建立IIR模型。建模3 h后观察各肾组织病理学形态并评分;免疫组化、Western blot和RT-PCR法检测肾组织CysLTR1和中性粒细胞明胶酶相关脂质运载蛋白表达水平;生化分析仪检测血清尿素氮(BUN)、肌酐(Cr)。结果模型组与对照组比较肾组织损伤严重,病理损伤Paller评分明显增高[(408.9±17.3)分vs(110.3±10.0)分],CysLTR1 mRNA水平显著升高[(3.60±0.84)vs(1.93±0.11)],CysLTR1蛋白表达显著升高,血清BUN和Cr值均显著升高[(21.82±2.39)vs(6.25±0.56);(57.85±8.18)vs(25.55±2.92)],NAGL表达显著升高[(677.67±6.03)vs(576.67±12.66)],差异有统计学意义(P<0.01)。与模型组相比较,孟鲁司特组病理损伤Paller评分显著低于模型组[(323.4±14.9)分vs(408.9±17.3)分];CysLTR1 mRNA水平显著降低[(2.80±0.36)vs(3.60±0.84)];CysLTR1蛋白表达显著降低(P<0.01);血清BUN和Cr均显著降低[(13.50±1.31)vs(21.82±2.39);(30.85±3.94)vs(57.85±8.18)],差异有统计学意义(P<0.01),NAGL表达降低[(645.00±38.20)vs(677.67±6.03)],差异有统计学意义(P<0.05)。结论孟鲁司特可减轻小肠缺血再灌注肾损伤,其机制与其抑制肾组织CysLTR1的活化有关。