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富含半胱氨酸的酸性分泌糖蛋白在IgA肾病患者血、尿中的含量及肾组织中的表达
邬碧波1,2,张黎明2,梅长林1*,付莉莉1,王文靖1
0
(1.第二军医大学长征医院肾内科,解放军肾脏病研究所,上海 200003; 2.第二军医大学长征医院闸北分院肾内科,上海 200070)
摘要:
目的:测定富含半胱氨酸的酸性分泌糖蛋白(SPARC)在IgA肾病患者血液、尿液中的浓度,并观察其在肾组织中的分布和表达。方法:采用夹心ELISA法对IgA肾病患者和正常人血清和尿液中SPARC、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)进行定量检测;应用夹心ELISA法检测IL-6处理后的人肾小球系膜细胞(HMC)和人肾小管上皮细胞(HKC)SPARC蛋白的分泌水平;运用免疫组织化学SP法检测SPARC在IgA肾病患者及正常人肾组织中的表达及分布。结果:IgA肾病患者血液及尿液SPARC、TNF-α、IL-1β、IL-6的含量均显著高于正常对照组(P<0.01或P<0.05);IgA肾病患者尿液SPARC浓度显著高于血液浓度(P<0.01)。IL-6(50 pg/ml)分别作用HMC、HKC 96 h后,SPARC蛋白的表达量明显高于对照组(P<0.01),而且HKC组SPARC蛋白的表达量明显高于HMC组(P<0.01)。在正常肾组织中,SPARC在远端小管细胞仅有极微弱表达,在IgA肾病肾组织小管上皮细胞中SPARC蛋白表达较正常肾组织肾小管细胞明显增强。结论:IgA肾病时,增多的炎症因子可刺激肾小管细胞产生和分泌SPARC蛋白增加,引起血清SPARC浓度升高,可能起到一种保护性反馈抑制系膜细胞增殖的作用。
关键词:  富含半胱氨酸的酸性分泌糖蛋白  IgA肾病  血液  尿液  
DOI:10.3724/SP.J.1008.2008.00408
投稿时间:2007-07-25修订日期:2008-03-05
基金项目:上海市闸北区医学科研课题基金(2004重点学科02).
Concentrations of secreted protein acidic and rich in cysteine in serum and urine and its expression in kidney tissues of patients with IgA nephropathy
WU Bi-bo1,2,ZHANG Li-ming2,MEI Chang-lin1*,FU Li-li1,WANG Wen-jing1
(1.Department of Nephrology,Changzheng Hospital,Nephrology Institute of PLA,Second Military Medical University,Shanghai 200003,China; 2.Department of Nephrology,Zhabei Branch of Changzheng Hospital,Second Military Medical University,Shanghai 200070)
Abstract:
Objective:To investigate the concentrations of secreted protein acidic and rich in cysteine(SPARC) in the serum and urine of patients with IgA nephropathy and its expression in the kidney tissues.Methods: The concentrations of SPARC,tumor necrosis factor-α (TNF-α),interleukin 1β (IL-1β),and interleukin 6 (IL-6) in the serum and urine were measured with enzyme-linked immunosorbent assay(ELISA).The contents of SPARC protein in the culture medium of human mesangial cell (HMC) and human renal tubular epithelial cell (HKC),which had been treated with IL-6,were determined by ELISA.The expression and distribution of SPARC in IgA nephropathy and normal kidney tissues were observed by immunohistochemistry assay.Results: The concentrations of SPARC in serum and urine of IgA nephropathy patients were higher than those of the normal control subjects ( \[2.43±1.22\] μg/ml vs \[0.69±0.21\] μg/ml,\[7.73±2.81\] μg/ml vs \[1.17±1.03\] μg/ml,P<0.01).The serum levels of TNF-α,IL-1β and IL-6 in IgA nephropathy group were significantly higher than those in the control group (P<0.05); the urinary levels of TNF-α and IL-6 in IgA nephropathy group were also higher than those in the controls (P<0.01).SPARC protein secreted by HKC was higher than that by HMC (P<0.01).SPARC was weakly positive in normal distal cortical tubules.SPARC protein expression in tubular epithelial cells of IgA nephropathy patients was obviously higher than that of the normal controls. Conclusion: The secretion of SPARC by renal tubular epithelial cells is increased in patients with IgA nephropathy,which results in elevation of serum SPARC and may have a protective feedback inhibitory effect on HMC proliferation.
Key words:  secreted protein acidic and rich in cysteine  IgA nephropathy  blood  urine  kidney