微小RNA在糖尿病肾病患者血清中的表达及临床意义

目的 探讨糖尿病肾病发生、进展过程中血清微小RNA (microRNA,miRNA)表达谱及其临床意义.方法 应用miRNA基因芯片检测10例糖尿病肾病患者、10例糖尿病尿蛋白正常患者及10例健康对照者血清miRNA表达谱.实时荧光定量PCR法对66例糖尿病肾病(微量蛋白尿者36例,大量蛋白尿者30例)、40例糖尿病尿蛋白正常者及40例健康对照者进行血清miRNA表达谱验证,分析血清差异表达的miRNA与糖尿病肾病临床参数的关系.结果 实时荧光定量PCR法验证得到miR-150-5p、miR-155-5p、miR-30e-5p及miR-3196在糖尿病微量蛋白尿患者组(n=36)、糖尿病尿蛋白正常者组(n=40)及健康对照组(n=40)血清样本中表达差异有统计学意义(P＜0.05).miR-150-5p (P=0.005)和miR-155-5p (P=0.006)在糖尿病微量蛋白尿组(n=36)及糖尿病大量蛋白尿组(n=30)血清中表达差异有统计学意义.大量蛋白尿组血清miR-150-5p和miR-155-5p表达水平分别是微量蛋白尿组的2.3倍、1.5倍.同时发现,miR-150-5p和miR-155-5p与糖尿病肾病患者的估算肾小球滤过率和尿蛋白排泄率具有明显相关性.结论 miR-150-5p和miR-155-5p可能参与糖尿病肾病发生及发展的病理过程;血清miR-150-5p和miR-155-5p有望成为DN早期诊断及判断预后的潜在分子标志物.

Expression and clinical significance of microRNA in the serum of patients with diabetic nephropathy

Objective To investigate the expression and clinical significance of serum microRNA (miRNA) expression profiling in the occurrence and progression of diabetic nephropathy. Methods The miRNA expression profiling was detected by miRNA TaqMan Low Density Array chip from 10 patient with diabetic nephropathy, 10 diabetes patients with normoalbuminuria and 10 health control. Real-time quantitative PCR was applied to verify the result of miRNA array in serum samples of 66 patients with diabetic nephropathy (36 patients with microalbuminuria, 30 patients with macroalbuminuria), 40 diabetes patients with normoalbuminuria and 40 health control. And the relationship of differetial expression with clinical features was analyzed. Results miR-150-5p, miR-155-5p, miR-30e-5p and miR-3196 being validated by real-time quantitative PCR differentially expressed in 3 groups of serum samples from the diabetes patients with microalbuminuria (n=36), with normoalbuminuria (n=40) and health control (n=40) (P＜0.05). Serum miR-150-5p (P=0.005) and miR-155-5p (P=0.006) changed significantly between diabetes patients with microalbuminuria (n=36) and with macroalbuminuria (n=30). Compared with the diabetes patients with microalbuminuria, serum miR-150-5p and miR-155-5p increased by 2.3 and 1.5 times in macroalbuminuria group, respectively. Estimated glomerular filtration rate and urinary albumin excretion rate significantly correlated with serum miR-150-5p and miR-155-5p level. Conclusions miR-150-5p and miR-155-5p may be involved in the process of pathological mechanisms of diabetic nephropathy. Serum miR-150-5p and miR-155-5p may be regarded as potential biomarkers to diagnosis the occurrence and development of diabetic nephropathy.