尿胞外体亮氨酸氨基肽酶及二肽基肽酶在糖尿病肾病中的变化  

Changes of urinary exosomal leucine aminopeptidase and dipeptidyl peptidase 4 in diabetic nephropathy

作　　者：孙爱丽[1] 胡晓燕[2] 关广聚[1] 邓浩萍[3] 刘元涛[1] 陈诗鸿[1] 刘军莉[1] 邓景惕[2] 

机构地区：[1]山东大学第二医院,山东济南250033 [2]山东大学医学院生物化学教研室,山东济南250012 [3]莱州市人民医院,山东莱州261419

出　　处：《中国病理生理杂志》2011年第4期775-778,共4页Chinese Journal of Pathophysiology

基　　金：山东省自然科学基金资助项目(No.ZR2009CM061)

摘　　要：目的:探讨2型糖尿病患者尿液胞外体的亮氨酸氨基肽酶(exosome-LAP)及二肽基肽酶4(exosome-DPP4)的水平变化在糖尿病肾病发展过程中的意义。方法:选取127例2型糖尿病患者,根据24h尿白蛋白肌酐比(UACR)分为糖尿病正常白蛋白尿组(DM,43例)、微量白蛋白尿组(DN1,50例)和大量白蛋白尿组(DN2,34例)。另选健康对照组34例。采用特异性的单克隆抗体提纯胞外体,酶联免疫吸附法(ELISA)检测尿液胞外体的exosome-LAP和exosome-DPP4。同时检测糖化血江蛋白(HbA1c)、血胆固醇(CH)、肌酐(CR)、尿素氮(BUN)。应用多元逐步回归方法分析DPP4及LAP与HbA1c、CH、UACR、CR、BUN相关性。结果:DM、DN1、DN2组exosome-LAP和exosome-DPP4水平均显著高于正常组(均P<0.01);与DM组比较,DN2组exosome-LAP水平显著升高(P<0.01)。尿exosome-LAP、exosome-DPP4与HbA1c、CH、UACR、CR、BUN显著相关。逐步多元回归分析显示,CH、UACR是exosome-LAP的独立危险因素(均P<0.01);UACR、HbA1c是exosome-DPP4的独立危险因素(均P<0.01)。结论:Exosome-LAP和exosome-DPP4水平与糖尿病肾病严重程度密切相关,以上指标对于糖尿病肾病的诊断及预后估计具有一定临床价值。AIM：To investigate the changes of urinary exosomal enzymes and the correlation with diabetic nephropathy. METHODS：Thirty-four healthy volunteers and 127 patients of type 2 diabetes mellitus（T2DM）were included in the study.The healthy volunteers served as control.The patients with T2DM were divided into 3 groups based on their 24 h urinary albumin/creatinine ratio（UACR）：50 patients with microalbuminuria in early DN group（DN1）,34 patients with macroalbuminuria in overt DN group（DN2）and 43 patients without albuminuria in DM group.The levels of urine exosomal leucine aminopeptidase（exosome-LAP）and exosomal dipeptidyl peptidase 4（exosome-DPP4）were determined by enzyme-linked immunosorbent assay（ELISA）.The following methods were used to determine the biochemical parameters;liquid chromatography for glycated hemoglobin（HbA1c）,chemical modification method for cholesterol （CH）,Jaffe-kinetic assay for creatinine（CR）and urease-GLDH method for blood urea nitrogen（BUN）.Multiple stepwise linear regressions were used to analyze the relationship of exosome-LAP or exosome-DPP4 with HbA1c,CH, UACR,CR and BUN.RESULTS：The levels of exosome-LAP and exosome-DPP4 in DM,DN1 and DN2 groups were significantly higher than those in control group（P〈0.01）.The exosome-LAP in DN2 group was significantly higher than that in DM group.Correlation analysis showed that the levels of urinary exosome-LAP and exosome-DPP4 were positively correlated with HbA1c,CH,UACR,CR and BUN.Multiple stepwise linear regression analysis showed that CH and UACR were independent determinants for exosome-LAP（P〈0.01）,and UACR and HbA1c were independent determinants for exosome-DPP4（P〈0.01）.CONCLUSION：Urine exosome-LAP and exosome-DPP4 are correlated with the severity of diabetic nephropathy.These parameters may serve as clinical markers for the diagnosis and prognosis evaluation of diabetic nephropathy.

关 键 词：糖尿病肾病 白蛋白尿 尿胞外体 亮氨酸氨肽酶 二肽基肽酶4 

分 类 号：R58[医药卫生—内分泌]