CAJ | 학술논문

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(laminin α1)和α5(laminin α5)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laminin αl、laminin α5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≥175%.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laminin α1主要在肾小球系膜区,GBM无显色;laminin α5则沿着GBM均匀显色.Alport患者的laminin α1在肾小球系膜区的分布低于对照组,主要在GBM上显色;laminin α5在GBM上的分布低于对照组;GBM上laminin α1与laminin α5半定最评分呈高度负相关(r=-0.83,P＜0.001).GBM增厚及撕裂范围与laminin α1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laminin α5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laminin α1和laminin α5与GBM增厚和撕裂的超微病理改变有关.
목적:관측Alport종합정환자신소구기저막(GBM)초미결구개변여GBM상층점련단백α1(laminin α1)화α5(laminin α5)분포적관계.방법:1998년1월지2008년7월재북경대학제일의원경신활검병리학진위Alport종합정적환자20례,령외선택6례신종류절제술후환자적정상신조직작위대조.재투사전경하측량GBM후도이급증후화시렬적범위.대신조직석사절편진행laminin αl、laminin α5면역조직화학염색,대기재GBM적분포진행반정량평분:0분위0%,1분위≤25%,2분위25%～50%,3분위50%～75%,4분위≥175%.결과:투사전경하관찰Alport종합정환자적GBM균출현불동정도적증후화시렬분층.면역조직화학현시,정상대조조적laminin α1주요재신소구계막구,GBM무현색;laminin α5칙연착GBM균균현색.Alport환자적laminin α1재신소구계막구적분포저우대조조,주요재GBM상현색;laminin α5재GBM상적분포저우대조조;GBM상laminin α1여laminin α5반정최평분정고도부상관(r=-0.83,P＜0.001).GBM증후급시렬범위여laminin α1적반정량평분균정정상관(분별위r=0.76,P＜0.001;r=0.56,P=0.015),여laminin α5적반정량평분균정부상관(분별위r=-0.59,P=0.010;r=-0.53,P=0.025).결론:Alport종합정환자GBM중이상분포적laminin α1화laminin α5여GBM증후화시렬적초미병리개변유관.
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 al 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 al and laminin α5 (r =-0. 83, P＜0. 001). The extension of thickening or splitting GBM was positively correlated with scores of laminin al in GBM ( r = 0. 76, P＜0.001; 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 al and laminin α5 in GBM is correlated with GBM thickening and splitting in human Alport' s syndrome.