2型糖尿病不同尿白蛋白排泄率患者血清微小RNA-124-3p与沉默信息调节因子1水平及其相关性  

Correlation between serum microRNA-124-3p and silent information regulator 1 levels in type 2 diabetic patients with different stages of diabetic kidney disease

作　　者：邵滢[1] 任慧雯[1] 吴灿[1] 吕川[1] 安丽[1] 王秋月[1] 

机构地区：[1]中国医科大学附属第一医院内分泌科,沈阳110001

出　　处：《中华糖尿病杂志》2016年第8期483-488,共6页CHINESE JOURNAL OF DIABETES MELLITUS

基　　金：辽宁省高等学校“高端人才队伍建设工程”项目（2014-187）

摘　　要：目的探讨2型糖尿病（T2DM）不同尿白蛋白排泄率患者血清微小RNA-124-3p（Mir-124-3p）与沉默信息调节因子1（Sirt1）水平及其相关性。方法将2013年9月至2015年9月508例T2DM患者根据尿蛋白排泄率（尿白蛋白／尿肌酐，ACR）分为正常蛋白尿组（D1组193例）、微量蛋白尿组（D2组175例）、临床蛋白尿组（D3组140例）。随机选择性别、年龄、体质指数（BMI）与病例组匹配的我院健康体检者211名作为正常对照组（C组）。采用实时聚合酶链反应（RT—PCR）法检测各组血清Mir-124—3p，采用酶联免疫吸附实验fELISA）法检测血清Sirtl、低氧诱导因子1α（HIF-1α）、肿瘤坏死因子α（TNF-α）和纤维黏连蛋白（FN）水平。采用单因素方差分析、Pearson相关分析及多元逐步回归分析对所得数据进行统计学分析。结果单因素方差分析发现T2DM患者血清Mir．124．3p水平[2．85（2．78-2．92）ng／mg]显著高于对照组[0．91（0．87-0．95）ng／mg]，且随着尿蛋白排泄率增加，分别在D1、D2、D3组逐渐升高（F=1348．7，P〈0．001）。与对照组相比，T2DM患者血清Sirtl水平显著降低，并在D1、D2、D3组逐渐降低（F=44．5，P〈0．001）。Pearson相关分析发现Ln（ACR）与年龄、糖尿病病程、空腹血糖、空腹胰岛素、稳态模型胰岛素抵抗指数（HOMA—IR）、糖化血红蛋白、低密度脂蛋白胆固醇、总胆固醇（Tc）、甘油三酯（TG）、血肌酐（Scr）、血尿素氮（BUN）、尿酸（uA）、HIF-1α、Mir-124—3p、TNF-α、FN呈正相关（r=0．105—0．813，均P〈0．05），与高密度脂蛋白胆固醇、Sirtl呈负相关（r=-0．113、0．360，均P〈0．05）。多元逐步回归分析发现Mir-124．3p、FN、TNF-α、HIF-1α、TC、糖尿病病程、BUN、Sirtl、UA以及年龄是影响Ln（ACR）的主要因素，其方程为：Ln（ACR）=-3．617＋1．005×Mir-124-3p＋0．002×FN＋0．014×TNF-α＋0．035×HIF-Objective To investigate changes of serum microRNA（Mir）-124-3p and silent information regulator l（Sirtl） levels in type 2 diabetic patients with different stages of diabetic nephropathy. Methods Total of 508 cases with type 2 diabetes treated from September 2013 to September 2015 were divided into three groups according to the urinary albumin excretion rate： normoalbuminuric（D1, n=193）, microalbuminuric（D2, n=175）, macroalbuminuric group（D3, n=140）. Serum levels of Mir-124-3p were validated by real-time polymerase chain reaction. Serum Sirtl, hypoxia-inducible factor-1α（HIF-1α, tumor necrosis factor-α（TNF-α） and fibronectin（FN） were determined by enzyme-linked immunosorbent assay （ELISA）. One-way analysis of variance, Pearson correlation and multiple stepwise regression analysis were used for statistical analysis. Results The level of serum Mir-124-3p in type 2 diabetic patients （2.85 （2.78-2.92）ng/mg） was significantly higher than that in control group （0.91（0.87-0.95）ng/mg）, and with the increase of urinary albumin excretion rate, the levels of serum Mir-124-3p in group D 1, D2 and D3 increased gradually（F=1348.7, P〈0.001）. Compared with control, serum Sirtl level decreased significantly in type 2 diabetic patients and decreased gradually in patients of D 1, D2 and D3 groups（F=44.5, P〈0.001）. According to Pearson correlation analysis, age, diabetes duration, fasting plasma glucose, fasting insulin, homeostasis model assessment for insulin resistance（HOMA-IR）, glycated hemoglobin A1c（HbA1c）, low-density lipoprotein-cholesterol（LDL-C）, total cholesterol（TC）, triglyceride（TG）, serum creatinine（Scr）, blood urea nitrogen（BUN）, uric acid（UA）, HIF-1α, Mir-124-3p, FN and TNF-α were positively correlated with Ln（ACR） （r=0.105-0.813, P〈0.05）; high-density lipoprotein-cholesterol（HDL-C） and Sirtl were negatively correlated with Ln（ACR）（r=-0.113,-0.360, both P〈0.05）. According to multiple stepwise

关 键 词：糖尿病 2型 糖尿病肾病 微小RNA-124-3p 沉默信息调节因子1 低氧诱导 因子1α 

分 类 号：R587.2[医药卫生—内分泌]