转化生长因子-β1和基质金属蛋白酶-9的表达在儿童IgA肾病中的临床意义  

Expression and role of transforming growth factor-β1 and matrix metalloproteinase 9 in IgA nephropathy children

作　　者：初梅[1] 李华荣[1] 王京晶[1] 邹继珍[2] 耿海云[1] 涂娟[1] 曹力[1] 陈朝英[1] 陈大坤[1] 苏白鸽[3] 姚勇[3] 丁洁[3] 

机构地区：[1]首都儿科研究所附属儿童医院肾内科,100020 [2]首都儿科研究所附属儿童医院病理科,100020 [3]北京大学第一医院儿科

出　　处：《中华实用儿科临床杂志》2014年第13期1017-1021,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：首都儿科研究所所级课题

摘　　要：目的 探讨儿童IgA肾病血清、尿液、肾组织转化生长因子-β1（TGF-β1）、基质金属蛋白酶-9（MMP-9）的表达与临床、病理的关系,寻找以上指标与儿童IgA肾病严重程度和预后的相关性,探索儿童IgA肾病相对无创、准确、可重复性强的生物学指标.方法 选择2009年7月至2013年1月经肾组织活检明确诊断为IgA肾病患儿54例作为观察组;体检健康的55例儿童为健康对照组.对2组进行血清、尿液TGF-β1、MMP-9检测.将34例IgA肾病的肾组织和3例正常肾组织进行TGF-β1、MMP-9免疫组织化学染色.根据血尿和蛋白尿的程度将观察组分为孤立性血尿型、血尿和蛋白尿型及肾病综合征型.根据Lee氏分级标准,将光镜结果分为Ⅰ～Ⅴ级.肾小管间质病变按Katafuchi分级分为0～Ⅲ级.根据免疫球蛋白沉积种类进行免疫分型：IgA型、IgA ＋IgG型、IgA＋ IgM型或IgA＋ IgG＋ IgM型.结果 儿童IgA肾病血清、尿液TGF-β1、MMP-9水平较健康儿童明显升高,差异均有统计学意义（P均＜0.05）.儿童IgA肾病的3个临床分型（孤立性血尿型、血尿和蛋白尿型、肾病综合征型）的血清、尿液TGF-β1、MMP-9水平差异均无统计学意义（P均＞0.05）.Lee氏分级≥Ⅲ级的患儿血清TGF-β1、MMP-9水平较＜Ⅲ级者明显升高,差异均有统计学意义（P均＜0.05）,而尿液TGF-β1、MMP-9水平在以上2组病理分级中比较差异均无统计学意义（P均＞0.05）.儿童IgA肾病的各免疫分型之间的血清、尿液TGF-β1、MMP-9水平比较差异均无统计学意义（P均＞0.05）.TGF-β1和MMP-9在IgA肾病肾间质和肾小管的表达与Katafuchi病理分级的严重程度相一致.结论 血清TGF-β1和MMP-9的水平在评估儿童IgA肾病肾脏病理分级和病情严重程度中具有一定作用,也许可以作为新的无创、可重复性强的生物学指标,以弥补肾脏病理不易用于随时评估儿童IgA肾病病情进展的局限性.Objective To study the association of transforming growth factor-β1 （TGF-β1）,matrix metalloproteinase 9 （MMP-9） in serum,urinary and renal tissue of IgA nephropathy （IgAN） in children.In order to explore the noninvasive and easy repeatable biomarker,for assessing the severity and disease progression in IgAN children.Methods Fifty-four children with biopsy-proven IgAN and 55 healthy normal children （healthy control group） were enrolled between Jul.2009 and Jan.2013.The IgAN group was divided into 3 clinical groups according to their clinical features：isolated hematuria （IH） group （IH group,20 cases）,hematuria and proteinuria （HP） group （HP group,16 cases）,and nephritic syndrome group （NS group,18 cases）.Patients were divided into 2 groups according to their Lee＇s pathologic classification：grade Ⅰ ＋ Ⅱ group（Lee＇s Ⅰ ＋ Ⅱ,39 cases）,and grade Ⅲ ＋ Ⅳ group（Lee＇s Ⅲ ＋ Ⅳ,15 cases）.There were no grade Ⅴ in the study.The injury of renal tubules and interstitium was divided into 0-Ⅲ grades according to Katafuchi pathologic classification.IgAN group was also divided into 4 groups according to their immunophenotype：IgA（7 cases）,IgA ＋ IgG group（9 cases）,IgA ＋ IgM group（10 cases）,IgA ＋ IgG ＋ IgM group（28 cases）.The expressions of TGF-β1 and MMP-9 of each group were measured by enzyme-linked immunosorbent assay（ELISA）.Immunohistochemistry was used to measure the expressions of TGF-β1 and MMP-9 in the paraffin sections of 34 IgAN and 3 normal renal tissue,and ELISA was used to measure the levels of TGF-β1 and MMP-9 in serum and urine.SPSS 16.0 statistical software was used.Results The levels of TGF-β1 and MMP-9 in serum and urinary of the IgAN group were significantly higher than those in the healthy control group（all P ＜ 0.05）.Both the levels of TGF-β1 and MMP-9 in serum and urinary of the 3 clinical groups in the IgAN children were no statistically significant（all P ＞ 0.05）.The serum TGF-β1 and MMP-9

关 键 词：IGA肾病 转化生长因子-Β1 基质金属蛋白酶-9 肾组织 儿童 

分 类 号：R726.9[医药卫生—儿科]