尿蛋白3项联合尿N-乙酰-β-D-氨基葡萄苷酶检测在妊娠期糖尿病患者肾损伤中的临床应用价值

目的探讨尿α_1-微球蛋白(α_1-mG)、尿β_2-微球蛋白(β_2-mG)、尿视黄醇结合蛋白(RBP)联合尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)检测在妊娠期糖尿病(GDM)肾损伤中的临床应用价值。方法选取滕州市中心人民医院临床明确诊断的妊娠期糖尿病患者174例和孕期正常体检者(对照组)56例作为研究对象。GDM患者按照血生化肾功能诊断结果分为肾功能异常组70例和肾功能正常组104例;按照肾小球滤过率(GFR)大小分为GDMⅠ组106例和GDMⅡ组68例。分别检测晨尿α_1-mG、β_2-mG、RBP及NAG水平,使用SPSS 19.0进行统计学分析。结果 GDM肾功能异常组和GDM肾功能正常组尿α_1-mG、β_2-mG、RBP、NAG水平明显高于对照组(P<0.05);GDM肾功能异常组尿α_1-mG、β_2-mG、RBP水平明显高于GDM肾功能正常组(P<0.05)。GDMⅠ组和GDMⅡ组尿α_1-mG、β_2-mG、RBP、NAG水平明显高于对照组(P<0.05);GDMⅡ组尿α_1-mG、β_2-mG、RBP水平明显高于GDMⅠ组(P<0.05)。GDM肾功能异常组和GDM肾功能正常组尿蛋白3项联合NAG检测阳性率均明显高于单一检测(P<0.05)。结论尿α_1-mG、β_2-mG、RBP及NAG可用于GDM肾早期损伤的诊断,尿α_1-mG、β_2-mG、RBP浓度变化与GDM肾损伤程度呈正相关;4项联合检测更有利于GDM肾早期损伤的筛查、诊断以及疾病进展的判断,有一定的临床应用价值。     

矽肺患者血清N-乙酰-β-D氨基葡萄糖苷酶的活性及其临床价值研究

本文利用分光光度法测定了50例矽肺患者、18例0~ +期接尘工人、29例0期接尘工人及51例正常对照受检者血清N-乙酰-β-D氨基葡萄糖苷酶(NAG)活性。结果表明,正常对照受检者血清NAG活性(X±SD)为10.27±1.64u/L,矽肺患者为16.94±4.52u/L,0~+期接尘工人为14.63u/L。矽肺患者与0~+期接尘工人血清NAG的活性经统计学检验无显著性差异,但二者均显著高于0期接尘组(9.56±2.6u/L)和正常对照组。本实验测得皿清铜蓝蛋白的结果表明,矽肺患者血清铜蓝蛋白高于正常对照组和0期接尘工人,但0~+期接尘工人与0期接尘工人无显著性差异。矽肺患者血清NAG与铜蓝蛋白之间存在正相关性。     

混苯损害肾功能的初步观察

近年来研究表明,汽油等有机溶剂对肾功能有损害作用~([1~3]),但混苯与肾功能的关系国内未见报道。本文试图通过对尿β_2-微球蛋白(β_2-mG尿白蛋白(Alb)、尿IgG等测定以观察混苯作业与肾功能的关系。     

二氧化硅粉尘对接触工人的肾毒性研究

通过测定二氧化硅粉尘接触工人和矽肺病人尿白蛋白（ａｌｂ）、β＿２－微球蛋白（β＿２－ＭＧ）和Ｎ－乙酰－β－Ｄ－氨基葡萄糖苷酶（ＮＡＧ）排出量，来确定肾毒性与二氧化硅粉尘接触的关系。结果表明：接尘工人和矽肺病人尿ａｌｂ、β＿２－ＭＧ和ＮＡＧ排出量显著高于对照组，其排出量增加与接尘工人接尘时间有关，而与矽肺病人脱离接尘的时间无关。证实二氧化硅粉尘可导致接触者出现慢性、非可逆性肾毒性反应。     

煤矿接矽尘工人血清TAC、TGF-β1表达水平与矽肺的相关性

目的探讨煤矿接矽尘工人血清中总抗氧化能力(total antioxidant capacity，TAC)、转化生长因子-β1(transfonning growth factor-β1，TGF-β1)表达水平与矽肺的相关性。方法采用限制性三次样条(restricted cubic spline，RCS)结合Logistics回归，分析随机选取的137例煤矿工人(接尘组)和94例壹期矽肺患者(病例组)血清中TAC与TGF-β1的剂量-效应关系及其对矽肺发病的影响。结果TAC、TGF-β1、年龄及吸烟在接尘组和病例组之间差异有统计学意义(P<0.05)；接尘组血清TAC水平工龄11?20年组高于1?10年组，差异有统计学意义(P<0.05)；病例组血清TGF-β1水平工龄11?20年组低于1?10年、21?38年组，差异均有统计学意义(P<0.05)。RCS模型分析结果显示，接尘组和病例组TAC、TGF-β1水平间均存在相关性，且在接尘组中两者呈非线性关系(总体关联性检验χ2=8.010，P=0.046和χ2=7.870，P=0.049；非线性检验χ2=6.580，P=0.037和χ2=3.340，P=0.188)。多因素分析显示，调整潜在混杂因素后(年龄、文化程度、接尘工龄、开始接尘年龄和吸烟)，TGF-β1与矽肺发病风险升高有关(OR=1.022，95%CI 1.006?1.039)，TAC与矽肺发病风险降低有关(OR=0.897，95%CI 0.847?0.951)。结论煤矿接尘工人及矽肺患者血清TAC、TGF-β1含量与矽肺相关。     

尿中微量蛋白和尿N-乙酰-β-D-氨基葡萄糖苷酶的检测对儿童过敏性紫癜肾炎的意义

目的探讨尿中微量蛋白和N-乙酰-β-D-氨基葡萄糖苷酶(NAG)的检测对儿童过敏性紫癜肾炎的意义。方法根据尿常规结果将过敏性紫癜患儿分为过敏性紫癜(HSP)组和过敏性紫癜肾炎(HSPN)组,同时选取健康儿童为对照组。比较各组尿中m Alb、α_1-MG、β_2-MG、TRf、Ig G和NAG的水平。结果 HSPN组中尿m Alb、α_1-MG、β_2-MG、TRf、NAG和Ig G的含量均明显高于HSP组和对照组,差异有统计学意义(P0.05);HSP组中尿m Alb、α_1-MG、β_2-MG、TRf和NAG的含量均高于对照组,差异有统计学意义(P0.05);Ig G含量与对照组比较,差异无统计意义(P0.05)。HSP组中尿中微量蛋白和NAG联合检测阳性率为77.8%,明显高于各单项检测的阳性率,差异均有统计学意义(P0.05)。结论联合检测尿中微量蛋白和NAG的水平可较好的反映过敏性紫癜患儿的早期肾损伤。     

系统性红斑狼疮患者尿α1-微球蛋白与尿微量蛋白测定及意义

目的　了解α1-微球蛋白 (α1-mG)与尿微量白蛋白 (u -Alb)对系统性红斑狼疮 (SLE)患者早期肾损害的诊断价值。方法　通过放射免疫方法对 31例SLE患者 (尿常规正常组 10例 ,尿常规异常组 2 1例 )及 19例健康对照组的α1-mG、β2 -微球蛋白 (β2 -mG)、u -Alb进行检测。结果　SLE病人尿α1-mG、β2 -mG、u -Alb明显高于正常对照组 (P <0 .0 1)。无论尿常规正常与否 ,其尿α1-mG、β2 -mG、u -Alb均明显高于健康对照组 (P <0 .0 1)。结论　尿α1-mG及u -Alb是系统性红斑狼疮患者早期肾损害的敏感指标     

尿视黄醇结合蛋白、尿微量白蛋白、尿β_2微球蛋白、尿NAG酶联合检测在糖尿病早期肾损伤诊断中的意义

目的探讨尿视黄醇结合蛋白(RBP)、尿微量白蛋白(mALB)、尿β_2微球蛋白(β_2-MG)、尿NAG酶联合检测在糖尿病早期肾损伤诊断中的意义。方法收集89例糖尿病伴早期肾损伤患者及同期102例健康体检者尿液标本,胶乳增强免疫比浊法检测尿RBP、尿mALB、尿β_2-MG及尿NAG酶浓度,分析其与糖尿病早期肾损伤相关性。结果糖尿病伴早期肾损伤组患者尿RBP、尿mALB、尿β_2-MG及尿NAG酶浓度均显著高于健康对照组(P0.05)。得出诊断模型Y(健康对照)=(-0.013×RBP测定值)+(-0.003×MALB测定值)+(-0.064×β_2MG测定值)+(0.526×NAG测定值)+(-4.632)和Y(患者)=(-0.018×RBP测定值)+(0.000×MALB测定值)+(0.263×β_2MG测定值)+(0.741×NAG测定值)+(-9.473)。结论尿RBP、尿mALB、尿β_2-MG及尿NAG酶均为糖尿病早期肾损伤危险因素,且据此建立诊断模型。     

汽油、甲苯、二甲苯接触者尿β_2-微球蛋白测定与探讨

对147名汽油接触者、77名甲苯和二甲苯接触者、70名正常对照者进行了尿β_2-mG测定研究。汽油组和混苯组尿β_2-mG的几何均值分别为135.34μg/g·Cr和230.09μg/g·Cr;对照组为84.98μg/g·Cr。接触组各工龄段尿β_2-mG均显著高于对照组(P<0.01),且随工龄增长而增高,较蛋白定量更敏感和特异。提示尿β_2-mG可作为汽油、甲苯、二甲苯对早期肾小管损害的敏感检测指标。     

模拟高原人体试验中健康人尿液酶及β_2-微球蛋白和白蛋白的变化

本文在低压实验舱内研究了11名男性健康受试者在300m平原和3500m、4500m两高度人体尿液酶(NAG、GGT、AAP、ALP)和β_2-MG,Alb在锻练前后的变化。结果表明,尿液NAG在高原条件下较平原增高1～2倍(P<0.05)较其余三种酶灵敏;β_2-MG和Alb在高原缺氧后也显著增高;提示高原缺氧可导致肾小球滤过和肾小管重吸收的轻度损害。锻练对NAG和β_2-MG有较好的改善作用,而对Alb改变不明显。     

A study of silica nephrotoxicity in exposed silicotic and non-silicotic workers.

The possible human nephrotoxicity of silica has often been suggested by previous anecdotal reports and uncontrolled clinical studies of silicotic patients. Urinary excretions of albumin, alpha-1-microglobulin (AMG), and beta-N-acetyl-glucosaminidase (NAG) were measured in 33 male workers exposed to silica (mean duration of employment 16 years) and 19 male age matched non-exposed subjects with no history of primary or secondary renal diseases. Significantly higher urinary excretions of albumin and AMG were found in the workers exposed to silica. Silicotic subjects (n = 7) also had significantly high excretions of albumin, AMG, and NAG. All but one of the silicotic patients had ceased exposure from three to 17 years before the study. Our findings suggest that prolonged exposure to silica is associated with chronic irreversible nephrotoxicity in exposed workers.     

A study of silica nephrotoxicity in exposed silicotic and non-silicotic workers.

The possible human nephrotoxicity of silica has often been suggested by previous anecdotal reports and uncontrolled clinical studies of silicotic patients. Urinary excretions of albumin, alpha-1-microglobulin (AMG), and beta-N-acetyl-glucosaminidase (NAG) were measured in 33 male workers exposed to silica (mean duration of employment 16 years) and 19 male age matched non-exposed subjects with no history of primary or secondary renal diseases. Significantly higher urinary excretions of albumin and AMG were found in the workers exposed to silica. Silicotic subjects (n = 7) also had significantly high excretions of albumin, AMG, and NAG. All but one of the silicotic patients had ceased exposure from three to 17 years before the study. Our findings suggest that prolonged exposure to silica is associated with chronic irreversible nephrotoxicity in exposed workers.     

尿生化指标检测在肾功能早期改变中的诊断价值

目的探讨尿生化指标检测在肾功能早期改变中的诊断价值。方法将青龙县人民医院2010年8月-2011年3月收治的100例肾病患者为研究对象,按照肾小球滤过率（GFR）的大小,将其分为肾功能正常组38例（A组）,肾功能损害组62例（B组）,另选取健康体检者40例作为对照组,测定肾病组患者治疗前后及对照组的尿胱抑素C（Cy-sC）、尿N-乙酰-D-D氨基葡萄糖苷酶（NAG）、尿β2-微球蛋白（β2-MG）、尿比重（SG）。结果肾病组的尿CysC、NAG、β2-MG显著高于对照组（P〈0.05）,尿SG显著低于对照组（P〈0.05）;B组的尿CysC、NAG、2β-MG显著高于A组（P〈0.05）,尿SG显著低于A组（P〈0.05）;肾病组经治疗后尿CysC、NAG、β2-MG较治疗前显著降低,尿SG较治疗前显著升高（P〈0.05）。结论尿生化指标可作为肾功能损害较好的检测诊断指标,在一定程度上可反映病情的严重程度,且操作简便,值得临床推广。     

镉接触工人尿镉血镉与尿β_2MG RPB含量的跟踪研究

目的:跟踪调查镉接触工人停止接触镉后尿镉、血镉的变化及肾功能损害情况,寻找镉接触指标与肾功能损害指标的关系,初步探讨职业性镉引起的肾功能特点及规律。方法:选择深圳某镍镉电池厂29名镉中毒观察对象(尿镉连续2次超过5μmol/mol肌酐)为研究对象,分析尿镉、血镉含量与尿β2-微球蛋白(β2MG)、尿视黄醇结合蛋白(RPB)排出量的关系;并通过跟踪研究他们在停止接触镉1年后,接触指标(尿镉、血镉)及肾功能损害指标的变化的规律。结果:镉中毒观察对象在停止接触1年后,尿镉由(7.16±2.81)μmol/mol肌酐下降至(7.03±2.84)μmol/mol肌酐,尿镉含量下降没有显著性差异(P>0.05);血镉明显下降,由(5.8±1.81)μg/L下降至(3.5±1.24)μg/L,有显著性差异(P<0.01);尿β2-微球蛋白含量(中位数)由1.19μmol/mol肌酐上升至1.21μmol/mol肌酐,尿视黄醇结合蛋白含量(中位数)由0.39μmol/mol肌酐上升至0.42μmol/mol肌酐,统计学秩和检验结果显示均没有显著性差异(P>0.05)。尿镉与血镉存在明显的线性正相关,相关系数(r)为0.721,(P<0.01),回归分析得出的方程为:y=1.132x+3.656,(y代表尿镉,x代表血镉)。尿镉、血镉与尿β2-微球蛋白含量的相关系数分别为0.321,0.346,统计学上均没有显著性相关(P>0.05)。结论:职业性镉中毒观察对象停止接触镉1年后,血镉明显下降,尿镉含量下降不明显,尿镉与血镉存在线性正相关,尿β2-微球蛋白、尿视黄醇结合蛋白含量总体水平变化不显著,但有个别仍可以出现肾功能异常,镉对肾功能损害存在明显个体差异性。     

Further evidence of human silica nephrotoxicity in occupationally exposed workers.

It has previously been shown that granite workers with heavy exposure to silica had glomerular and proximal tubular dysfunction evidenced by increased urinary excretions of albumin, alpha-1-microglobulin (AMG), and beta-N-acetyl-glucosaminidase (NAG). The investigation was replicated in another group of granite workers to further elucidate the exposure effect relation. The urinary excretion of albumin, alpha-1-microglobulin (AMG), beta-2-microglobulin (BMG), and beta-N-acetyl-glucosaminidase (NAG) was determined in two groups of granite workers with low and high exposure to silica. Low molecular weight proteinuria and enzymuria were significantly correlated with duration of exposure in the high but not the low exposure group. These increases were most pronounced in those with 10 or more years of heavy exposure, and in those with radiological evidence of pulmonary fibrosis, particularly those with rounded small opacities denoting classical silicosis. These results provide further evidence that prolonged and heavy exposure to silica is associated with nephrotoxic effects in granite workers.     

接触氯丙烯工人肾功能的初步观察

本文报告了某丙烯磺酸钠生产车间接触氯丙烯工人肾功能检查结果。25名工人尿蛋白几何均数与正常对照组无显著差异;尿β_2-微球蛋白几何均数明显增高,尤以工龄大于5年者为著,其中尿β_2-微球蛋白超过正常上限的2名工人可能存在轻度肾小管重吸收功能障碍。但肾功能检查结果在慢性氯丙烯中毒诊断上的意义,尚不能与周围神经检查相比拟。今后有必要选用灵敏的肾功能检查指标作深入探讨。     

Rat model of perchloroethylene-induced renal dysfunctions.

To investigate whether perchloroethylene (PCE) can induce renal disturbances and to compare morphological alterations with functional data, two groups of 12 male and female Fischer-344 mature rats were treated daily with PCE (500 mg/kg body wt in corn oil, p.o.) for 4 weeks. Sex- and age-matched control groups received corn oil only. Weekly, the urinary excretion of albumin (Alb), alpha 2 mu-globulin (alpha 2 mu) and retinol-binding protein (RBP) was measured in 24-hr urine samples using immunoassays specific for rat proteins. N-acetylglucosaminidase (NAG) activity was measured by a colorimetric assay. Electrophoretic analysis of proteinuria included SDS-PAGE and isoelectric-focusing of Alb purified from serum and urine. Weekly histopathology comprised light and electron microscopy. In the male rat, a trend toward progressive albuminuria (up to 15 times the pair-fed controls) was observed, together with transient increases in alpha 2 mu and NAG; RBP showed a twofold increase at the end of treatment. Histopathology failed to demonstrate glomerular changes, whereas it displayed alpha 2 mu accumulation and mild lesions in the S2 segment of proximal tubules. Thus, in the male rat, the selective damage to S2 was associated with "glomerular" proteinuria, the alpha 2 mu cortical content being closely correlated with albuminuria (n = 9, r = 0.92, P < 0.001). In the female rat, only minor, although statistically significant (P < 0.05), increases were recorded for Alb, whereas urinary alpha 2 mu reached up to four times the control values. As a whole, these findings suggest that PCE, like other hydrocarbons, selectively affects the tubular segment S2 in the rat. A competition with alpha 2 mu for tubular uptake could explain enhanced albuminuria. Owing to the species specificity of alpha 2 mu, caution should be exercised in extrapolating these findings to man.     

δ-氨基-γ-酮戊酸脱水酶和维生素D受体基因多态性与铅肾毒性易感性的相关研究

目的探讨δ-氨基-γ-酮戊酸脱水酶(ALAD)和维生素D受体(VDR)基因多态性以及基因-基因、基因-环境之间的联合作用对铅肾毒性的作用。方法选择233名铅作业工人,根据工人接触铅水平是否超过职业接触限值将其分为两组,分别测定血铅、尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、尿β2-微球蛋白(β2-MG)和尿肌酐,全血提取DAN基因组,多聚酶链反应-限制性片段长度多态性(PCR-RFLP)法分析ALAD和VDR基因多态性。结果超职业限值组,ALAD1-2/2-2基因型和ALAD1-1基因型工人尿NAG的浓度分别为(2.12±0.07)U/mmol Cr和(1.73±0.03)U/mmol Cr,差异具有显著性P<0.05;VDR-Bb基因型的工人尿β2-MG浓度[(20.94±0.12)μg/mmol Cr]高于携带VDR-bb基因型工人的尿β2-MG浓度[(15.28±0.09)μg/mmol Cr](P=0.01)。多因素Logistic回归分析发现,铅接触、高血铅等环境因素以及环境-基因的联合作用都是铅作业工人肾损害的危险因素,接铅水平、血铅水平、ALAD基因型和接铅水平的联合作用引起尿NAG异常的OR值分别为6.85(2.51～10.87)、2.41(1.70～3.41)、3.01(1.10～8.19)。结论在高铅浓度接触下ALAD和VDR基因型与铅肾毒性有关,ALAD-2等位基因和高铅接触是加重铅肾毒性的危险因素。     

难治性肾病肾小管功能损害及缬沙坦干预研究

目的探讨肾小管功能损害在难治性肾病（RNS）中的意义及缬沙坦干预治疗对其影响。方法RNS患者阳例及正常对照68例，79例RNS患者随机分为缬沙坦组和潘生丁组，在常规治疗的基础上，缬沙坦组加缬沙坦（80mg／d），潘生丁组加潘生丁（150mg／d）治疗12周。治疗前后采用ELISA法、生化方法及肾间质病理计量分析法分别检测全部患者肾小管功能（尿RBP、α1-MG、β2-MG、mAlb、NAG）和肾间质病理改变。结果所有RNS患者尿RBP、α1-MG、β2-MG、mAlb、NAG明显高于正常对照组（P〈0．01）。且与肾小管间质损害均呈正相关（r=0．436、0．626、0．499、0．668、0．657，P〈0．01）。干预结果显示缬沙坦组口服缬沙坦后尿系列蛋白均明显降低，而潘生丁组则无明显变化。结论RNS患者均有不同程度的肾间质损害及肾小管功能的损害，而肾小管功能损害与肾间质损害及肾小球损害程度呈正相关。及早对RNS进行ARB干预治疗可改善肾小管功能及延缓RNS的发展。     

Occupational exposure to toluene and its possible causative role in renal damage development in shoe workers

Objectives: An important, although, unprecise number of shoe workers in Leon, Mexico, are in continuous contact with toluene-based glues. The induction of renal glomerular and/or tubular lesions as a result of toluene exposure is still being discussed controversially. Our objective was to evaluate the extent of occupational exposure, assessing urinary o-Cresol excretion as a measure for toluene exposure in a population at risk as compared to a control population. Urinary albumin excretion (UAE) and N-acetyl-β-D-glucosaminidase (NAG) enzymatic activity were tested to assess renal dysfunction. Methods: A cross-sectional study was performed comparing 50 toluene-exposed shoe workers and 25 control subjects. Urinary o-cresol was assessed on first and last day of labor week from exposed subjects. A single urine sample was obtained from control subjects. Urinary Albumin excretion (UAE) and (NAG) activity were examined in 12 h urine samples in all subjects. Urine and serum creatinine were measured to asses renal function. Results: At the end of the labor week, urinary o-cresol levels were higher in samples obtained from exposed subjects. Albumin excretion was similar in the exposed and control groups. NAG activity was greater in the exposed group compared to control group (median 3.5 U/g creatinine vs 1.9 U/g creatinine, z=2.6, P=0.009). An inverse relationship was found between schooling years and the NAG enzymatic activity for the two studied groups (r= −0.27, P=0.02), Conclusions: Our findings support the hypothesis that toluene may be a factor associated with the presence of renal damage in exposed shoe workers. As NAG activity is increased, we believe the lesion initiates in the renal tubular cells.