微小病变性肾病早期差异尿蛋白质组分析

Analysis of differential urinary proteome in experimental minimal change nephropathy

目的筛选微小病变性肾病早期尿蛋白标志物。方法以阿霉素肾病大鼠作为该病动物模型,采用LC-MS/MS蛋白质组学技术,非标记法蛋白质相对定量方法,分别分析尿全蛋白质组及ConA偶联琼脂糖珠富集的尿糖蛋白组的变化。结果尿全蛋白质组分析得到25个差异蛋白,分别来源于血浆蛋白、免疫炎性细胞分泌蛋白及泌尿道特异分泌蛋白等,参与不同的致病过程,如血流动力学改变、足细胞损伤及免疫功能紊乱等;尿糖蛋白质组分析得到21个差异蛋白,其中12个蛋白(57%)与未进行富集实验得到的差异蛋白不同,说明两种方法具有互补性,可以从不同角度对肾脏病变进行刻画。结论这些差异蛋白可作为微小病变性肾病早期诊断的候选标志物,对其功能的进一步验证将有助于其发病机制的解析。

Objective To screen early urine protein markers for minimal change nephropathy.Methods Adriamycin nephropathy was employed as minimal change nephropathy model.Urinary protein and ConA captured glycoproteins were respectively profiled.Results By profiling urine proteome,25 differential proteins were identified.These differential proteins were from leaked plasma proteins,secreted proteins from immuno-and inflammatory cells,specifically asecreted proteins from urinary tract,and so on.They took part in different pathogenic process,eg.hemodynamic changes,podocytes injury,immunological disorder and so on.By profiling ConA-enriched urinary glycoproteome,21 differential proteins were identified,among which 12（57%）were different from the above 25 differential proteins.This indicates that the knowledge of urine glycoproteome is complementary to urine proteome in understanding kidney condition.Conclusion These differential proteins can be potential indicators of minimal change nephropathy,and can help better understand the pathogenesis by further studying their functions.