【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。更多还原

【Abstract】 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.更多还原