CD2相关蛋白在肾病综合征中的表达及意义

目的观察不同病理类型的原发性肾病综合征(nephrotic syndrome,NS)患者肾小球足细胞中CD2相关蛋白(CD2AP)的表达,探讨其与足细胞损伤的关系。方法选取原发性NS患者54例,10例同期肾肿瘤切除患者正常肾组织作为对照。肾活检后常规染色观察肾脏组织病理改变,肾组织行免疫荧光法CD2AP和肾小球上皮细胞蛋白-1(GLEPP1)双重标记,对肾小球CD2AP的表达进行定位;分别用real time PCR和免疫组化SP法检测组织中CD2AP的表达,采用real time PCR检测nephrin的表达,透射电镜观察足细胞的结构变化,并定量测量足突密度。结果 (1)NS患者肾小球中CD2AP的表达及nephrin的表达下调,足细胞足突不同程度融合,足突密度降低。(2)病理表现为微小病变性肾病(minimal change disease,MCD)、局灶性节段性肾小球硬化(focal segmental glomerulosclerosis,FSGS)和膜性肾病(membranous nephropathy,MN)的NS患者CD2AP表达及nephrin表达较对照组明显降低,且CD2AP与nephrin表达呈正相关,病理表现为MCD和FSGS的NS患者CD2AP表达与足突密度呈正相关。结论本研究首次发现原发性NS患者肾小球足细胞中CD2AP的表达降低,且在MCD和FSGS中与足细胞病变程度相关,提示CD2AP低表达在足细胞病变为主的肾小球疾病中发挥重要作用。CD2AP有利于诊断足细胞病变的早期检测,对CD2AP表达减低进行早期干预可能有助于延缓疾病进展。

Expression of CD2AP on podocytes with different pathological types of nephrotic syndrome

Purpose To investigate the CD2AP expression of the renal podocytes in patients with nephrotic syndrome,and to study the association between expression of CD2AP and podocyte injury.Methods 54 patients with nephrotic syndrome(NS) were studied,and 10 patients with renal tumor undergone nephrectomy were enrolled as control.Renal pathological change after renal biopsy was bserved.CD2AP and GLEPP1 by immunofluorescence double staining were performed.The renal CD2AP was detected by immunohistochemistry and quantitive real time PCR.The renal nephrin was detected by quantitive real time PCR.Structure of podocyte foot process were observed and measured by electron microscopy.Results(1)Compared to the control,the expression of CD2AP and nephrin were decreased significantly in the patients with NS.And because foot processes came to fusion or disappeared,its density decreased.(2) Among the NS patients,the patients with minimal change disease(MCD) and focal segmental glomerulosclerosis(FSGS) have the CD2AP expression significant which lower than the control patients.And in the groups of MCD and FSGS,the expression of CD2AP is positively correlated with the density of foot process.Conclusions The expression of CD2AP in podocyte of the patients with primary nephrotic syndrome was decreased significantly.And this change is correlated with the degree of podocyte injury in patients with MCD and FSGS.The downregulation of CD2AP expression may play an important role in glomerular disease,especially in the disease with podocyte injury as the main change.Intervention aimed at CD2AP in the early stage can delay or arrest the progression of glomerular disease.