2型糖尿病患者血清miR-130b水平与尿白蛋白排泄率的相关性研究

The correlation between urinary albumin excretion rate and the level of serum miR-130b in patients with type2 diabetes mellitus

探讨2型糖尿病患者血清miR-130b的表达，分析其与尿白蛋白排泄率的相关性，从而推断miR-130b与糖尿病肾脏损伤的关系。收集243例2型糖尿病患者，根据尿白蛋白／肌酐比率（UACR），将2型糖尿病患者分为3组：正常白蛋白尿组（UACR〈30mg／g，n=103）；微量白蛋白尿组（UACR30～300mg／g，n=86）、大量白蛋白尿组（UACR〉300mg／g，n=54）。采用实时定量PCR检测血清miR-130b的表达，ELISA法测定血清转化生长因子p1（TGF-β1）和肿瘤坏死因子OL（TNF—d）。选取同期年龄、性别匹配的健康体检者59名作为对照组。结果显示2型糖尿病患者血清miR-130b含量较对照组显著下降（P〈0．01），并与UACR呈负相关（r=-0．463，P〈0．01），2型糖尿病患者各组miR-130b水平随UACR的升高而递减。血清miR-130b与血尿素氮、血肌酐、UACR呈负相关（r=-0．295、-0．316、-0．463，均P〈0．05）；而与估算的肾小球滤过率呈正相关（r=0．367，P〈O．01）；血清miR-130b与稳态模型评估的胰岛素抵抗指数、三酰甘油、低密度脂蛋白胆固醇、TNF—a、TGF—β1呈负相关（r=-0．257、-0．345、-0．242、-0．562、-0．622，均P〈0．01）。血清miR-130b可能成为糖尿病肾病早期肾脏损伤与肾损伤程度的新型生物标志物。血循环中miR-130b可能参与调节糖尿病肾病发生及发展。

The aim of this study was to detect the levels of serum miR-130b expression in patients with type 2 diabetes mellitus and to analyze their correlation with diabetic renal damage. 243 patients with type 2 diabetes mellitus were divided into three groups according to urinary albumin/creatinine ratio （UACR） ： norlnoalbuminuria group （ UACR 〈30 rag/g, n = 103 ） , microalbuminuria group （ UACR 30-300 mg/g, n = 86 ） , and macroalbuminuria group （ UACR〉 300 mg/g, n = 54 ）. The levels of serum miR-130b were validated by realtime polymerase chain reaction. Serum transforming growth factor-β1 （ TGF-β1 ） and tumor necrosis factor-a （TNF-a） were determined by enzyme-linked immunosorbent assay （ELISA） in all patients and59 healthy volunteers. Compared with control group, the level of serum miR-130b in the type 2 diabetes mellitus group were significantly decreased, gradually with the increases of UACR. The level of serum miR-130b was inversely correlated with blood urea nitrogen （ r = -0. 295, P〈 0.05 ）, serum ereatinine （ r = - 0.316, P〈 O. 05 ）, UACR （ r = - 0. 463, P〈 O. 05 ）, but positively related to the estimated glomerular filtration rate （ r = 0. 367, P〈0.01 ）. The level of serum miR-130b was also negatively correlated to homeostasis model assessment for insulin resistance, triglyceride, low density lipoprotein-cholesterol, TNF-a, and TGF-β1 （ r=-0. 257, -0. 345, -0. 242, -0. 562, -0. 622, all P〈0.01 ）. The present study indicates that serum miR-130b might be a potential new biomarker for early diagnosis of diabetic nephropathy. Serum miR-130b might be involved in the pathogenesis of diabetic nephropathy.