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人血清中miR-130b水平的变化及其与糖尿病肾病严重程度的相关性。

The changes in miR-130b levels in human serum and the correlation with the severity of diabetic nephropathy.

作者信息

Lv Chuan, Zhou Yue-Hong, Wu Can, Shao Ying, Lu Can-Lu, Wang Qiu-Yue

机构信息

Department of Endocrinology, the First Hospital Affiliated to China Medical University, Shenyang, Liaoning, 110001, China.

Division of Endocrinology, Shenyang No. 8 Hospital, Shenyang, Liaoning, 110024, China.

出版信息

Diabetes Metab Res Rev. 2015 Oct;31(7):717-24. doi: 10.1002/dmrr.2659. Epub 2015 Jun 25.

Abstract

BACKGROUND

Circulating microRNA 130b has been closely associated with multiple diseases in humans such as cancer, obesity and diabetes mellitus. This study evaluates the correlation between serum miR-130b and the severity of diabetic nephropathy evaluated by measurement of albuminuria.

METHODS

Three hundred twenty-seven patients with type 2 diabetes mellitus (T2DM) were divided into three groups: normoalbuminuria group [diabetes mellitus, urinary albumin to creatinine ratio (UACR) < 30 mg/g, n = 137], microalbuminuria group (DN1, UACR 30-300 mg/g, n = 122) and macroalbuminuria group (DN2, UACR > 300 mg/g, n = 68). The levels of serum miR-130b were validated by real-time polymerase chain reaction. Serum transforming growth factor β1 (TGF-β1), hypoxia inducible factor 1α (HIF-1α) and fibronectin were determined by enzyme-linked immunosorbent assay.

RESULTS

Compared with control, serum miR-130b levels were significantly decreased in T2DM patients and further decreased in the patients of diabetes mellitus, DN1 and DN2 groups (p < 0.001). Furthermore, age-adjusted and sex-adjusted regression analyses showed that decreased level of serum miR-130b, increased levels of glycated haemoglobin (HbA1c ), homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride (TG), low-density lipoprotein (LDL), serum creatinine, blood urea nitrogen (BUN), TGF-β1, HIF-1α and fibronectin were significantly correlated with UACR (p < 0.05). In addition, serum miR-130b levels were inversely correlated with HbA1c , HOMA-IR, TG, LDL, BUN, TGF-β1, HIF-1α and FN (p < 0.05).

CONCLUSION

Our findings suggest that serum miR-130b may be a new biomarker for the early diagnosis of DN in T2DM. Circulating miR-130b may possibly be involved in the pathological mechanism of DN, such as lipid metabolic disorders, oxidative stress, extracellular matrix deposition and renal fibrosis.

摘要

背景

循环中的微小RNA 130b与人类多种疾病密切相关,如癌症、肥胖症和糖尿病。本研究通过测量蛋白尿来评估血清miR - 130b与糖尿病肾病严重程度之间的相关性。

方法

将327例2型糖尿病(T2DM)患者分为三组:正常白蛋白尿组[糖尿病,尿白蛋白与肌酐比值(UACR)<30 mg/g,n = 137]、微量白蛋白尿组(DN1,UACR 30 - 300 mg/g,n = 122)和大量白蛋白尿组(DN2,UACR>300 mg/g,n = 68)。通过实时聚合酶链反应验证血清miR - 130b水平。采用酶联免疫吸附测定法测定血清转化生长因子β1(TGF -β1)、缺氧诱导因子1α(HIF - 1α)和纤连蛋白。

结果

与对照组相比,T2DM患者血清miR - 130b水平显著降低,糖尿病组、DN1组和DN2组患者血清miR - 130b水平进一步降低(p<0.001)。此外,经年龄和性别校正的回归分析表明,血清miR - 130b水平降低、糖化血红蛋白(HbA1c)水平升高、胰岛素抵抗稳态模型评估(HOMA - IR)升高、甘油三酯(TG)升高、低密度脂蛋白(LDL)升高、血清肌酐升高、血尿素氮(BUN)升高、TGF -β1升高以及HIF - 1α和纤连蛋白升高均与UACR显著相关(p<0.05)。此外,血清miR - 130b水平与HbA1c、HOMA - IR、TG、LDL、BUN、TGF -β1、HIF - 1α和纤连蛋白呈负相关(p<0.05)。

结论

我们的研究结果表明,血清miR - 130b可能是T2DM患者早期诊断糖尿病肾病的一种新生物标志物。循环miR - 130b可能参与糖尿病肾病的病理机制,如脂质代谢紊乱、氧化应激、细胞外基质沉积和肾纤维化。

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