膜型狼疮肾炎中NEPH1与Nephrin的研究

Study of podocyte slit diaphragm protein NEPH1 and Nephrin in membranous lupus nephritis

目的 研究肾小球足细胞相关蛋白NEPH1和Nephrin在膜型狼疮肾炎（V-LN）蛋白尿产生中的作用.方法 选择V-LN 25例,18例同期住院的特发性膜性肾病（IMN）作对照,另取5例因肾脏肿瘤行一侧肾切除的远端相对正常肾脏组织作为健康对照 检测尿常规、尿蛋白定量（24 h）、肝功能、肾功能、血脂、血清补体、尿补体（C3）及尿N-乙酰-β-D氨基葡萄糖苷酶（NAG）,2组病例肾组织作常规病理检查和NEPH1、Nephrin免疫荧光染色,激光共聚焦显微镜观察NEPH1、Nephrin表达和分布的变化,组间两两比较采用t检验.结果 2组病例尿蛋白定量（24 h）[（3.5±0.6）和（3.7±0.7）g]、血清白蛋白[（26±3）和（24±3）g/L]、血清肌酐[（108±9）和（102±8）μmol/L]、尿C3[（3.4±0.8）和（3.8±1.1）mg/L]差异无统计学意义（P〉0.05）,V-LN组血清总胆固醇[（6.3±0.9）mmol/L]、甘油三酯[（2.0±0.3）mmol/L]、血清补体C3[（0.40±0.16）g/L]、C4[（0.05±0.02）g/L]均低于IMN组[分别为（9.2±1.3）、（3.7±0.5）mmol/L,（0.72±0.06）、（0.12±0.01）g/L]（P〈0.05）,而V-LN组尿红细胞和尿NAG（P〈0.05,P〈0.01）均高于IMN组 间接免疫荧光显示V-LN及IMN患者肾组织中NEPH1、Nephrin的表达均减弱,但V-LN组的表达减弱不如IMN组明显.结论 足细胞相关蛋白NEPH1、Nephrin表达下降可能参与了LN蛋白尿的发生,其他机制如肾小管上皮细胞的损害可能在V-LN蛋白尿的发生中也起了一定作用.

Objective To investigate the expression of slit diaphragm proteins of glomerular podocyte,such as NEPH1 and Nephrin in type Ⅴ lupus nephritis （V-LN）. Methods Twenty-five patients with V-LN and 18 patients with idiopathic membranous nephritis （IMN） were enrolled into the study, and 5 normal renal samples were the normal control group. Twenty-four hours urine protein excretion, serum albumin, creatinine, triglyceride, total cholesterol, serum C3, C4, urine C3 and NAG were tested respectively.Glomerular lesions were measured by light microscopy. The expressions of NEPH1 and Nephrin were determined by indirect immunofluorescent staining. The statistical treatment was used t-test. Results Compared to the IMN group, the 24 hours urine protein excretion and the concentrations of serum albumin, creatinine, urine C3 were not significantly different while the triglyceride, total cholestorel, serum C3, C4 were significantly decrease in the V-LN group （P〈0.05）. Urine NAG was increased in the V-LN group （P〈0.01）. By indirect immuno-fluorescent histochemitry examination, the glomerular expressions of NEPH1 and Nephrin were significantly decreased in both V-LN and IMN. Compared with the IMN group, the decrease of NEPH1 and Nephrin expression was more remarkable in the V-LN group. Conclusion The expression changes of NEPH1 and Nephrin may play an important pathogenic role in proteinuria of Ⅴ lupus nephritis. Renal tubular epithelial cell damage may play a role in proteinuria of V-LN.