Alport综合征患者肾小球基底膜超微结构改变与层粘连蛋白的异常分布

Correlation between ultrastructural changes of glomerular basement membrane and abnormal distribution of laminins in patients with Alport's syndrome

目的:观测Alport综合征患者肾小球基底膜(GBM)超微结构改变与GBM上层粘连蛋白α1(lamininα1)和α5(lamininα5)分布的关系。方法:1998年1月至2008年7月在北京大学第一医院经肾活检病理确诊为Alport综合征的患者20例,另外选择6例肾肿瘤切除术后患者的正常肾组织作为对照。在透射电镜下测量GBM厚度以及增厚和撕裂的范围。对肾组织石蜡切片进行lamininα1、lamininα5免疫组织化学染色,对其在GBM的分布进行半定量评分:0分为0%,1分为≤25%,2分为25%～50%,3分为50%～75%,4分为≥75%。结果:透射电镜下观察Alport综合征患者的GBM均出现不同程度的增厚和撕裂分层。免疫组织化学显示,正常对照组的lamininα1主要在肾小球系膜区,GBM无显色;lamininα5则沿着GBM均匀显色。Alport患者的lamininα1在肾小球系膜区的分布低于对照组,主要在GBM上显色;lamininα5在GBM上的分布低于对照组;GBM上lamininα1与lamininα5半定量评分呈高度负相关(r=-0.83,P<0.001)。GBM增厚及撕裂范围与lamininα1的半定量评分均呈正相关(分别为r=0.76,P<0.001;r=0.56,P=0.015),与lamininα5的半定量评分均呈负相关(分别为r=-0.59,P=0.010;r=-0.53,P=0.025)。结论:Alport综合征患者GBM中异常分布的lamininα1和lamininα5与GBM增厚和撕裂的超微病理改变有关。

Objective：To analyse the relationship of ultrastructural changes of glomerular basement membrane（GBM） and glomerular distributions of laminin α1 and laminin α5 in patients with Alport＇s syndrome.Methods： Twenty patients with Alport＇s syndrome were recruited.The thickness of GBM and the extension of thickening and splitting GBM were measured under transmission electron microscope.Normal renal tissues from 6 nephrectomies of renal carcinoma were taken as controls.Paraffin embedded sections of formalin-fixed renal tissue were processed for immunohistochemistry with monoclonal antibodies to laminin α1 and laminin α5.Their distributions in GBM were evaluated by a semiquantitative scale of positive extension： absent,0;≤25%,1;25%-50%,2;50%-75%,3;≥75%,4.Results： There were a variety of degrees of thickening or splitting GBM in patients with Alport＇s syndrome.Laminin α1 was positive in glomerular mesangial area and absolutely negative in GBM and laminin α5 was evenly positive in GBM in normal tissue.In Alport＇s syndrome,laminin α1 was much weaker in glomerular mesangial area,but strongly positive in GBM;laminin α5 in GBM was prominently reduced.There was a high negative correlation of semiquantitative scores between laminin α1 and laminin α5（r=-0.83,P0.001）.The extension of thickening or splitting GBM was positively correlated with scores of laminin α1 in GBM（r=0.76,P0.001;r=0.56,P=0.015）,and was negatively correlated with scores of laminin α5 in GBM（r=-0.59,P=0.010;r=-0.53,P=0.025）.Conclusion： Abnormal distribution of laminin α1 and laminin α5 in GBM is correlated with GBM thickening and splitting in human Alport＇s syndrome.