采用SELDI技术检测肾移植患者尿液蛋白质指纹图谱诊断慢性移植肾肾病

Establishment of early warning diagnostic systems of the chronic allograft nephropathy with polypeptide or protein fingerprints in urine

目的 探讨应用表面增强激光解吸离子化飞行时间质谱（SELDI）技术检测慢性移植肾肾病（CAN）患者尿液蛋白质指纹图谱峰值的意义。方法 实验分为4组。对照组：身体健康者6例；肾功能衰竭组：慢性肾功能衰竭者5例，未进行肾移植；肾功能恢复组：肾移植术后移植肾功能恢复正常的长期存活者22例；CAN组：肾移植术后发生CAN者16例。取各组受试者早晨中段尿液，应用SELDI技术检测蛋白质指纹图谱峰值。结果 经检测，肾功能恢复组和CAN组之间有3个蛋白质的表达存在差异（P〈0．05）；在肾功能衰竭组和肾功能恢复组之间有7个蛋白质表达存在差异（P〈0．05），其中3个可能为潜在性的标记物（P〈0．01）；在对照组和肾功能衰竭组之间有19个蛋白质表达存在差异（P〈0．05），其中12个可能为潜在性的标记物（P〈0．01）。结论 SELDI技术可通过比较不同患者尿液蛋白质谱间的差异，分析出能区分CAN和其他肾病的特异性蛋白质峰值，初步筛选出有意义的差异蛋白，可为CAN的早期临床诊断提供一个可行的检测途径和方法。

Objective To develop the early warning system of chronic allograft nephropathy （CAN） using surface enhanced laser desorption/ionization-time of flight-mass spectrometry （SELDI- TOF-MS）. Methods All the subjects were divided into 4 groups： control group, 6 healthy volunteers; renal failure group, 5 cases of chronic renal function failure without any transplantation; longsurvival group, 22 long-survived patients with well-functioning renal allograft; CAN group, 16 cases of CAN. Urinary peptide or protein peaks were detected by SELDI-TOF-MS systems and immobile metal anion chip （IMAC）. Results Interesting 120 protein or polypeptides peaks were profiled and 3 were differentially expressed between CAN group and long-survival group （P〈0. 05）. Thirty-one interesting peaks were detected and there were 7 differentially expressed proteins between long-survival group and renal failure group （P〈0. 05）, and 3 of them were significantly expressed （P〈0. 01）. Thirty-eight interesting peaks were profiled and 19 were differentially expressed between control group and renal failure group （P〈0. 05） and 12 of them were significantly expressed （P〈0. 01 ）. Conclusion There may be differentially expressed protein and polypeptides between the CAN group and other nephropathy groups, and those detected proteins and polypeptides are potentially biomarker candidates for early clinical diagnosis of CAN.